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5-1-1935

Problem of pulmonary : report of thirty nine cases

Richard Birge University of Nebraska Medical Center

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Recommended Citation Birge, Richard, "Problem of : report of thirty nine cases" (1935). MD Theses. 565. https://digitalcommons.unmc.edu/mdtheses/565

This Thesis is brought to you for free and open access by the Special Collections at DigitalCommons@UNMC. It has been accepted for inclusion in MD Theses by an authorized administrator of DigitalCommons@UNMC. For more information, please contact [email protected]. Report of Thirty-nine Ca•••

Richard Birge

Senior Thesie

tJniversit7 of •ebraslca College of Medicine Omaha, •ebraska 1935 TA:BLB OJ OOl'!lftS

Page

I. IB'J!IODUC!CllY ••••••••••••••••••••••••••••••••••••••••••••••••••• 1 II. THE OLIBICAL CAO

.A.. S711>toma ••••••••••••••••••••••••••••••••••••••••••••••••••• 3 :e. Diagnoa1a •••••••••••••••••••••••••••••••••••••••••••••••••• ., III. MORBID .AD.!.OMY

.A.. '1'he J.utopay :rindinga ••••••••••••••••••••••••••••••••••••••• 10 B. The fhroabue ••••••••••••••••••••••••••••••••••••••••••••••• 12 c. The Bm'bolua...... 15 D. The Pathological Ja.clr&round •••••••••••••••••••••••••••••••• 17 1. PlQ"aical and Mec:hanical Jactors Concerned in !rhrombosia and Embolism...... 18 2. Biochemical J'actora Concerned. ill !hromboaia 8lld .,.boliam. •••••••••••••••••••••••••••• 22 3. The Role of Infection...... 29 IT. ml INCIDDCE OF POLMOIWlY mmotIS.-CONSIDIRA!IOB OJ' CAD BISTOllDS

.A.. General Conaiderationa ••••••••••••••••••••••••••••••••••••• 33 B. Relation of .Age to PulmoDa17 Bmboliam •••••••••••••••••••• ". 34 C. Relation of Sex to Pulmna17 Jlmboliam...... 35 D. Relation of Race to Palmonar7 lmboliam. •••••••••••••••••••• 35 •· !he Sourcea of Pa.lm:>na.ry Em.boll •••••••••••••••••••••••••••• 35 J'. Relation of PnlmoDa.17 lmboliam to the Pri111a17 Diaeaae. • • • • • 36 G. latal Pulmona.17 Kmbollam ••••••••••••••••••••••••••••••••••• 38 K. Postoperative and Poat Partum Palmnar;r &aboliam. •••••• •••• 41 I. Relation of Diaeaae to Pul.moDar1 Jlmboliam...... • • . • • 41 J. Paln>na?'7 :lm'boliem Complicating Septic !rhromboais •••••••••• 45 x. Relation of Theraw to Pulmona17 lmboliam...... • • • • • • • • 45 L. Presentation of Case Kiatoriea •••••••••••••••••••••••••••••• 46 V. 1IOTIS 01 'fBEB.APltJSIS ••••••••••••••••••••••••••••••••••••••••••• 92

VI. SUMYA.ttt •••••••••••••••••••••••••••••••••••••••••••••••••••••••• 95 TII. BIBLIOCIRlPBt ••••••••••••••••••••••••••••••••••••••••••••••••••• 96

..... ,_

4806?6 THE PROBLIM OF PULMONARY EMBOLISM: Report of Thirt7-nine Cases

INTRODUCTORY

The question of pulmoDa.17 embolism ha.a become quite recentl7 one of m:>re than usual interest at the University Hospital. In a period of leas than four months, during the latter part of 1934, six cases of ~l pulmonary embolism came to autopsy. There had been no caaes of fatal pulmonary embolism during the first eight months of 1934, but one case in 1933, and two in 1932.

A. review of these cases revealed. nothing which might explain the increased incidence of fatal pulm:>nar7 embolism. It was, however, known to the writer that a quite large percentage of autopsies show evidence of pulmonary embolism, when both fatal and non-fatal cases are considered. It was recalled that, since the occurrence of pulmonary embolism depend.a upon the formation of priiary thrombi in the systemic venous ayatem or in the right heart, the amount of which might break loose and reach the pulm:>nary arterial system through the blood stream would be the essential factor determining the outcome of a given case. It seemed that one might consider the occurrence of as the fundamental pathological chaDge in these cases, and tlle embolic involvement of the l'UJlgs as incidental or accidental. It this conception were proper, leas significance C011ld be attached to an increase in the occurrence of fatal pulm>nary emboliam over a short period of time. The important problem PROBLEM OF PULMONARY EMBOLISM 2 would be to determine whether the increase in fatal cases was actually accompanied by an increase in total cases of pulmonary- embolism, or whether the increaae depended only- upon the fact that, in a small group of' cases, larger than usual emboli had gained access to the pulmonaey . University Hospital records for a three-year period ending December 31, 1934 reveal a smaller n'tllllber of pulmonal7 emboli found at post-mortem examination during 1934 than during either of the two preceding years, although pulmonary embolism aa the primaey cause of death was more frequent in 1934. In the three-79ar period 309 autopsies were performed. In thirty­ nine, the post-mortem diagnosis of pulmonary embolism or pulmonal7 infarction was ma.de, and in nine, pulmonaey embolism was found to be the primary cause of death. !he percentage incidsnce was 12.6 per cent for total cases show­ ing pulmonary embolism or infarction, and 2. 9 per cent for cases of fatal pulmonaey embolism. Thia series of cases is too small for a critical atu.c!T of the incidence of pulmonary embolism and of the more important factors related to ita occurrence. It is of interest because it demonstrates the total incidence of pulmonary embolism cases at the University Hospital to be comparable to that of other hospitals and clinics where much larger aeries have been acC'Ulll'l1l.ated, and, most important of all, because 1t demonstrates no increase in total pulmonary embolism cases in 1934 corresponding to the increase in fatal pulmonary embolism cases during that -rear. The thirty-nine autopsy cases seen in the University Hospital during

1932, 1933, and 1934 are S'UDllllB.l"ized, and their essential features, in rela• Uon to the comoon finding of evidence of pulmonary embolism, are discuase4 in the following pages. THE CLINIC.AL CASE

Symptoms

Pulmonaey embolism may be so insignificant as to produce no symptoms

whatsoever, or so massive as to result 1n death in a few minutes or hours. It occurs most frequently in middle-aged or elderly patients following some . -1 minor exertion to which the patient has been ilnaccuatomed, as, for example,

getting out of bed. The chief symptoms are ~ea, cyanosis or pallor, often precordial or substernal pain, sweating and other evidences of , and eometimee anxiety with fear of impending disaster. The severity of the symptoms depends largel.7 on the size and number of emboli and the resultant degree of embarrassment of the pulmonary circulation•

.A. sudden and unexpected onset of s;vmptoDB is characteristic. Death ensues within a short time if the common pul:mnary is occluded or if multiple small emboli occlude a sufficient amount of the pulmoJla17 arterial system. However, death is not immediate. Of the nine Un1vers1t7 Hospital cases (pages 48 to 58) in which plil.monar;y embolism was the immediate cause of death, the shortest period intervening between onset of &1JU.Ptoms and exitus was seven minutes in case 4 (page 51), and the longest period was two hours and twenty-five minutes in case 5 (page 53) •

.A.t necropsy -.sive emboli were found in the common pul:mnar;v arterT, but, because of the length of survival, after the onaet of sYq>toms, it is apparent that occlusion could not have been complete in 8J17 case. In this respect the experimental work of Haggart and Walker (26) on laboratory animals is of passing interest. They found that until from 52 to 66 per cent of the pulm:>nar;v circulation is cut off there ia no significant variation of the circulatory condition of an animal, and that the end-point PRO:BLEM OF PULMOHA.RY EMBOLISM 4

(52 to 66 per cent) is sharply defined, and circulato1"7 collapse is pre­

cipitated by minute increases in pulmona.r;y arterial obstruction be7ond the end-point.

Relativel7 small pulmonaey emboli DlaY' cause sudden, sharp pain in the

chest, producing signa of consolidation and perhaps a friction rub. The

teDg?erature rises, and the leucocyte count is usua.ll;r found to be moderatel;r

increased. The respiration is shallow and rapid, due to the pain produced

by deep breathing. A.fter a abort time cough 11!81' develop with expectoration

of blood-streaked aputum. A.fter a few days the symptoms 11181' resolve and

the patient coupletel7 recover. Case 14 (page 63), for example, complained

on .A.pril 30, 1932 of sudden onset of pain, exaggerated by deep breathing,

over the region of the liver; there was heDDptyt1is in small amounts for

three days; and ph1's1cal examination revealed an area of dullness over the

right lower lobe. The symptoms of pulmonar;r embolism cleared up and the

patient died a week later, a cardiac death. Necrops;r revealed a large intarct in the right lower lobe.

There may be multiple and smaller emboli, followed by larger onea.

Blood-t i?J88d sputum is usually seen after the lodgement of the earlier emboli, and a patient 1118.7 have apparentl7 recovered when the proceas ia repeated. On August 10, 1934, case 4 (page 51) complained of rather sharp pains over the precordium with only slight difficult7 in breathing. On

.A.'1lgll8t 17 the patient had a severe pain in the right lower chest with radiation to the shoulder. Coarae rales were fo'UJld in the lower right cheat with diminished breath sound.a. J'ollowing this occurrence the patient covgb.ed considerably, with production of some blood-streaked sputum. On

.A.'Ug\lat 26 the patient had been sitting up in bed, suddenly screamed, collapsed, and died about seven minutes later. PROBLEM OF PULMOlfA:RY EMBOLISM 5

.A single 118Ss1ve pulDX>n&.ey' embolism JDe1' occur. with death resulting

in a short time. .A cholec7stectorq and appendectorq had been performed on

case 5 (page 53) on September 10, 1934. The patient progressed well until

the fifth postoperative day' when she suddenly sat up in bed, breathing rap­

id.17 and showing considerable cyanosis. She complained of no pain. She

was given morphine, caffeine aodio-benzoate, and digalen, but she died two

bours and twenty-five minutes after the onset of the s1111Ptoma. .A.t autopsy a single ante-mrtem thrombus was found in the common pulmo?l81'7 arteey.

It was sixt7 centimeters in length and of pra.cticall7 uniform diameter,

about one centimeter. There were no thrombi in the branches of the pul­ monar7 arteries, and there were no infarcts in the lungs.

Infected ante-mortem blood clots JDe1' reach the pulmonar;y arterial system. They are usually mltiple and small, and give rise to amall in­ farcts which soon assume the characteristics of ordinary meta.static lUJlg abscesses. Seven of the cases in this series (cases 27 to 33 inclusive, pages 79 to 85) showed this t)"p8 of lung patholoa. In all of the seven cases the primary thrombi were associated with definitel7 inflaD111&tory processes. Since pol.monaey emboli in these cases were small and caused little pulmonary circulatory embarrassment, they produced no demonstrable clinical symptomatology except that referable to the inflammatory processes.

On the other hand, a pulmonar;y infarct of considerable size 11187 under­ go secondary infection and degeneration. Case 36 (page 88) showed at autopsy gangrene, associated with pulmo118.?7 thrombosis, of the lower lobe of the left lung. There was a primar;y pelvic thromboais which showed no evidence of being infected, and it may therefore be concluded that the gangrenous process in the lung was associated with secondarT bacterial

invasion. Dr. J. P. Tollman, Pathologist at the University- Hospital, PROBLEM OF PULMONARY EMBOLISM 6

confirms this interpretation in his report of the case, saying: •This is interpreted as beil'lg a pelvic thrombosis. Some of these thrombi became loosened and caused infarction of the left lower lobe of the lung. It subsequentl;y became gangrenous.• In such cases the s;ymptomatolog;y is that

of the usual non-fatal case of pulmona.17 embolism, with the symptoms related to the gangrenoua change in the lung developing in the course of a few days.

In BUJllDation of the symptomatology of pulmonar;y embolism, it Dl8.1' be

well to quote Churchill ( 18), who says: •One of the beat expositions of the of pulmonary embolism. is to be found in the paper of Giertz and Orafoord, based on a statistical anal;yais of the clinical picture presented by twent;y-aeYen patients. In twenty-three instances the condition was correctl;y diagnosed before death. '?he S1JD.Ptoms observed were, in order

of frequene;y, as follows: sudden onset of symptoms without any warning: high, soft, imperceptible ; marked pallor; unconsciousness; slight cyanosis; craving for air; d7apnea; altered respiration, superficial or

deep; snatching or groaning; feeling of oppression, dread, anxiety, rest­ lessness; pain, or stitch in chest, uauall;y over precordium; •shock•, cold perspiration; pulsations in of neck (the authors remark that this syn:g;>tom is probabl;y more frequent than was noted in the brief accounts available); waving arms about, wanting to get up. Violent vomiting, atrabismus, dilated pupils, giddiness, and yawning also occaaiona.117 occur.

~he aymptomatolC>g1 is sumnarized as follows: 'In most instances it (massive pulmonary embolism) comes like a bolt from the blue with tn>ical symptoms of which the most frequent are intensive pallor, loss of pulse and conscious­ ness. Common &1JD.Ptoms are also oppression, craving for air, and a mild c7anosis with a ty:pical venous pulsation above the claviclea. 1 " PROBLEM OF PULMONARY EMBOLISM. 7

Diagnosis Pulmonary embolism is a much more frequent occurrence than is genera1}7 recognized. University Hospital autopsy reports over a three-year period reveal a total incidence of 12.6 per cent of pulJD:)nary embolism cases in total autopsies performed. Belt (12) emphasizes in a recent paper that pulmonary embolism is much comm:>ner than it is usually considered to be.

Re states: "Usually regarded as a postoperative event of relatively rare occurrence it proves, on the contrary to be a cormrnn autopsy finding, more often associated with medical than with surgical cases. The frequency with which it may be uncovered at autopsy is surprisingly high, as many pathol­

ogists have already pointed out (Lubarsh, J'abr, Henderson, Singer, Wertheimer 1

Dietrich, Benda., Ceelen, .A.xhausen, Putnoky, and Farkas). On our own service, under the direction of Prof. Oskar Klotz, we have demonstrated pulmonary emboli in about ten per cent of our routine autopsies." Once the frequency of pulmonary embolism is recognized and the con­ dition thought of in making a differential diagnosis, and once it is realized that pulmonary embolism occurs in medical as well as postoperative surgical cases, the diagnosis of pulmonary embolism will be made by the clinician in a large number of cases previously diagnosed only at autopsy. In this connection Bunn (16), in discussion of differentiation of pneumonia from pul!IX>nary embolism, says that the chief error in a number of cases which were provisionally diagnosed as pneumonia was the failure to consider both pneumonia and pulmonary embolism as possibilities.

Hamburger and Saphir (28) also suggest that 1 in cases of sudden severe dyspnea, unexpected death following some slight exertion, acute severe right­ sided , unexplained sudden death, consider, at least, pulmonary embolism either alone or in association with . .A.s part of such consideration look particularly for the possible thrombotic source PRO:BLEM OF PULMONARY EMBOLISM 8

of such embotic and evaluate the degree of c7anosia, increased right heart dullness, sud.den engorgement of the liver, as fitting into the picture of

acute right heart failure from pulm>naey obstruction.• The authors admit

that the differential diagnosis between pulm>nary embolism and coronary

thrombosis may be difficult, but reiterate: "If the possibility of pul­ monaey embolism is more frequently borne in mind as 'complicating or simulating• coronary thrombosis, •e feel the percentage of correct diag­ noses will be proportionately higher.• Besides pneumonia and coronary thrombosis, the chief conditions, according to Lord (17), with which pulmonary embolism may be confused are postoperative shock, postoperathe concealed internal hemorrhage, and acute pn8UDl>thorax.

The fundamental phenomenon in cases of piil.monary embolism is the thrombosis occlll"ring either in the systemic venous system or in the right heart. Clinically, however, evidence of a thrombotic process is usually not elicited prior to the onset of symptoms of embolic manifestations, excepting in cases, such as a lateral sinua thrombosis extending from a mastoid infection, which are en a septic basis. In the group of thirt7- nine cases, there were seven cases of this frankly septic thrombotic tyPe ' (cases 27 to 33 inclusive, pages ?9 to 85). Only two other cases (cases 8 and 18, pages 56 and 6'7) showed definite clinical evidence of thrombo­ developing as a prem>nition of the embolism to follow. McCartney ( 45) sqs in this respect: "Pulmonary embolism results from thrombosis, but apparently most often occurs when symptoms of thrombosis are absent. Conner ( 19) sqs, 'There is reason to believe that the characteristic local signs of appear only after the occlusion of the has been complete and after more or less periphlebitic PROBLEM OF PULMONARY EMBOLISM 9

has been added.• This may explain why' embolism occurs when

signs of thrombophlebitis are absent rather than in cases of :frank phlebitis.

A thrombus completely occluding the vessel would, perhaps not become de­

tached so easily as would the thrombus floating in the blood stream and attached only over a relatively small area.•

Consequently, if one is to predict the possible occurrence of a pul­

monary embolism in a clinical case, one D1t1St look elsewhere than for evidence of thrombophlebitis. According to Rosenthal ( 61) the two most important factors in the for-.tion of thrombi. outside of colloidal, chemical. or ph1'aical changes of the blood, are in order of importance,

heart and vessel changes, and infectious proceaaea. !hie observation is veey definitely borne out by tbe group of cases under consideration. Twent7- one were definitely associated with circulatory failure on a cardiac basis, and at least eight were associated with infectious processes involving the

veins or the endocardium. These problems •111 be discussed in considerable

detail below; it is only essential to emphasize here tbat, altbo"Ugh JllBD7

cases of pul.monarr embolism are unpredictable, venous circulatory stasis and septic thrombophlebitis are tbs chief forerunners of pul.mo:naey embolic accident a. MORBID ANA.TOM?

The Autopsy Findings McCartney (45) describes the chief post-mortem findings in a case of fatal pulmonary embolism so adequately and concisely that it may be well to cite the description:

1 Cyanosis, which mt:cy" have been pronounced at the time of death, usually ha.a disappeared by the time the necropsy is performed. · Edema of the subcutaneous tissues mq or Jr1a7 not be deDl>nstrable. Usually the right ventricle and auricle are found distended. If the heart is removed before the pulmna.ry artery and its two main branches a~ examined, the embolus mq be overlooked. The embolua may be found obstructing the right or left pulmonary artery, or riding over the bifurcation, filling the pulmonary artery, or even extending back into the right ventricle.

The embolus mq be made up of Dia.DY pieces of blood clot, or be a long folded or coiled mass. The external surface of such an embolus usually shows fine corrugations (the lines of Zahn) and has a red, white, or mottled appearance. If, instead of a single large embolus, there has been a shower of small emboli, these will be found in the smaller branches of the pulmonary arteries. Infarcts are not usually present.•

B'.e contimies: "In delqed death the emboli J11a7 propagate in the pulmonary arteries and become adherent, so that it is sometimes difficult to distinguish between embolism and primary thrombosis of the pulmonary artery •. The lungs mq be normal or show edema and congestion. In slow deaths infarcts, bronchopneumonia, or in the case of infected emboli, ab­ scesses mq be present. The liver, spleen, and kidneys show acute passive congestion.• PROBLEM or PULMONARY IMl30LISM 11

It is apparent, therefore, that the pathological findings in the pul.DX>nar7 arterial s7stem are the ante-mortem clots occluding the s7stem and the evidences of secondary changes in the heart, lungs. and other or­ gans. The other important findings relate to the underlying pathological conditions which JDa7 suggest an explanation for the occurrence of embolism.

The pathologist consequently' searches as carefully- as he may for the throm­ bus or the former site of the thrombus. and also attempts to determine evidence of local trauma, infection, circulator;y failure, and other factors which 1181' explain the formation of the thrombus.

The source of the embolus in DlaJl1' cases is not found. McCartney ( 45) points out that this is often because a sufficiently- thorough search can not be made. :Belt (11) also points out that often enough one is able to demon.strate pulmonar;y emboli, but is unable to find their point of origin, and that on the other hand one· JIS:r find an undiagnosed , especially- in the leg and pelvic veins, from which no emboli have arisen. Since complete can rarely be made at autopsy, Belt suggests that a thrombus will often be dislodged from a femoral vein if the legs be elevated and massaged, but that failure does not prove a thrombus is not present. It is also not infrequentl7 the case that a thrombus forming, for example, in one of the external iliac veins, may, when the embolus forms, be completely dislodged, leaving at the former site of the thrombus a smooth vesse~ wall showing no evident pathological alteration. PROBLEM OF PULMONARY EMBOLISM 12

The Thrombus

"Coagulation of blood in the vessels after death or in the tissues or in the test tube presents· a fundamental structural difference from thrombosis intra vi tem•, according to :Belt ( il) who points out that the chief constit.uent of the former is , while that of the latter is platelets. Re continues: 11'l'his structural difference is reflected in the naked eJ'e appearances. .Ante-mortem clot tends to be firmer, less elastic, dry, brittle, and rough. If the clot be adherent to the lining of the vessel or if it be of a friable consistency, there can be no doubt as to its ante-mortem origin. Not infrequently one must rely on still other criteria. There is a characteristic laminated structure, n:ade up of grayish 1.a7ers interlarded with red; this feature is lacking in the post•

:mrtem clot though it IDB1' be aim.lated by the haphazard admisture of white and red elements. Lastly, the ante-mortem clot is often characterized by a rippling of its surface with fine greyish "drifts", like the wavy ribbing of a san~ beach, the so-called lines of Zahn, made up of platelets. 'l'his rippling al•STs means that the clot was laid down in a moving blood stream; sometimes, however, the phenomenon may be observed on the surface of agonal clots which have formed during the last period of life and which must be distinguished from true ante-mortem clots.

"It is rarely necessary to employ the microscope to distinguish throm­ bus from post-mrtem clot. Microscopicall7, the post-mortem clot is made up largely of blood cells (red and white) n:atted together with frail strand.a of fibrin. There l'DB1' be small clusters of platelets. The ante-mortem clot on the other hand has a large platelet coun·fi: platelets form the basis of the coagulum, enmeshing variable quantities of cellular elements. If one PllOELEM OF PULMONARY EMBOLISM 13 can detect with the microscope 8ZJ7 sign of organization of the clot, the ingrowth of fibroblasts, this is, of course, definite evidence of ante­ mortem formation.•

Romans ( 3$ has described in considerable detail some of the more com­ mon and important forms of venous thrombosis of the lower extremities and pelvis, which are the two U8'U8l sources of pulmona?7 emboli, excepting the septic forms which arise from a site of s'OppUl'ation. '?hrombotic processes of the lower extremities he has classified into four chief t1}>8et super­ ficial thrombosis, associated with varicosities of the legs; deep thrombosis of the lower legs; phlegmasia alba dolens; and phlebitis migrans. He sqa of the first form: •Thrombophlebitis in is, obTiousl7, re­ lated to the unhealth;y state of the vein's wall. Whether a 'latent t in­ fection is present is imna.terial. The fibrosis and distortion, not to speak of the effect of sud.den oTerstretching on particular occasions, al"8 quite enough to account for thrombus formation. The leg as a whole is not swollen, the reaction being confined to the neighborhood of the varicose vein. The clot 1e usuall;y quite well fixed, as one might expect, and is rarel7 detached, though I have, on one occasion, divided a thrombosed varicose vein at the groin because of repeated pulmona17 infarction. "

Pate7 ( 53) believes that varicose veins are a very rare source of emboli.

Rabinowitz and Holzman ( 57) are of the opinion that ID8ll1' pulmonary emboli have their source from the deep veins of the legs and that at necropsy the lesions are overlooked because the bulk of the naas has broken loose and lod&ed in the pulmonary artery, while onl7 in the small veins of the calf and leg will the remnants of the original thrombus be found. Homans considers this t7.P8 of thrombosis to be of great etiological significance, PRO:BLEM OJ' PULMONARY EMBOLISM 14

and describes the pathological findings and associated clinical syndrome:

"A local, deep thrombosis in the lower leg begins with a variable but, on the whole, a noderate amount of discomfort in the calf, swelling of the ankle, and blueness of the foot; signs which are rather promptly ma.de to disappear upon rest in bed, but which recur over and over again upon attempting the use of the leg. It is hard to believe that, as a result

of elevation for only a day or two, the leg, actually the seat of the ex­ tensive deep thrombosis, can take on so nearly, or completely, normal an

appearance. Yet autopsy in the fatal cases has shown a remarkable wide­ spread, persistent thrombosis in the great vessels among the muscles of the calf. In each case, the femoral vein was actually unobstructed and the

cause of the fatality was the detachment of a considerable fra.gment of an enormously long, insecure thrombus which had been waving, as it were in the current • 11 Phlegma.sia alba dolens is primarily a pelvic process, though the throm­

bosis may extend for a long Wa'J' peripherally. Homans says of this form:

11 E:xplorations by the writer have shown that in many instances there is an active exuda.tive reaction about the external iliac artery and vein (the coumon iliac or even the vena cava in some cases). The great vein is solid­

ly obstructed by a firm thrombus. The whole leg, not just the lower portion is swollen. In some instances, there is evidence of arterial spasm result­ ing in some degre1' of ischemia. In all cases, going to bed has little ef­ fect upon the disease, the swelling persisting in even the mild.est cases for

a week or ten days and occasionally for many months. There is often tender­ ness over the deep vessels at the groin and over the femoral canal. Some­ times the saphenous vein is noticeably involved. In other instances, it is seen to be dilated, particularly in the groin, as if it were acting as a PROBLEM OF PULMONARY lllMBOLISM 15

collateral. lmbolism, considering the frequency of the disease, is un­

common, a matter which Dlfl1' be related to what seems to me to be the usual source of the process, that is, an inflammatory reaction within the arterio­

venous sheath. !his may give an adhesiveness to the thrombus which is ab­ aent in the tY,pe of disease which forms the subject of this paper (deep thrombosis of the lower legs). In this connection, Cruveilhier, who des­

cribed deep, iliac phlebitis so Dl8Jl1' years ago, said that he had never seen inflammation within the vein, but alw81'S in its wall." Thrombophlebitis of the migrating type, that is, the phlebitis migrans so commonly associated with thromboa.ngiitis obliterans and occasion­ ally seen as an independent disease, is a local superficial process, an inf'lanmatory lesion which never leads to extensive thrombosis or swelling of the affected limb, accordi:og to Homans.

The Em.bolus

It ma:y be at times a puzzling problem to determine whether an attached ante-mortem blood clot found in a pulmonary artery is a. primary thrombus or an embolus which has become secondarily attached. In the study' of the group of cases under consideration, a large number were found to show attached ante-mortem clots, some of which it would probably be impossible to designate with absolute certainty as embolic. Belt (11) has noted this

difficulty, and has set down some of the essential findings which may aid

in making the differentiation. 11.l thrombus of the pulmonar,y artery•, he finds, "starts usually as a mural plaque-like clot with sessile base and shelving margins, firmly adherent to the in.time.. It DIB7 grow and com­ pletel)' occlude the vessel, but it alWSl'S conforms to the size and shape

of the pulmonary artery, whereas an embolus, on the other hand, having been PROBLEM Ol!' PULMONARY EMBOLISM 16

cast in the shape of some other vessels 11183' bet~ its foreign origin in a number of ~·· It 11181' be riding upon a bifurcation or coiled upon

itself, and this is particular]Jr true of the long cylindrical emboli which are usua.117 ca'Ugbt in the main trunk of the pulm:>nary arteey. An embolus

is 11kel7 to have a number of small twigs attached to it which represent the moulds of suell tributaries of the vein in which the thrombus was formed. An embolus 1118.7 have a ragged or •fractured' end which will in­ dicate that the clot has been broken off from a larger ma.BB in some other part of the boey."

A further difficulty, howeTer, in making the differentiation between pulmonary- emboli and autochthonous thrombi liea in the fact that small emboli ~ by accretion increase in size and the prima.17 character of the process be lllB.sked. Xampmeier ( 38) finds that there are two nain causes of pulmonary thrombosis- of the pu.lmnaey artery and embolism.

Atheromata, he suggests, may be primary or of syphilitic origin, but are probabl7 more frequentl7 secondary to fibrosis or emph1'sema of the lu:ng, or to mitral stenesis. Concerning embolism as a cause of pulmnary throm­ boaia he eqa: "It is believed by several authors that embolism occurs in a branch too SD1all to give the characteristic s~toms of pulm:>nar7 em­ bolism with infarction. The small embolus then by accretion develops into a progressing thrombosis extending and involving the main branches of the pulmonaey artery."

Belt (11) a«rees that some cases regarded as thrombosis 11181' have had embolic origin. It has seemed to the writer that pulBDnary arterial throm­ bosis would be an unusual occurrence because of the character of the cir­ culatory mechanism concerned, which is arterial, and because the arteries infrequently show the above-mentioned change& in the walls which Xampmeier PRO:BIAI OF PULMONARY EMBOLISM 17

considers prerequesite to thrombosis. In none of the University Hospital

cases reported was there evidence of pathological change in the walls of the pulmonary arteries sufficient to account for the formation of autoch­

thonous thrombi. The questionable cases. wherein the blood clots found in

the pulmona?'J' arteries are described as thrombi, JDa7. therefore, be con­

sidered to be primarily embolic processes, with seconda17 adherence to the vessel wall and with the addition at times of a certain amount of local clotting by accretion.

The Patbological Background

.A. consideration of the factoraunderlying the occurrence of pulmonary embolism is chie:f'ly a consideration of the broader subject of the causes

of the formation of thrombi from which pulmona.1'7 emboli may originate. Thrombosis is primarily a l>h1'siological process constituting an essential defenae mechanism to the credit of which, says Homans ( 35) , we D11st concede the preservation of the race as it came up through savagery to civiliza• tion. !his defense mechaniam comes into action in response to injury to the blood vessels and tissues by phTsical agents or by chemical, biochemical, or bacterial action. Its initiation appears to be through the action of some vital substance or substances called forth by the injury and variously known as fibrin ferment, early toxins, thromboplastin, and thrombokinase. The known factors in clotting Bancroft, Kugelmaas, and Stanley-Brown ( 4 ) have concisely yet clearly outlined: "When blood is shed the plasma dissociates into substances which yield a clot. Do.ring the patent period of dissociation, antithrombin is precipitated and prothrombin is activated by calcium ions. The resulting thrombin gels soluble fibrinogen into insoluble fibrin.• PROBLIM OF PULMOHA.RY lillmOLISM 18

Normall7, Homans continues, clot formation sufficient for the purpose

of plugging the seTered vessels takes place and then ceases. Why' it ceases is as great a 1Jl1'&tery as wb7 it starts. Such a normal reaction or defense mechaniem becomes pathological b7 its excess, its location, and the surrounding conditions, of which the most important is its intrusion into the centripetal blood stream where it tends to self-propagation until

overtaken by natural limiting forces.

Ph;raical and mecbap.ical factors concerned ,!a thrombosis s4 embolism: Thrombosis has been defined as an intrava.scular clotting during lifetime. The formation of an intraTascular clot during lifetime is a condition which by its very nature presupposes a slowing of the circulation, and in this respect is not different from post-mortem clotting. Venous stasis ia, then, a fundamental pathological alteration which mast take place before a Tenous thrombus will form.

Bunn ( 1$ eupbasizes the importance of venous stasis in stating that;

"Infection, trauma, and alteration of the plcy'siology of blood clotting JJl81' be contrilnl.toey causes, but slowing of the circulation appears to be the one constant factor necessary to permit a vein to be thrombosed."

Rewlet t (33) also speaks of the importance in thrombosis and pulmona?'J' embolism of a slowing of the blood stream, saying: ".A.mong the conditions which faTor the deTelopment of thrombi is a marked slowing of the blood

current. This may be due to a general slowing of the blood stream throughout the bodT (cardiac insufficiency), or it DlS7 be due to some local obstruction to the blood flow. Marked slowing also occurs in certain

portions of the eddies which al1181'B arise when a:q flowing stream passes an obstruction, a bend, or a suddan widening. It is evident, therefore, PROBLEM OF PULMONARY EMBOLISM 19

that thrombus formation is favored particularly in the irregular dilata­ tions of varicose veins, such as occur in the lower limbs and in the pros­ tatic plexus of elderly men. The bend in the fellX)ral veins near Poupart•s ligament, and dilatation in the blood channel which occurs when the blood enters an aneurism or an auricle, play a role in explaining the frequency of thrombi in these locations. Compression of the left iliac vein by the arw terial trunks may account for the well-known frequency of thrombosis in the left as compared with the right lower limb."

Clinical observation also yields confil'Jn9.tion of the theory of the significance of stasis in the formation of venous thrombi. Pigford (55) says that the role of stasis is suggested in those who develop thrombosis during prescribed bed rest. When one recalls the marked shift in the intravascular bed, and the attendent retardation of the blood flow incident­ al to the enforced bed rest, in cardiac, surgical, and obstetrical cases, the possibility of a relationship between stasis and thrombosis is to be considered. :Belt (11) has found that: "In our cases there is a high correlation between circulatory failure and pulmonary embolism-. With Jil8JlY other authors we believe that slowing of the blood flow is probably the roost important factor in predisposing to the development of the dangerous ty-pe of thrombi within the veins."

The IJX)St comoon condition in which there is slowing of the blood flow in the veins is cardiac disease, yet Steuer (66) points out that although the literature abounds with general studies on thrombosis and embolism, the relationship between pulm:>nary obstruction and heart disease ba.s been somewhat neglected. Pigford (56) agrees that thrombosis is mre frequently associated with PROBLEM OF PULMONARY EMBOLISM 19 heart disease than 8.111' other one group, and this observation is in keeping with the findings in the aeries of thirt7-nine Univerait7 Hospital cases under consideration. Pigford continues: •As an accompaniment of acute and subacute , and as a consequence of chronic cardiac valT'l>'t lar disease, coronary arterial disease, and as intramural thrombi associat­ ed with chronic ~cardial insuffieienc7, it aasmnes a position of major importance. The stasis produced in the auricular appendages as a result of a systole in these chambers, probabl7 accounts for the high incidence of thrombi in auricular fibrillation. The m:>st conmon site for thrombi in the aeries of B'arvey and Levine. were the auricles and the tip of the left ventricle, the points of least circulator,- activit7.in the heart cham­ bers.•

Virchow (Rosenthal, 61) was the first to designate in 1884 non­ infectious processes in the causation of thrombi. His conception was that a sluggish circulation (marantic, compressional, dilatational, and traumatic), in addition to various changes in the blood proper, were predisposing factors. This viewpoint is essentially that of many contempora17 students of the subject. The writer has in the preceding pages cited a similar view of Rosenthal'•· Rosenthal (61) in a atud1' of one thousand cases of thrombosis and embolism f'oi:md the incidence highest in individ'llala over fort7-one years of a«e in whom heart disease was present. According to

Steuer (66), the inference would be that stasis of the blood resulting from a failing ~ocardium is responsible for thrombus formation, but he adds:

•1xperimental work, however, has shown that stasis alone, or in association with endothelial injury will not result in thrombus formation. It appears, therefore, that the changes in the blood itself, physical, chemical, and PROBLEM 07 PULMONARY EMBOLISM

colloidal changes are necesaa17 in order that thrombus formation take place."

The latter factors, as well as the possibly essential role of inflammato17

processes, often perhaps non-auppurative, will be considered in succeeding pages.

Mechanical and pb1'sical factors, other than impaired cardiac function,

may be contributo17 to the fo?'D8tion of thrombi. It seems apparent, however,

that all these factors are related again to an imderl71ng stagnation or relative stasis in the SJ'Btemic venous system._ Such a factor is apparent

in the constitutional types, which Rabinowitz and Holtzman (57) describe as

being prone to the developm1nt of venous thrombosis. 'fhey state that a at"lld7 of the individuals in whom venous thrombosis occurred revealed three veey important facts: Yirst, most occurred in the fifth and sixth decades. Second, these persons usually possessed a pyknic habitus, bad a pasty pallor to the facies, were inclined towards marked , and showed evidence of increased vagus tone-•respirato17 irregularity, , and dermograph­ ism. Others have noted that they were also thyroid resistant in their fail­ ure to react with to the use of thyroid extract. !bird, they were markedly eyposensitive to pain.

Miller and Rogers (48) consider obesity to be an important factor relating to thrombosis, and say that it is effective because the patient moves about leas in bed and has a more sluggish circulation. Rabinowitz and Holtzman also, in their discussion of factors •hich predispose to venous thrombosis, re-euphasize the significance of confinement to bed for over a week, and Shmidt (Vietor, 68) speaks of poor general condition and reduced resistance as deciding factors in embolic fatalities. In these instances the factor of relative venous stasis again appears to be of significance. PRO:BLB! OF PULMONARY EMBOLISM 21

Local venous stasis--retarded return circulation, phlebosclerosis, varicoa­ itiea--Rabinowitz and Holtzman consider to be ;yet another important factor predisposing to venous thrombosis.

Trauma. and operations for tra'UDl8. seem to have a high incidence of em­ bolism (Miller and Rogers, 48). Pigford (56) says that since tra1l1Da has

been considered a requisite to the clotting of blood, it has also been con­ sidered a necessa17 precursor of thrombosis. This conclusion ia not accept­

able to 1Ilall1'. Pigford add.a that, although in a large number of cases of thrombosis, trauma, with incidental injur;y to the endothelium of a number

of vessels, probabl7 plqs an important part, it is not present in all cases.

Pickering (54) finds that in ~ cases of thrombosis there is no recognizable change in the T&8cular endothelium.

J.n interesting and freq'\lent observation is that thrombosis and thrombo­ phlebitis is more prevalent after operations below the diaphragm tha.n follow­ ing operations on the brain and skull. This observation gives rise to some intere•ting speculation 'UpOn the etiolog;y of thrombosis, and is discussed b7

Bancroft and Stanley-Brown ( 5 ), who observe that: (1) In casea,in which the surgical approach has been through the abdominal wall, there is a con­ stant motion in the field of repair during the first fort7-eight hours; in operations on the skull, with a rigid skull cap, the field is at rest. '11th every breath taken and with the US'1lal postoperative nausea and Tomiting there is a constant thrust and pull upon the ope rat 1ve field, which might easily dislodge a thrombus or cause its extension into a larger vein. · (2)

The approach for an abdominal operation is through an area of subcutaneous fat, while in skull operations there is a relatively small amount of fat. PROBLEM OF PULMONARY EMBOLISM .22

With the insertion of sutures, often under too great tension, and with the application of a tight abdominal dressing, necrosis of the traumatized fat

~ result. Experimental work tends to show this factor to cause a marked

rise in the blood clotting index. (3) There tends to be a slowing of the

return flow of blood through the vena cava after abdo~inal operations, one factor in the causation probably being the usual postoperative distension and

consequent increase in intra-abdominal pressure. (4) A.fter an abdominal

operation there may be an increased influx of bacteria into the blood due

to altered absorptive capacity of the intestinal walls. (5) Dehydration,

with resultant increased viscosity of the blood, may occur after any opera­ tive proceedure. It is hard to estimate in the first forty-eight hours after operation, the increase of fluid output over the fliud intake. With post­ operative purgation, increased sweating due to postoperative elevation of the temperature, vomiting, and urination, the fiiud output is tremendously

increased. A.t the same t 1me the intake of fluids is usually markedly dim­

inished. The sa.ue exception may be taken to these conjectures of Bancroft and Stanley-:Brown that has been emphasized elsewhere in this discussion: that thrombosis is as frequent in medical as in surgical cases, and that as a consequence thrombosis, except when related to frank suppuration in an

cperative wound, IllSJ' have little direct relationship to surgical proceedures.

Biochemical factors concerned in thrombosis ~pulmonary embolism:

Steuer (66) has been quoted above as saying that stasis alone, or in assoc­ iation with endothelial injury, is insufficient, at least experimentally.to produce thrombosis. He adds that changes in the blood itself are doubtlessly necessary in order that thrombus formation take place. With this view PROBLEM OF PULMONARY EMBOLISM 23

Rosenthal (62) a&reea, saying, indeed, that all modern writers concur in the conception of the essential role of blood changes in thrombosis. As to the nature of the admittedly essential blood changes, there is, however, mu.ch disagreement.

It has long been recognized, according to :Bancroft, Xugelmass, and

Stanley-Brown ( 4), that a clot can be started by throwing out to the per­ iphery the blood platelets when the blood stream is slowed down. As these blood platelets clump along the portion of_ the vessel wall, there takes

place a coagulation of the blood, forming a red clot around this nucleus of platelets. Again, the great question which comes up is whether this forma­ tion of clot can take place with only a slowing of the circulation or with

tra:w:na., or whether there m:nst be first a change in the blood-clotting elements of the blood. That such blood-changes take place has been repeatedly dem­ onstrated, and Bancroft, Kugelma.ss, and Stanley-Brown, for example, found that, in eleven cases of proven thrombosis, phlebitis, or embolism which they studied, all had a high clotting index and a low antithrombin; in addition a small percentage of postoperative cases, not proven to have thrombosis, showed high clotting factors. !hey also determined experimentally that there is an increase in the clotting factors of animals following postoperative infection and gangrene, and a less increase following ether anesthesia.

A most interesting piece of work has been done by Mills (49, 50, 51) in connection with the effect of diet on clotting and basal metabolism. In this work he shows that a carbohydrate and fat diet will raise the basal metabolism, but will not increase clotting, while a protein diet not only raises the basal metabolism, but definitely increases the blood clotting elements. He attributes this phenomenon to some unknown factor connected PROBLEM OF PULMONARY EMBOLISM 24

possibly with the amino acids derived from protein metabolism, but seys that

11 a closer analysis of this protein effect 1n 1928 led us to the conclusion that it was intimately related to a more rapid platelet clumping and lysis which takes place". Bancroft, Xugelmass, and Stanley-Brown ( 4, 5 ) have gone further in demonstrating the relationship of diet and coagu.lability, showing that one can change the coagulation properties of the blood almost at will, a diet rich in nucleoproteina causing a marked increase in clotting factors, and a diet low in fat and protein causing a decrease in clotting factors.

The relation of the platelet count to thrombosis has been repeatedl7 studied. In postoperative, post partum, and post-febrile cases, it has been found by a number of investigators (24, 25, 42, 50, 58) that the platelet count, which s'Uffers a rather severe depression during fevers and parturi­ tion, begins to rise soon afterwards, reaching a peak on the eighth to the eleventh daT after the fever subsides, or after childbirth or operation. This peak usually shows a platelet count of almost twice normal. A sub­ sidence back to normal takes place in the next four or five days. Milla (50), who discusses this problem, points out that the platelet rise takes place

Just at the time most patients of the above classes are being allowed up for mild exercise and at the time when full diet is permitted. He asya: "Thus we have a period when all factors favoring thrombosis are at a maximum: the platelets are greatly increased; increased protein intake increases their tenancy to clump and disintegrate; and this is further aided by the exertion of moving around; and finalfy the action of the sluggish circ'Ulation is intensified during the first few days of sitting up or getting out of bed.• Pickering and Mathur (55) found, however, that tbe whole of the PROBLEM OF PULMONARY :BKBOLISM

platelets in the circulation can be disintegrated without provoking thrombosis,

and Pickering (55) and Mackay (44) showed that a. superabundance of platelets does not alone suffice for the inception of thrombosis. Hevertheless, Pickering (55) also agrees that •the presence of a great excess of circulat­ ing platelets probably contributes to the rapid growth of a thrombus, partic­ ularly when the histological structure of the thrombus shows laminae of platelets alternating with clotted blood, and this st1ggestion may account for the correspondence in time--of the clinical incidations of postoperative thrombosis with a rise in the JJWJlber of circulating platelets•. Again, Brock (14) says: •.A.lmst all observers, although not in full agreement as to the exact degree of importance of the platelets in coagu­ lation, seem agreed that the presence of an excess of platelets can certain­ ly result in a great acceleration of the rate of formation of the elot once the actual factors necessa17 for clotting have commenced the process. On the other hand, I bave seen thrombosis in cases where the platelet count showed no evidence of any thrombosis. Mackq bas also shown this. It ia clear that an increase in the number of circulating platelets cannot be the sole factor Causing the formation Of the thrombus; there is, however, strong evidence tbat the rise in J1WJ1bera is a factor of great importance in the actual final stages.•

Pickering (55) has studied the effect of tissue juices in thrombus formation. He states that after trauma tissue Juices 118.7 gain access to the blood stream, resulting in coagulation of blood. On the other hand, he says •many aspects of natural thrombosis rena.in obscure, SllCh as the CODIDOn absence of the rapid occurrence of intra.vascular clotting after ex­ tensive trauma when fresh tissue juices may enter the blood stream and the PROBLEM OF PULMONARY EMBOLISM 26 relatively high frequency of thrombosis during the puerperium, particularly after childbirth.• Pickering therefore concludes that the ingress of the juices of broken tissues into the circulation, although it DlaY' primarily ind'llCe hypercoag­ ul.ability of the blood and later provoke an increase of the platelets in the circulation, does not in itself suffice for the inception of thrombosis; but both these factors are probably important participants in the inception or growth of thrombi when the condition of the blood plasma favors the de­ posit ion and clumping of platelets or when the stability of the plasma colloids is reduced.

In recent years considerable attention has been given to the rate of settling of red cells as seen in various disease conditions. This phenomenon, as applied to the problem of thrombosis, has been recorded. Van Allen's observations, says Pickering (54), suggest that the speed of sedimentation of blood corpuscles is correlated with the changes in plasma which inaugurate clotting. Re found that sedimentation of cells preceded clotting, and con­ tinued until clotting occurred. Since the sedimentation rate is accelerated in many infections, and since the tendency to thrombosis is common in infec­ tions, it would appear that this phenomenon is associated with thrombosis. Pigford (56) sqs, however, that, according to Hegler, in the pol7c;ythem1as the sedimentation rate is slow and the incidence of thrombosis is high; and Miller and Rogers (48) declare that although J'ihraeua has noted that in­ creased sedimentation time of the red cells nay have some infl1l8nee in start­ ing the thrombus, there is as yet no definite evidence for this statement.

Many other blood cbangea have been studied, and a number have been said PRO::SLEM OF PULMONARY EM:BOLISM

to be important in the etiology of thrombosis. Dehydration, which causes

an increased viscosity of the blood, is mentioned by Miller and Rogers (48). Allen ( 1) believes definite and constant changes in the consistency of the blood--er7throcytes, leucocytea, prothrombin time, and fibrinogen--ocurring

after operation, to be co~tributor7 to thrombosis. Pickering (54) stresses

the significance of the various factors which qy- increase the agglutin­ ability of red cells, white cells, or blood platelets; thua platelet thrombi, for example, are seen in pneumonia and in anaph.Tlactic shock. Thrombi are frequent in both puerperal and inflammatory states, and both conditiona, according to Picltering,are distinguished by a uarlted excess of fibrinogen in the plasma and by increased sedimentation time •

.A. problem which frequently arises in consideration of the question of thrombosis and pulmonary embolism is that of the etiological relationship of intravenous medication. The aeries of University Hospital cases were examined, therefore, to determine whether intravenous therapy or other medication might bave been related to the occurrence of thrombosis and pulmonary embolism. Nothing of significance whatsoever in this relation­ ship could be discerned in the hospital records.

Speaking of the relationship of drugs to thrombosis, Pigford (56) says that some of the European authors believe tha.t present ~ methods of treat­ ment tend to increase the incidence of thrombosis. •They call attention,• he continues, •to the increased use of intravenous medications and anti• toxic sera. It is interesting to note that the fibrinogen content of the blood is increased following intravenous administration of gl-ueose.

Autopsies of patients dy'ing following the intraTenous use of drugs frequentl7 show wide-spread thrombotic processes. Hewlett calls attention to the PRO:SLEM OF PULMONARY EMBOLISM 28 product ion of minute thrombi in experimental animals following the injection

of certain tissue extracts and sera. The change in the mode of administra­

tion of digitalis from small to large doses is mentioned by the Continental authors. It has been suggested that the increased use of anesthetics, poaaibly through a change in colloidal activity of the cells, DIB1' influence postoperative thrombotic phenomena.•

Nevertheless, it is becoming generally accepted that intravenous in- ject ions are probably insignificant or at least uncommon causative factors in thrombosis. .A.ccording .to :Bartels ( 9), intravenous therapy has no apparent relationship to pulm:>nary embolism in the opinion of Xillian.

Giessendorfer, and .A.dolpb and Hopmann. Miller and Rogera (48) emphatically state that various predisposing factors have been discussed as causing throm­ bosis, such as preoperative intravenous medication, but there is no adeq'1l8.te reason for this assumption. 'Injections of arsenic preparations for syphilis,• they s87, 1 have not been followed by massive thrombosis and embolism.• The injection treatment of varicose veins was responsible for but five cases of embolism in 53,000 injections, or 0.01 per cent, they finally point out.

Thia incidence is considerably below the postoperative incidence of throm­ bosis and pulmonary embolism.

May'it be emphasized in conclusion of the consideration of the bio­ chemical factors in thrombosis and pulmnary embolism, which largely concern the blood, that :Bancroft ( 3) says: 1 Physiochemical studies reveal that blood plasma, ao long as its constituents are not dissociated by external forces, is a single complex in equilibrium, rather than a mixture of sub­ stances. The initial views of Harvey (1633) and of Woodbridge (1886) have come again into their own--'blood plasma is protoplasm, and clotting is the PRO:BL'lilM OF PULMONARY EMBOLISM last act of living blood'"· Therefore, II6Y not the factors, dbcussed as important in thrombosis, be considered, not as entitative pathological changes, but as inter-associated and inter-dependent relationships concerned in an intricate disease process--thrombosis. Miller and Rogers (48) agree that no one factor is of outstanding importance in thrombosis, and Bankoff

( 7) declares: •1 now wish to emphasize my opinion that thrombosis can never be regarded as due to only one class of causes: it is a pathological state which can arise from different causes at 8117 1ime the equilibriwn of the patient is destroyed•.

The £2l!. .Q! infection: Injury to the vessels and endothelium seems to be an important factor contributory to thrombosis, and has previousl7 been dis­ cussed. 'fith development of an inflammatory process in the wall of a vein, a tactor--phlebitis, considered by Joel (Bartles, 9 ) to be of dangerous significance--is set up. However, :Brown (15) studied eighty-seven cases of postoperative phlebitis without encountering one complicating pulmonar'J' em­ bolism. Thomas and .A.l7ea (67) reported thrombophlebitis as rarely 7ieldiDg fatal embolism, as the embolus is usually dislodged before phlebitis is re­ cognized clinicall.7. Bernb81m (13) reported a low incidence of grave pul­ monary embolism after phlebitis, but a high incidence of pulmonary infarc­ tion. Varicose veins be found to be of little, if any, significance, in producing pulmona.ey embolism. The role of infection in the frankly suppura­ tive types of thrombosis is unquestioned; it is considered, however, to be a separate problem beyond the scope of this paper, and will not be discussed in- detail. Hunt (37) suggests in discussion of postoperative pulmonary embolism that the most prominent factors related to pathological thrombosis are: PROBLEM OF PULMONARY EMBOLISM 30

(1) changes in tbs blood itself of such a nature as to increase its tendency to form clots; (2) blood stasis due to slowing of the blood stream from mechanical causes, depressed circulation, and lowered metabolism; (3) in­ fluence of disease processes, notably cardiovascular conditions; and, (4) infection. He says of the latter: •That none of the foregoing causes of throm­ bosis (l, 2, and 3) are sufficient of themselves implies the existence of some factor coD1JJOn to all. .An infection, of m>re or less specific character, alread1' resident in the host or introduced in some manner by the operation, b1pothetically would fill the need. Practically all writers entertain Dl\1Ch respect for the role of infection, but find objections to it as a cause of those cases of fatal embolism wherein no suppurations are macroscopically evident.•

In the University Hospital series of cases but seven revealed definite macroscopic evidence of a auppurative origin of the thrombotic processes. Thirty-five of ninety-three eases of postoperative pulmonary embolism re­ ported by H1l!lt showed primary or secondary wound infection associated with the thrombosis; the remainder were so-called "clean11 cases. Hunt points out, however, that wound infections usually considered clean have almost always received a considerable bacterial contamination, whether or not locally

manifest. He suggest that •occult" infections arising at operation DIB.1' account for certain complications remote from the wound, of which the various t)"pes of thrombotic processes are examples. He theorizes that

•a latent or occult infection activated by a variety of conditions which profoundly alter the metabolism, the circulatory mechanism, and the compo­ sition of the blood, beat answers the requirements of the situation.• Rosenow (60) takes perh8.ps a broader view of the situation, suggesting PROBLEM OF PULMONARY EMBOLISM 31

a microbic etiology of thrombosis and pulmonary embolism, but not attributing

the process specifically to invasion through operative wounds. :By means of special methods he isolated a diplostreptococcus, identical to one he bad

obtained a number of years before in similar cases, in each of five cases of postoperative pulmonary embolism and in one case of portal thrombosis, and also demonstrated a morphologically identical organism within the thrombus or embolus or infarcted areas in all but two of twenty-five additional cases.

The organism be found to be of low virulence, and to rarely cause lesions in

the various tissues, except those secondary to thrombosis or embolism. He says of his study of the behavior of the diplostreptococcus: "It often shortens the coagulation time of the blood of animals after repeated intra­ venous injection, and with pure cultures thrombosis sometimes associated with pulmonary embolism has been produced experimentall7 in three species of animals. Experiments have been successful with each of the four strains

injected and isolated from thrombi and with one strain isolated from foci of infection at the apexes of teeth. Such results have not been obtained in numerous experiments following injection of morphologically similar

organisms from cases other than pulmonary embolism. 11 Rosenow futhennore states that the factors, such as anesthesia, opera­ tive procedures, slowed circulation, and trauma of vessels, which are con­ sidered as etiologic in human cases, appeared to favor clot formation in experimental cases, but in some instances the mere injection of the organism sufficed. He contilllles: •The experimentally produced thrombi resembled those in man in their frequent formation in large veins and their large size; in being loosely attached, leading to embolism; in gross and microscopic appearance, including the deposition of fibrin; in not leading to suppura­

tion, in the presence of relatively small numbers of the diplococcus in pure PROBLEM OF PULMOUARY EMBOLISM 32 form within the thrombus, and in the relatively slight circumscribed areas of endophlebitis. The number of bacteria was relatively small and in some instances the production of a local focus, as in the eye, or even sub­ cutaneous injections, sufficed to incite the formation of thrombi.• He concludes that the diplostreptococcus, isolated from postoperative emboli and thrombi and used by him experimentally in different animals, is the coD1110n cause of postoperative and nonoperative massive thrombosis, leading to fatal pulmonary embolism, and perhaps of closely allied conditions such as infarction of the heart or brain. Indirect verification of the significance of Rosenow's work is evidenced in tbe failure to produce typical thrombosis by other experimental means. According to Rosenthal (62) stasis alone, from an experimental stand­ point, does not terminate in thrombus formation. He says that •this waa first shown by '.Ba'UIIlgarten in 1877, and has been verified by Miller and

Rogers, and by Armentrout. On adding endothelial injury to stasis, Bai:imgarten and more recently .Armentrout (1931) reported thrombus forna.- tion. It is questionable whether true thrombi were produced. More likely, mere coagulation took place, for Miller and Rogers, using sixty-three eats, were unable to produce true thrombi by double ligation of veins with scarring of the endothelium, interposition of muscle, etc.• It is seem­ ingl7 apparent, the refore, that these workers have set up a n'llmber of the predisposing factors conducive to thrombosis, but that some further essential factor is lacking; and Miller and Rogers did produce one tyPical thrombus in their aeries of experimental cases where infection had set in. THE INCIDDOE OF PULMONARY EMBOLISM•• CONSIDERA.TION OF CASI HISTORIES

General Considerations In comparing statistical compilations of various clinics in attempt to determine the incidence of thrombosis and pul.monar7 embolism, a wide variation is noted, which, says Rosenthal (61) may be explained by the fact that different types of clinical material are reported and that different pathologists evince var,.ing interest in these conditions. However, Rosen­ thal says, when an average is taken from all these reports, the similarit7 to the results he obtained in one thousand consecutive post-mortem examina­ tions is striking. The aver8ge for thrombosis taken from all reports (1930),

Rosenthal found to be 17.7 per cent, for embolism 12.5 per cent, and for fatal lung embolism 0.9 per cent. He obtained in his own work an incidence for thrombosis of 13.4 per cent, for embolism 7.6 per cent, and for fatal ·lung embolism 0.2 per cent. Belt (11, 12) has emplo;red extreme care in searching for pulmonar:r emboli at the time of post-mortem examination. He believes that probably there is no other autopsy finding more readily missed than pulmonary embolism, _and reports. that routine autopsies in the Department of Pathology­ at the University of Toronto and the Toronto General Hospital disclose pulmonar;r emboli in approximately ten per cent of adult cases in a series of 567 complete autopsies. Thirty-nine cases of pulmonar:r embolism were discovered at the Univer­ sity Hospital in a three year series of 309 post-mortem examinations--an incidence of 12.6 per cent. Included in this group of eases were seven PBO:BLIM OF PULMOD.RY EMBOLISM 34

cases of pulmonary embolism from sources of frank infection. This tYPe of

case Belt excludes from his series. With the exclusion of these cases from

the University Hospital series, for purposes of more accurate comparison,

the incidence of •bland" pulmonary embolism is found to be 10.4 per cent,

a figure almost identical to Belt's determination.

Relation of .Age to Pulmonary Embolism

Rosenthal (62) says the average age incidence for thrombosis and pul­

monary embolism, as found in the Toronto General Hospital, Canada, in the

Northwestern Univerait7 affiliated hospitals, Ciiicago, and in the Stanford

University Medical School, San Francisco, was about fifty J'8ars. .A.t the

Cook County Hospital, Chicago, the greatest number of cases occurred in

persons between forty-one and fifty years of age, while the highest per­ centa&e of thrombosis and pulmonary embolism was that of cases in persons

between sixty-one and seventy years of age.

European authors, according to Rosentbal, have reported an age incid­

ence for thrombosis and pulmonary embolism which is similar to that in this country. Without exception, the European authors have found the greatest number and percentage of cases of thrombosis and fatal pulmonary embolism

in persons between the ages of forty and seventy years. (Huhn, Klinke,

Singer and Morawitz, Oberndorfer, Hl5ring, Adolph and Hopman, Sellheim,

Geissendorfer, Killian, Grii0er, Hutter and Urban, Schulz, :Bauer, Q,ure).

Twenty-five of the thirty-nine University Hospital ca.sea of pulmonary

embolism were over forty-five years of age. The average age for the group was 45.7 years. PROBLEM OF PULMONARY EMBOLISM 35

Relation of Sex to Pulmonary Embolism According to Rosenthal (61) the ma.le represented by far the largest number of thromboses, as COJI!Pared to the female, in his series of one thousand post-mortem examinations. Non-fatal embolism showed the same re­ lationship. His two cases of fatal lung embolism were in fenales. In Belt's (12) fifty-six cases of pulmonary embolism there were thirty-five males and twenty-one females. On the other hand, but sixteen of the University Hospital cases of pulmonary embolism were males, and twenty-three were females. K'llhn (Rosen­ thal, 61) has shown a definite increase of thrombi in the fen:e.le over the ma.le. Fahr and Hu.eek (Rosenthal, 61) believe that sex does not play a note­ worthy role in thrombosis. For fatal pul:ironary embolism, Rosenthal says, all authors agree that the feml.e sex has the predominance. (m>-ring, Oberndorfer, Singer, Kuhn).

Relation of Race to Pulmonary Embolism Rosenthal (61) says that the incidence of thrombosis and embolism are about equal in the white and colored races. None of the University Hospital cases were colored.

The Sources of Pulmonary Emboli Often at necropsy evidence of pulmonary embolism will be found, and yet no thrombosis can be demnstrated. There are two reasons for this occurrence, which have already been pointed out: A thrombus JiaY' completely detach itself at its site of formation, leaving behind it no demonstrable alteration in the wall of the vein; or, more frequently, a sufficiently thorough search for the thrombus is impracticable. In thirty-tvro of the PRO:at.EM OJ' PULMONARY D.mOLISM 36

thirty-nine University Hospital cases the probable primary site of throm­ bosis was found or was suggested by clinical or autopsy findings. In all cases. excepting those of suppurative thrombosis, the emboli bad their apparent source in the veins of the legs or pelvis, or from the right heart.

Relation of Pulnx>nary Embolism to the Primary Disease The principle or primary diagnoses in the series of University Hospital cases are listed. (Table l) • .A. large proportion of the cases are cardiac, a number are infectious, and ~ are chronic debilitating processes. Su.ch a compilation yields little inforn:e.tion relative to the etiology of pulmonary embolism. It does, however, illustrate one significant, and not too generally recogni1ed fact--that pulmonary embolism may complicate practically any disease process persisting long enough to allow time for thrombosis to occur; it is freq'll8ntly encountered in medical. or non-op­ erated cases. PROBLEM OF PULMONARY EMl30LISM 37

TABLE 1. Classification of Oases of Pulmonary Embolism .According to the Primary Diagnosis

l. Cardiac--eleven cases.

a. Decompensation d'Ue to various causes--seven cases (9, 13, 14, 17, 20, 21, 25). b. Toxic goiter with myocardial failure--three cases (10, 11, 12). c. Subacute bacterial endocarditis--one case (23). 2. Conditions involving the abdominal viscera-ten cases. a. Oholecystitis--two postoperative cases (5, B). b. Kidney diseases--one postoperative case (16), and three un- operated cases (15, 24, 26). c. Umbilical hernia with partial strangulation--one case (3). d. Tuberculous enteritis--one case (6). e. .Acute pancreatitis with retroperitoneal hemorrbage--one post­ operative case (37). f. Amebic colitis with perforation--one case (38). 3. Suppurative processes with secondary infected thromboses-one post partum case (30), and six unoperated cases (27, 28, 29, 31, 32, 33). 4. Carcinoma--four cases.

a. Carcinoma of the uterus--two cases (22, 39). b. Carcinoma of the breast--one postoperative case (7). c. Carcinoma of the colon--one case (34). 5. Two postpartum cases (2, 4). 6. Miscellaneous conditions--five cases.

a. Benign hy-pertrop~ of the prostate--two postoperative cases (18, 19). b. Diff'use cortical atrophy--one case (35). c. Senile cataract--one postoperative case (36). d. Oystocele and rectocele--one postoperative case (1). f 'W"'"'lT

PROBLEM OF PULMONARY EMBOLISM 38

Fatal Pulmonary Embolism University Hospital records for a three-year period ending December 31, 1934 reveal a smaller percentage of pulmonary emboli found at post-mortem examination during 1934 than during either of the two preceding years, al­ though pulmonary embolism as the primary cause of death was mre frequent in 1934. In the three-year period 309 autopsies were performed. In thirty­ nine cases the post-mortem diagnosis of pulnonary embolism or infarction was made, and in nine cases pulmnary embolism was found to be the J?rimary cause of death. The percentage incidence was 12.6 per cent for total cases showing pulmonary embolism and infarction, and 2.9 per cent for cases of fat al pulmonary embolism.

Six of the fatal embolic cases occurred in a period of less than four oonths during tbe latter part of 1934. There had been no cases of fatal pulmonary embolism during the first eight months of 1934, but one case in 1933, and two in 1932. The situation was drama.tic, but no adequate ex­

planation of the outbreak could be determined. The present study was there­

fore undertaken, in an attempt to discover any unrecognized etiological factors in the cases.

It was found that the cases presented a diversity of diagnoses and

had been managed in a diversity of ways. Of the three cases seen in 1932

and 1933, case 1 was a postoperative gynecological patient, case 2 was an obstetrical patient eight days post partum, and case 3 was one of ventral hernia with partial obstruction which received only medical management. Of the cases seen in 1934, one (case 4) was a post partum obstetrical patient, two (cases 5 and 8) followed cholecystectomy, one (case 7) followed a radical mastectomy, and two (cases 6 and 9) were medically managed. The nine cases were rather readily fitted into two groups: three PROBLEM OF PULMONARY EMBOLISM 39

medically managed cases, all showing cardiac damag•; and six post partum and postoperative cases. only one of which showed evidence of cardiac damage.

In the entire group of thirty-nine cases showing evidence of pulmonary

~mboliam at autopsy, there were only twelve which were either postoperative

or post partum. or 30.8 per cent. Of this number, a rather high proportion, sb: of twelve, were in the fatal group.

On the other hand, a high proportion of the thirty-nine cases--53. 8 per cent-showed cardiac danege at necropsy, but only four of this group died of fatal pulmonary embolism.

In a series of 567 autopsies Belt (13) encountered fifty-six cases of :pulmonary embolism. Fifteen cases were of the type showing n:e.ssive emboli

which had been the cause of sudden death. The percentage incidence, curious­ ly, was almost exactly the same aa that for the University Hospital series-- 2.9 per cent as compared to 2.6 per cent. Furthermore, in Belt's cases of massive pulmonary embolism, the larger proportion, eleven of fifteen, were also surgical cases, and only four were medical cases; yet forty of his total group of fifty-six cases were medical.

The relationship of fatal pulmonary embolism to operative proceedurea can, therefore, not be neglected. Many attell!Pts are ma.de to dismiss these cases largely on the basis of circulatory stasis resulting from the opera­ tion and the enforced bed rest after operation. This explanation does not s'U:ffice, when it comes to the consideration of fatal embolic cases, for too great a proportion of the total cases are cardiac and yet non-fatal. In the

writer's opinion, more attention should be given to the work of Rosenow (60) and Hunt (37), which has already been considered in detail. These workers emphasize the importance of infection of a "bland" or •occult" type in the ------~-

PROBLEM OF PULMONARY EMBOLISM 40

causation of pulmonary embolism, especially that form which occurs after operation. (Hunt).

Another important fact is revealed in a review of l!elt's cases, as well as the University Hospital cases: Only occasionally is venous thrombosis recognized elinically prior to the embolic accident. But one of the nine University Hospital cases of fatal pulmonary embolism (case 8, page 56) com­ plained of symptoms of thrombophlebitis. l!elt says that probably sixt7 per cent of the emboli in his fifty-six cases arose from clotted leg veins, vessels relatively easy to examine and easy enough of detection when they

are painful, yet the majorit7 came to autopsy without recognition of the primary thrombosis during life. It has alread.1' been pointed out that the greater the local reaction accompanying a venous thrombosis the leas the likelihood of large emboli breaking off. If, in and around a vein, there is an inflammatory reaction of su.f'ficient intensity, says :Belt, to create local manifestations, the thrombus is likely to be securely attached to the vessel wall, and only small 1!8sses are capable of dislodgement.

The theory was postulated in the introductory section of this paper that, since pulmonary embolism depends upon the presence of a primary throm­

botic process, the amount of thromba.s which might break loose and reach the pulmonary arterial system through the blood stream would determine the gravity of the process; and thus the involvement of the lung is only an incidental or secondary occurrence. Since it has been repeatedly shown that no constant relationship exists between the incidence of embolism and the proportion of fatal cases, the occurrence of massive pulmonary embolism is well-nigh unpredictable. Consequentl7, it seems that a sudden rise in incidence of fatal cases is no cause for wonder, providing the total PROBLEM OF PULMONARY EMBOLISM 41

incidence of thrombosis and embolism has not increased, although it is cause for institution of more thorough prophylactic and therapeutic measures.

Postoperative and Post Partum Pulm:>nary Embolism Nine of the thirty-nine cases of pulmonary embolism seen at tbe Uni­ versity Hospital died shortly after operation (cases 1, 5, 7, 8, 16, 18, 19, 36, and 37). Three died shortly after delivery (cases 2, 4, and 30). In six of the cases death was attributed to massive pulmonary embolism. It

was of considerable interest to the writer that but four of this group, or 33.3 per cent, showed cardiac pathology, although twenty-one cases, or 53.8 per cent of the entire group of thirty-nine cases showed cardiac pathology.

Cardiac disease has been shown in the preceding sections to be one of the foremost predisposing factors in pulmonary embolism. Yet, if so small a group of cases as that at present under consideration, can be construed as characteristic, the implication would be that some factor besides cardiac disease is of m:>re importance in the postoperative cases of pulmonary em­

bolism tba.n in the medical cases. The infectious conception of pulmonar7 embolism and thrombosis propounded by Rosenow (60) and by Hunt (37 ).. and alrea.d¥ discussed, suggests a possible explanation.

Relation of Heart Disease to Pulmonary Embolism

Hegler in 1926 was the first to call attention to the marked rise in incidence of thrombosis in St. Georg Hospital, Hamburg, according to Rosen­ thal (62) who, in a rather complete survey of the literature~ found that there has been an increase in the incidence of thrombosis and pulmona.ry­ embolism in the clinics of Central Europe. .A.s a rule, he found, the actual ascent began in 1919, became universal in 1922 and reached its height in PROBLllll OF PULMONARY EMBOLISM 42

1928. Later than 1928 a decline became manifest. The rise was prevalent in the general, as well as the surgical, clinics, although more ne.rked in the latter. There was furthermore a rather closely parallel rise in the incid­ ence of cardiac and in the clinics of Central Europe, and a less marked increase in infections and suppurative diseases. Rosenthal believes that the hunger, nervous irritability, and lack of vitamins that were especially manifest during the period of inflation (1919 to 1924) in Central Europe account for the accentuation of cardiac and vascular diseases, and concludes that the rise of circulatory disturbances may be largely respons­ ible for the increase in thrombosis and e mbo~1am. No corresponding increase in thrombosis and embolism, or in vascular and cardiac disorders, was shown in reports from clinics in the United States and Canada. Such statistical reviews as that cited in the preceding paragraph suggest the importance of venous stasis and cardiac disease in predisposi­ tion, at least, to thrombosis and embolism, and Runt (37) adds: •As affect­ ing surgical thromboses the degenerative diseases play an important pa.rt. Indeed Kuhn attributes the increase of fatal embolism observed at the Path­ ological Institute at Freibu.rg to the prolongation of life by the present day treatment of chronic heart disease.• Twenty-five of ninety-three cases of postoperative thrombosis reported by Runt showed cardiac impairment. Rosenthal (61) studied the incidence of thrombosis and embolism in one thousand consecutive autopsies, and came to the conclusion that cardiac de­ con:g;>ensation and arterial changes apparently pl~ the more important role in the formation of thrombi and emboli. In one thousand consecutive autopsies there were 134 cases of thrombosis, seventy-ab: cases of embolism, and two cases of fatal.lung embolism. Jurtherm:>re, of 149 cases of decompensation of the heart in the entire series of one thousand cases, there were ninety- PROBLEM OF PULMONARY EMBOLISM four with thrombosis, or sixty-three per cent; of the 172 cases with arterial changes, seventy-six, or forty-four per cent had thrombi; and of the 511 in­ f ectious cases, but fifty-seven, or 17.4 per cent had thrombi.

Twenty-one of the thirty-nine University Hospital autopsy cases of pul­ m:>nary embolism showed evidence of cardiac pathology (cases 3, 4, 6, 9, and 10 to 26 inclusive). In four cases (cases 3, 4, 6, and 9) the emboli pro­ cess was so massive as to be the immediate cause of death. In the remainder (cases 10 to 26 inclusive) the embolieprocess sometimes complicated the clinical picture, but was often merely an incidental autopsy finding.

In a number of the University Hospital cases studied, notably cases

34 to 39 inclusive, there was present no apparent predisposing factor to suggest an explanation of the occurrence of thrombosis or pulmonary embolism, except perhaps the factor of circulatory stagnation or stasis due to rest in bed. All of these questionable cases showed pulmonary infarction; and all of the cases showing definite cardiac pathology also showed pulmonary in­ farction, excepting those cases in which embolism occurred too shortly prior to death for infarction to take place. Belt (12) interprets the occurrence of bland hemorrhagic pulmonary in­ farcts in his cases as evidence of impairment of the return circulation to the heart. This interpretation is based on the work of Karsner and Ash (39) who showed in 1912 that simple embolism does not produce pulmonary infarction.

Karsner and Ash :found that, in experimental animls, it was only by slowing the circulation considerably, as by ligation of the pulmonary vein or by compressing the lungs, that infarction puts in its appearance after pulmon­ ary embolism. They found that not only is stasis a necessary corollary of infarction, but also that, the greater the degree of stasis, the sooner true r111wr

PRO:BLEM OF PULMONARY EM130LISM 44

infarction will be likely to appear. In clinical cases such an impediment to the return circulation from the

lungs may be brought about, according to Belt (12), by compression or throm­

bosis of the pulmonary veins or by" or insufficiency of the mitral

valve. In his cases of pulDX>nary infarction ~elt found he was able to ex­ clude obstruction of the pulDX>na.ry veins, am. was therefore obliged to account for infarction on the grmmds of inadequacy of the mitral valve, when no more specific heart lesion was demonstrable. Indeed, in re-checking

the clinical records of these cases, he found that a mitral systolic murmur

had been heard in ue.ny.

The above interpretation of pulmonary infarction may be open to critic­ ism. However, it suggests an explanation for the occurrence of pulmonary embolism in otherwise unexplainable instances. It suggests the presence

of cardiac incompetanc7, which~ be a predisposing factor in the formation

of the primary thrombosis, as well as in the occurrence of infarction. Twenty-five of Belt's fifty-six cases were invalided with :myocardial in­ sufficiency, and twenty-four more presented evidence of a disordered heart with either infarcts of the lungs, or pathological changes in the heart, or both. Thus, he says, forty-seven cases, or eighty-four per cent, were re­ garded as having impairment of cardiac function. Be concludes: •From the present study it seems warrantable to emphasize another general principle _concerning the occurrence of thrombosis, a principle that has received onl7

casual attention in the literature, namely, that so-called spontaneous venous

thrombosis has a high incidence in cases of actual or impending congestive

heart failure. 11 ''

PROBLEM OF PULMONARY EMBOLISM 45

Pulmonary Embolism Complicating Septic Thrombosis A small proportion of infectious diseases, and, more frequently, suppura­ tive processes, notably mastoiditis, will give rise to septic thrombosis and pulmonary embolism. Thrombosis and pulmonary embolism complicating such con­

ditions are considerably less frequent than are thrombosis and pulmonary em­ bolism complicating cardiac disease. (Rosenthal, 61). Seven of' the Univers­

ity Hospital cases, or 17.9 per cent, showed infected pulmonary emboli sec­ ondary to primary septic thrombosis (cases 27 to 33 inclusive). This type of' case forms a.group more or less by itself, among thrombotic and embolic cases, in that the etiology is definite, while the etiology in the remainder of the cases is indeterminate.

Infection may play a role in all cases of pulmonary embolism, as it

has been previously pointed out, but this possibility is open to question. Relatively few of the postoperative and post partum cases in the series

were associated with cardiac disease; a possible explanation may be that

they were associated with •occult1 or non•suppurative low grade inflamma­ tory thromboses related to primary or seconda.17 wound infections. (Hunt, 37).

Relation of Therapy to Pulmonary Embolism The problem of therapy, and its relationship to pulmonary embolism has been previously considered (page 27). Rosenthal (61) states that patients seldom die of pulmonary embolism due to intravenous and injection therap7.

No relationship of therap7 to the occurrence of thrombosis and pulmonary embolism could be ascertained in the University Hospital cases. PROBL1Df 01 PULMOlWlY EMBOLISM 46

!he thirt7-nine autopsy cases of pulmonaey embolism seen in the Un1- vers1 t7 Hospital during 1932. 1933, and 1934 are presented in the following pages. In the preceding pages of this section on the incidence· of pulmoDa1'1 embolism attempt has been mde to bring out some of the impresaiou gained b7 a review of the cases. !he reYiew was not imdertak:en, however. with the purpose in mind of -.king a critical atud7 of theae case records, for th8 aeries of cases is too small. '!he atuq has been of interest becaue it demonstrates the total incidence of pulmona17 embolism at the Univerait7

Hospital to be comparable to that of other hospitals and clinics, and, mat important of all, because it demnstrates no increase in total pulmona17 embolism cases in 1934 corresponding to the increase in fatal pulmona17 embolism cases during that year.

It has previousl7 been pointed out that it DIB1' at times be a puzzling problem to determine whether an attached antemortem blood clot found in a pulmoDa.17 arteey is a pr1ma.r7 thrombus or an embolua which baa become attached aecondari]Jr. In the group of cases under couideration. a large

D'Ulllber wre found to show ante-mortem clots in the pulmonaJ7 arteries which were attached and which, consequently, in the case recor4s ware ter:aed thrombi. '?hat these so-called •thrombi• are moat probabl7 all em­ bolic in origin, it has previoual.7 been established. {Pages 15 to 17).

'fhe thirty-nine case records are di vicled for convenience into four groups which necesaaril7 overlap, for a number of the cases might be in­ cluded in m:>re than one group. Further discussion accompanies each case records PllOBLJM 01 PULMOH.ARY JMBOLISM 47

Gro1:1p l (cases l to 9 inelusiYe) consists of nine caaes of fatal pulJD)n&J'1' embolism.

Group 2 (cases 10 to 26 inclusive) consists of seventeen caaea showing the common finding of various forms of cardiac iupairment.

Group 3 (eases 27 to 33 inclusive) consists of seven cases of auppuratiYe thromboais with metastatic involvement of the l'tlDgs. Group 4 (cases 34 to 39 inclusive) consists of six miscellaneous caaea, all but one of which showed pulmon&J7 infarction, but no other definite evidence of cardiac impairment. PROBLEM o:r POLMOlWlY DlBOLISM 48

M. B. -- lbite. ma.rried. female, aged 50. Hospital number 40215. Bntered 8/22/32. hterior and posterior colporrhapl:JT; repair of hernia of cul-de-sac (ether anesthesia) on 8724/32. Died 9/2/32. Clinical cliagnoaia: C79tocele. llectocele. Hernia of cul-de-aac. Pulmonary embolism.

Poat-mortem diagnosis: J'atal palnionary em.boliam. J.aterior and posterior colporrbaplv', poat-operatiTe.

Clinical evidence of thrombosis and embeliamt •Patient bad a sudden abarp pain in tl:le epigastrium and com­ plained of her heart. She became na.rlmcll.7 d;rapneic,

Poat-mortem evidence of pulmonar;y emboli•mr Large long ante-mortem thrombi were found in the pulmonar;y . artery, meaauring 5 to 10 mm. in diameter and up to 10 cm.• in length. Similar, •terial was fomd in the right auricle and in the large branches of the right pulmoDa.17 artery. lvidence of circulatory f ailtare: Jione. Counent: Death occurred nine dqa poet-operative and waa clue to massive pulmnary embolism. !he apparent site of origin was the pelvic Teaaela, tbe thrombotic process extending from tbe operatiTe sites. PROm.JIM 07 PULMOnRY BMBOLISM 49

D. H. -- lhite. married. female. aged 33. Hospital number 40802. Bntered 10/3/32. Delivel"T 10/3/32. Posterior colporrha~ 10/10/32. Died 10 /11/32. Clinical diagnoaia: Pregnanc7, full-term. R. O. P. Deliver7 with mid-f'orcepa. PulmoDal'J' emboliam. Poat-mortem diagnoaiac fhrombi in internal iliac vein. Jatal palmoD&17 emboliem. Clinical evidence of thromboeis and embolism: Patient on the eighth post-partum da1" was taking tbe knee­ chest position when she felt a sudden pain below tbe sternum. She became faint, d1apneic, and c;ranotic. !he pulse was rapid. fluttering. Ox;rgen and atimalanta gave only temporarJ' relief. The patient died one hour and twent7-aeven minutes after onset of BJJDPtoma. Post-mortem evidence of thrombosis: .l large maas of a:nte-mrtem thrombus was found in the left internal iliac vein~ not attached to the wall. !here was no evidence of infection in the uteraa or evidence of thrombi in ita wall. Poat-mortem evidence ot pulmonar7 embolism: Several amall masses of ante-mortem thrombi were f012nd in the colllllOD pulmo:na17 arte17. Both l"IJDgll ahowed large llU&ea of gra;riah-red and compa.ratiTel7 firm thrombua, at the points of bifurcation of the main branches of the pulmon&r7 arteries, not adherent. lvidence of circulatol"T failure: Hone. Comment: In this case the probable source of the emboli was found-­ thrombosis of the left internal iliac vein. !hie is a tn>ical case of post-partum fatal pulmon&l"T e mboliam. PROBLIM 01 PULMONARY D4BOLISM 50

CASll 3.

M. L. -- lb.tte, married. female, a&ed 57. Roapital number 44668. Bntered 8/9/33. Died 8/11/33. Clinical diagnoaia: Ventral hernia. lnteettnal obtltructlon. Poat-mortem d.1agnoaia: Umbilical bernla with partial atrangalation. Cholelitbiae ia. Jatal pulmona~ emboliem. Clinical evidenc_e of thrombosis and emboliem: Varicoee ulcer on the left leg with aenral varicose veine. On 8/11/33 the patient audd.enl7 becaDl8 reatleaa and died within ten minutes. Poat-mortem evidence of thromboeia: Bone. '.l'he vein• of tbe legs, however, were not dissected.

Poat-mortem evidence of pulmon&17 emboliam: Several large ante-mrtem emboli wre foimd lJ'ing looaelJ' in the l'Qlll8n of the pulmon&rJ' arte~. fhe emboli were one to four inches in length and up to one centiater in diameter. There were also large thrombi ill the main branches of the palmoDarJ' artery. !here waa no infarct ion. lviunce of circulatory failure: Poat-mortem -- !ha heart mucle wa.a extremel7 eoft, and there was a great deal of fat over the nrface and mingled with the fibres. Comment: '.l'he T9l10U8 patholoa in the left leg nggeata a possible source of the emboli. Pathological findings alao suggest impairecl cardiac function. PROBLIM 01 PULMONARY lllM:BOLISM 51

G. S. - White, married, teale, aged 35. Hospital mimber 47824. Entered 8/6/34. Delive1'7 on 8/7/34 of three live ba'b7 girla, all breeches. Died 8/26/34. Clinical diagnosis: Triple pregnanc;y. Jull term. Pre-eclampsia. Post-mortem diagnoaiat !hrombo-phlebitia of ovarian vein. J'atal palmonary embolism. Infarction ot lUDg. Subinvolution of uterus. Atreaia of right Jallopian tube. Subacute nephritis.

Clinical evidence of thromboaia and embolism: On 8/10/34 and 8/11/34 the patient complained of ratber aharp paina over the precordium with only alight difficult7 in breatb­ iDB• On 8 /l7 /34 the patient had a severe pa.in in the right lower cheat with radiation to the ahoulder. Coarse ralea wre found in the lo11'8r right cheat with dimiahed breath aol1Dd.a. J'ollowiDg thia the pat tent caugbed cona~derabl.7, Yi th product ion of ao111 blood-atreaked aputim. On 8/fa/34 the patient had been aitting 12p in bed, auddenl7 screamed, collapsed, and died about aeven mirm.tes later.

Post-mort• evidence of thrombosia: !he uterus measured 14 cm. in length. On the posterior wall there was a ma.as of organizing blood clot, measuring 7 x 5 x 2j­ cm. There were thrombi in the amall i'eina of the uterine wall and about the posterior surface of the bladder. !he right ova~ ian vein was dilated to 1.5 to 2 cm. in diameter and filled with rather firm laminated thrombus. It extended throughout the length ot the vein• In the vena cava there waa a JDa.Ba of ante­ mortem thrombus, meaauring about 6 cm. in length, attached to the lateral wall. '!'he left ovarian vein contained a few ama.11 masses of thrombus near the ova1'7, but the remainder of the vein was free of thrombus, altho'Ogh the wall ns alightl.7 granular. Post-mortem evidence of pnl.JDDDa.17 emboliam: !he pulmona.1'7 artery was opened and probed; about fifteen grama of soft ante-mortem blood clot waa removed from the main brancbea of the pulmODa.rJ' arterJ'. . On opening the main .branch.ea of the pnl­ monar;r arteries ot the right l'UDg. large ma.ases of ante-mortem blood clots were encountered extendin8 down into the smlleat ramifications. ln the main p'Dlmonary ~rterial branch to the right lower lobe a rather firm. well organized thrombus waa en­ countered attached to the wall~ Thia thrombus was associated with a large infarct. !be left lUDg waa well-aerated throughout. llJTT'r

PRO:BLIM 01 PULMONARY DlBOLISM 52

Evidence of circulatory failure: Clinical -- Bone. of 160/90 was considered to be associated with a pre-eclamptic state. Poat-mortem -- The heart weighed 400 grams, and the left ventri­ cle measured 18 to 20 mm. in thickneaa. Valves and musculature were :normal. Comment: !he thrombotic process was apparently associated with a aub­ involution of the uterua, extendiDg from the small veina of the uterus to \he ovarian veins to the vena cava. .A.t autops7 a large infarct was found ln the right lmag with a large aaaoc1ated thrombwl, present for aeveral dqa and correspondiDg 1n probable duration to the attack of chest pain and dyspnea on 8/17734•. Death was due to fatal pulmonary embolism on 8/26/34. PROB.LIM OF PULMONARY EMBOLISM 53

CASJl 5.

JI. w. -- White, married, female, aged 39. lloapital number 48038. Entered 8/31/34. Cholec19tectoiv and appendectoiq under 250 mg. novac1ne spinal anesthesia, 9/10/34. Died 9/15/34. Clinical diagnoaiar Chronic cholecyatitia. Chronic appendicitta. On pathological examination of the tissues a diagnosis of choleeterosia of the gall bladder and negative appendix was made. Poat-mortem diagnosis: Oholeqstitia, post-operative • . .lppendectoDJ1', po.t-operat i ve. 'Jatal pul.mona.?7 · embolism. J'ibroida of uterus. Slight atelectaais of l'anga • .Ucaria infestation. Clinical evidence of thrombosis and embolism: !he patient progressed well until the fifth post-operative daT when she a'Uddenl7 eat '\l,P in bed, breathing rapidlT and showi1:1g considerable c;ranosia. She complained of no pain. She was given mrphine, caffeine sodio-benzoate, and digal.en intra­ venomlJ'. but she died two hours and twent7-five minutes after the onaet of the •JBPtoma. Diagnosed as probable pulmonar7 embolism.

Poat-mortem evidence of thromboaias The operative sites were clean and heallng normalq. Bo thrombi were found in aD7 of the large veins 1 although the veina of the legs were not explored.

Post-mortem evidence of pul.monar,y embolism: There was an ante-mortem thrombus in the pul.m.naey artery 60 cme in length. !be thrombas was firm and granular, and of practicall.7 uniform diameter, about l cm. There wre no thrombi in the branches of the pulmon&r7 arteries and there were no in.tarots in tlle lunge.

~vidence of circulatory failure: BODe. Comment: On post-mortem examination no change was noted in the vessels of the pelvis. :Because of the enormous length of tbe embolus--a1xty centiDletera--one can conclude that the onl7 possible source could be a large vein in one of the legs with the thrombus perhaps ex­ tending into the pelvia. There was no hietor,y of varioaitiea ot the legs or of thrombo-phlebitia. PROBI..EM O:r PULMONARY IMBOLISM 54

CASE 6. V. x. - lh1te, female, aged 14. Hospital number 48352. Kntered 10/7/34. Died 10/13/34. 011n1cal diagnosis: Subacute nephritis. ·Parasin"ll8itis. acute, right. Lateral pha17J1gitis. Post-mortem diagnoa1a: Tuberculous enteritis. lheimatic heart disease. Mitral 1nsutficien07. J'atal pulmona17 emboliem.

Clinical evidence of thrombosia and emboliam: On the morning of 10/13/34 the patient became c7anotic and the respirations labored and gaaping. The pulse was weak and threa~. but the tones at the apex were relat1vel7 strong. !he patient elepelled frotb7 naterial from her nose and expired about twelve mimites after the onaet of S1'11I.Ptoma. Post-mortem evidence of thrombosis: Bone.

Poat-mortem evidence of pul.monar7 embolism: On probing the common pulmonar;r arte17 several masses of ante­ mortem thrombi were tcnmd; the largeat of these measured 7 x 1 cm. Evidence of circulato17 failure: llisto17 of in 1931. On entrance the patient com­ plai?18d of ~apnea on e:xert ion. On exa:minat ion, there was a soft s7stolic murmur at the apex, and the rbTthm waa regular but fast. Poat-mortem - !he heart weighed ax> grams. The mitral orifice admitted three fingera; the edgea of the m1tral cuapa were ao­ what thickened and rolled; and there ._. voma thickening of the chorda tendinae. 'lbs aortic cuapa were slightq thickened an4 there were a few adhesions in tbe anterior commisnre. The other valves, mwaculature, and coronar)" arteries ahowed no change. Comment: !hie was an unusual case in that fatal pulmonary embolism is rarel7 seen in a patient as young as this one. It 11187 therefore be concluded that the heart pathology was an important tactor for mere bed rest is rarely complicated b3' pulmna17 embolism in children and adoleacente. PROBLIM 01 PULMONARY IMBOLISM 55

K. P. - White, married, feuale, aged 63. Roapital number 48368. llntered 10/9/34. Radical maatectolltl' lUlder gas-ether anesthesia on 10/2JJ/34. Died 10/22/34. Clinical diagnosis: Carcinoma of the left breast of a duration of about one 7ea,r. Varicosities of both legs. Varicoae ulcera of both legs. Marked rectocele. Poat-mortem diagnosis: J'atal pulmona17 embolism. Carcinoma of breast, post-operative. Carcinoma. of :fundus of uterus. P7elonephroa1s of right k1dne7. Compenaatary hy'pertrophT of left kidne7. Healed duodenal ulcers. Diverticuli of colon. Polypi of colon. ~ilirubin calculi in gall bladder. C7stitis c7atica.

Clinical evidence of tbromboaia and emboliam: Histo17 of •mlk leg• fifteen 7ears ago, and of ulcera on the right leg more or l••• contimiall7 for the paat fifteen 7eara. On e%8Dlination var1cositiea were :noticed on both thigba, and there were ulcers on both lower lega. J>%7 beat with local application of olive oil was employed in management of the ulcers during the patient's hospitalization. The patient died auddenl7 two cla1's after a left radical maatectoJl\V', apparentl7 a respirato17 death. She lived 0Dl7 fifteen minutes after the onset of a7D1Ptorm. Poat-mortem evidence of thromboaiat Hone.

Poat-mortem evidence of pulmo1la?7 embolism: !he pulmonar7 arter.r was filled with a large mass of ante-mortem throJD'bws. !here were similar masses 1n the main and smaller branches of the pulmona17 arte?7. !here were no areas of in­ farct ion.

J:vidence of circulator,y failure: I'one. Oommentt The patient, who showed no clinical or pathological evidence of Cal"diac disease, died suddenl.7 two dqa post-operative with a maes1:ve pulmonaey emboliam. The primar1' site o:r the thrombotic process was not determined at necropa7. However, the presence of variceae veins and ulcers , and bistorT o:r phlegmaaia alba dolens auggeat the source to have been some of the large veina in the lega. Venaaa •tasia due to enforced bed-reet over a period of nearl7 two weeks was probabl.7 an important etiological factor. PROBLEM O"I PULKONARY EMBOLISM 56

CASI a.

S. X. - lb.ite, married, female, aged 47. Hospital number 48490. Entered 10/25/34. Chole07Btecto1117 and comnon duct drainage on 10 /31 /34. Dled 11 /9 /34. Clinical diagnosis: Chronic cholec7atitia. Acute cbolec7atitia on examination of pathological specimen. Oholeli thiaaia. Poat-mortem diagnoaia: Oholec78tit1a, post-operative. J'atal pulmonary embolism. Mild atelectaaia of right lung.

Clinical evidence of thrombosis and emboliamt 'rhe patient had made an apparentl7 uneventful post-operative recover)" until the ninth day attar operation when during the night she complained of cold feet and pain in the legs 'below the knees. In the morning she had a sudden pain in her cheat and became markedly ~neic. The e%preaaion was one of ex­ trea anrlet7. She died twent7-five minutes after the onset of &711lPtoma.

Post""lllOrtem evidence of thrombosiat !he superficial veins on both legs were visible; those on the right were distended. The veins of the legs were not opened. There wre no thrombi in the iliac veins. !here was no roi:Jgbening of the intina of the Tena caTa. !he operative site was clean. There waa a atone high in the cmmon duct, but it did not appear to be causing obatruction.

Poat-DiOrtem evidence of pal.nr>Da17 emboliem: There were two large masses of ante-mrtem tbrom'bu in the main branches of the pulmona17 arteey. The larger branches of tbe arteries to each lung contained aniall maasea ot ante­ mortem thrombu.a. Th.ere were no areas of infarct ion. Evidence of circulato17 failure: lone. Comment: This case of fatal pulmonar7 embolism presented an unuaual s711lPtom-complex-pa1n in the legs and cold feet ahortlJ' before the occurrence of the pulmoJl&J'1' 41Dbollam--suggeative of acute thrombo-phlab1t1a. It mQ" be concluded that the source of the palmonar1 emboli were the ftins of the legs. PROllLEM 01 PULMONARY IM:BOLISM 57

C. S. -- White, ma.le, aged 72. Hospital muaber 4889'1. Bntered 12/ZJ./34. Died 12/12/34. Clinical diagnoaia: Arteriosclerosis. Ptalmona.1"7 embolism. Post-mortem diagnosis: 1atal pulmona.17 embolism. OoroDa.17 aclerosia. Myocardial fibrosis. Pelvic thrombosis. A.rterioaclerosis, generalized.

Clinical evidence of thrombosis and embolism: On 12/12/34 the patient, who was sent to the hospital as a case of probable chronic gall bladder irritation, was apparentl7 feel­ ing well when he walked into the admitting room. .A.tter taking a bath be was seized with a sudden attack of qapnea and c7anosia, accoupanied 'b1' a •cold sweat• • He complained of diatreas over the precordium. However, the was regular and slow. In the ward the patient waa observed to be extremel.7 qspneic. The skin was pale, and a grayish CY"anosia was noted. !he patient was frightened and convinced he was about to die. He did not respond well, but said he had had a similar attack about one month ago. Morphine did not greatl.7 relieve the restlesaneaa. The patient died about twenty-five minutes after the onset of the s7111Ptoms. Post-mortem evidence of thrombosia: There were a few small thrombi in the plexus around the prostate and bladder.

Post-mortem evidence of pulmonary emboliBJlll TheTe waa a ma.as of ante-mortem thrombus about 23 cm. long lodged in the pulmonal"T artery. In the various branches of the pulmonaJ7 arteries were a n'OIDber of various sized thrombi, some of which were firml7 attached to the arterial walls. !here were several infarcts in the li:mgs. Evidence of circulatol"T failure: Clinical _.,. !he referring physician stated the patient had had heart trouble and arteriosclerosia for some time. The patient died before hia histoey could be taken or adequate stuey of the cardio-vaaeular and other systems could be made. Post-mortem -- The heart weighed 480 grams. The corona.1"1' arteriea showed. extensive sclerosis. !he lumen was definitel.7 diminished in the left corona17 arte17, but a COJll>lete oecl'08ion was not demonstrated. Small areas of aottening and scarring were seen in the ventricles. PRO'BL114 OJ PULMOIU.RY JMBOLISM 58

Commentt Thia case of fatal pulmonary em'bol18m was of especial interest because there was a history of previous leas severe attacks of s71D.Ptoma suggesting the occurrence of pulmonary embolism, and because the autopsy findings of emboli of various agea in the lungs.confirmed the clinical interpretation. !he caae was of further interest because atagnation of circulation due to con­ finement to bed was not a factor, while cardiac pathological changes were marked. PROBLIM or PtJLMONA.RY llMBOLISM 59

ClO 10.

ll. JL - White. married, male. aged 60. Hospital number 37526. Entered 1/8/32. Died 1/12/32. Clinical diagnosis: !oxic goiter with nvocardial failure and auricular fibrillation.

Post-110rtem diagnosis: Colloid ad.enema of tb1'roid. Cardiac hy'pertrophy and dilatation. Infarction of l"UDgs. kidne7s. and right popliteal artel'J'. Mural thrombi of auricles.

Clinical evidence of thrombosis and embolismt Swollen. painful right leg on which the akin blistered. and peeled awa;r.

Post-mortem evidence of thrombosis: Mural tbrombi in auricles. !hrombus at bifurcation of poplitaal arter7. Infarcts in kidneys.

Post-mortem evidence of pulmonal'J' embolism: Several small thrombi were found in tbe pulmona17 arterial branches. with infarction.

Evidence of circulator7 failure: Clinical -- Cardiac failure and auricular fibrillation. Poat--mortem -- Cardiac }Q"pertropb7 and dilatation.

Oommant: There was evidence of thromboaia in both arterial s79teme, and there were mural thrombi in both auricles. The mral thrombi m&1' be considered priml'J', their forma.tion being aesociated w1 th the cardiac h1pertrop~ and dilatation; and the other vaecular occluaiona .,..,. be considered as metastatic, or embolic, probabl.7 from the auriclee. Pulmonal'J' embolism is considered an unusual occurrence in tqroid disease. This case and the two following cases of tbJroid dieeaae, however, showed post-mortem evidence of palmonary embolism. !he aesociated cardiac pathology present in each case probabl.7 beat explains the occurrence of pulmona17 embolism in the three caaea. PROBLD OF POLMONARY IMBOLISM 60

CA.SI 11.

D. P. - ei.1te, married, female, aged 39. Hospital n'lllllber 38090. lDntered 3/17/32. Dled '6/'Z4132~ Clinical diagnoaia: SJ'.Philla. Cardiac failure. '?one goiter. Post-mortem diagnosle: Confluent broncho-pn8UJ1Dnia, left. Pulmona17 infarcts, right. A.cute auppuratiTe nephritis. !hromboaia of h1'pogastric vein, right. M7ocardial degeneration. B)perplaaia of tbT?'oid. Clinical evidence of thrombosis and embolism: lTona. Post-mortem evidence of thromboaiat !here were no thrombi in the heart. Thrombosis of the right bTpogaatric vein.

Post-mortem evidence of pulmonary embolism: .A 4 x 6 cm. infarct was foll!ld in the lower lobe of the right lung.

~vidence of circulatory f ailuret Clinical - Dyapnea. Swelling of feet and ankles. Poat-mortem -- 117<>cardial degeneration. Comment: The presence of a thrombus in the right bypogastric vein suggests the pelvic Tesaela as a source of tlle pulmonary embolus which caued tbe infarction. PRO:m:Jll4 OF PULMONARY EM!OLISM 61

CASB 12.

J. K. -- White. married, female, aged 52. Hospital number 38277. Entered 3/17/32. Died 3/24/32.

Clinical diagnosis: H7pert~idism. Cardiac failure. Poat-mortem diagnosis: .ldenomata and }qperplasia of thlroid. 111'ocardial degeneration. Edema of lUDgs. Chronic passive 9011gestion of liver and spleen. !hromboe1a of pelvic veins. Pulm>na.?7 infarction.

Clinical evidence of thrombosis and embolism: Jrone.

Poat-mortem evidence of thrombosis: !here were no thrombi in tbe heart. !here were small thrombi in a number of the vessels of the pelvic walls.

Poat-mortem evidence of pul.DX>nary embolism: Infarcts in both lungs. Thrombi caueing the larger infarct were found.

Evidence of circulatory failvet Clinical -- Dyapnea. Swelling of lower extremities. Post-mrtem - Chronic uvocardial dsgenerat ion. Edema of lunge. Chronic passive congestion of the liver and spleen.

Comment: Dr. J. P. Tollman: "There are small thrombi in a n'Olllber of the vessels of the pelvic wall, and we interpret tbe pulmona17 in­ f arcts as coming from this aoo.rce 11 • PROlltllM 07 PULMONARY llmOLISM 62

C.lSI 13.

!. 'I. -- White. single, male, aged 66. Hospital number 38664. Entered 4/15/32. Died 5/10/32.

Clinical diagnosis: Coronary occlil8ion. X-rq - Moderate cardiac enlargement stJ&gestive of general loss of cardiac tone and 1D7ocardial inau:fficieDCJ".

Post-mortem diagnoaiaJ Cardiac infarction with mural thrombi in the left ventricle. Thrombosis of internal iliac veins. Pulmona17 infarct ion. Right hydrothorax. Generalized arteriosclerosis ••

Clinical evidence of thrombosis and embolialllf Bone.

Poat-mortem evidence of thrombosia: Small ante-mortem thrombi in the tip of the right auricle. Large thrombus in the left ventricle. Several thrombi in the internal iliac veins. Smaller veaaela of the pelvis were uniformly filled with thrombi. Corona1'1' thromboaie.

Poat-mortem evidence of pulmonary embolism: Right limg -- The pulmonaey artery to the lower lobe waa filled with large non-attached emboli. Another throm'bwl was found in the center of the lobe, with infarction. Large. recent thrombi were found near the hilum. Left lung - Infarcts 1lp to 7 cm. in diameter were found.

Evidence of circulatory failure: Clinical -- Precordial pain. Shortness of breath. Moderate cardiac enlargement. Poat-mortem -- Chronic passiTe congestion of the liver and spleen. Cardiac infarction. Left coronary arte17 thromboaia. MarkBd coronary acleroaia. Comment: _ Thia cue ta another showing circulatory failure due to cardiac patholog. There are two possible so1ll"cea of the pulmona17 emboli: mural thrombi in the right avicle, and thrombosis in the internal iliac veins. PROBLIM OF PULMONARY IDOLISM 63

CASI 14. 1. D. -- White. married, female, aged 51. Hospital nllDl.ber 38798. Enter~d 4/26/32. Died 5/10/32. Clinical diagnoaia: Decompenaated heart. lifTocardial degeneration. X-nq -- Marked cardiac enlargement suggestive of Jl\YOCardial inaufficienc7. Post-mortem diagnosis: Cardiac infarction with mural thrombi in the left ventricle. Thrombosis of iliac veiu. Pul.D.10nary infarction. Infarct in spleen. Dependant edema, generalized.

Clinical evidence of thrombosis and embolism: .A.n entry in the patient's record on 5/3/32 stated that there had been hemopt7ais for three clqs. '!he patient complained ol pain over the liver. On percussion there was dullness over the lower lobe of the right lung. Poat-mortem evidence of thrombosis: Thrombi wre adherent to the anterior wall of the left ventricle and interventricular aeptum, aaaociatad with cardiac infarctions and marked coronary sclerosis and tortuoait7. There was extensive thrombosis of the internal iliac vein on both aides and in the lateral veins about the uterus. (Uterus was negative).

Post-mortem evidence of pulmonary emboliem: Right lUDg -- .A. large heD.10rrhagic infarct was found in the lower lobe. .A. large mass of ante-mortem thromba.a, adherent to the walls, was found occludi:ng the vessels to the region. Several more recent infarcts were present. Left lung -- Several l to 4 cm. infarcts with small thrombi were present.

Evidence of circulatory tail'ure; Clinical -- Attacks of precordial pain. Dependent edema. .A.nasarca. Poat-mortem -- Coronary sclerosis with left ventricular infarction. CoD11Dent: CirC1llator7 failure and consequent venous stasis suggests an ex­ planation for the occurrence of thrombosis of the internal iliac veins. lmboli from thie source lodged in the lUDga with resultant pulmonary infarction. PROBLEM OF POLMOD.RY DBOLISM 64

CASI 15. J. P. - White, married, me.le, a&ed 70. Hospital number 39319. Euter~d 6/10/32. Died 6/18/32. Clinical diagnosis: Old prostatectoiq (1930). Not otherwise diagnosed. Symptoms a"Uggeated a terminal uremic state, but ll. P. N. was 36.5 mg. ~. :Blood sugar on admission was 268 mg. "1· Post-mortem dlagnoaia: Pyelonephri t la, marked. Arteriosclerosis, generalized. Cardiac lv'.Pertropb1' and dilatation. Chronic m;yocardltia. Pulmonary embolism. Clinical evidence of thrombosis and embolism: Bone. Post-mortem evidence of thrombosis: 11lone.

Post-mortem evidence of pulmonary embolism: .A. rather large ante-mortem thrombus was fo'Ul'ld in the pulmonary branch to the left lung. The thrombus was not attached, and th.ere was no corresponding area of infarction. lvid.ence of circulatory failure: Poat-mortem -- Cardiac h1Pertroplq and dilatation. Chronic Jll1'0e&rditis. Comment: !his was a case of pulmonary embolism associated with cardiac failure, without presence of poet-mortem evidence of thrombosis elsewbare. PROBLIM O'I PULMOHARY EMBOLISM 65

CASK 16.

M. B. -- White• married, female. aged 63. Hospital number 40294. Entered 8/tn/32. BephrectollG". local anesthesia, 10/16/32. Died 10/18/32.· Clinical diagnosis: 14Tocard1tis with beginning .cardiac decompensation. l17dronephrosis. Post-mortem diagnosis: BephrectollG". post-operative. Thrombosis of pulmonat'7 arteries. Carcinoma of right breast, recurrent, metastatic.to 1~ node. Atelectasis of lungs. l't0Dgiald*»J.?c11ta-ot;the liver. Clinical evidence of thrombosis and embolism: Bone. Post-mortem evidence of thrombosis: Bone.

Post-mortem evidence of palmonary embolism: Considerable amo'1llts of recent and friable ante-mortem thrombi were found firmly attached to the walls of the pul.mona!7 arterial branches in j;he lungs. Grqiah-red vegetati• masses, appearing to be infected, were present in the piWoonar7 arteries. There was narked atelectasia of both lower lobes. lvidence of circulato1'7 failure: Clinical -- Ea.rl;r IJG'Oe&rdial failure. Post-mortem -- Scarring of myocardium. Comment: Death occurred two da7s post-operative. A probable source of the emboli was the infected area. A contr1but&r7 factor was a failing circulation. PROBLBM OF PULMONARY IDOLISM 66

OJ.SI 17.

JI. O. -- White, married, male, aged 64. Hospital number 41745. Entered 12/19/32. Died 12/29/32. Clinical diagnosis: Cardiac decompenaation on a vascular basis. Post-JDOrtem diagnosis: Cardiac hl'pertro~. Recent cardiac_ infarction in the left ventricle. Broncho-pneumonia. Cerebral infarction. Infarcts of kidne79 and spleen. _lllmbolism, left pulm:>na17 arte17. Clinical evidence of thrombosis and embolism: J'one. Post-mortem evidence of thrombosis: Thrombi in both auricles and left ventricle. Poat-mortem evidence of pulmollaey embolism: Recent embolus in left pulmonar7 arteey. Evidence of circulator7 fail"D?'e: Clinical - Evidence of cardiac decompensation. Post-mortem -- Cardiac hypertro~. Recent infarction in the left ventricle associated with coronary sclerosis and thrombosis. Thrombi in both auricles and the left ventricle. Comment: There were m11ral thrombi in both auricles and the left ventricle; these were probabl1' the source of polmona17 emboli and of the emboli causing infarcts of the kidneys and spleen. PROBLD 01 PULMOla.RY EMB)LISM 67

CUI 18.

S. S. - &ite, aingle, male, aged 75. Roe_pital number 41915. htered 1/2/33. Perineal proatatectonv, 1{19/33 (sacral anesthesia with gas). Drainage of blood-filled c79tic cavit7 beneath posterior sheath of recti muscles, 2/6/33. Died 2/21/33. Clinical diagnosis: Proatatic hJpertrop}V', benign. Jf.P.lf. on admission was 38.7 mg. f,. Ramatocele, postoperative. Poat-mortem diagnosis: Prostatecto1111". postoperative. Hemorrhage into anterior abdominal wall. Thrombosis of left femoral vein and veins of the left arm. PulmoDar7 infarction. Infarction ot heart macle, old and recent. Clinical evidence of thrombosis and embolism: On 2/12/33 it was noticed that the patient's left leg was swollen to twice normal size. On 2/15/33 the left arm and leg became swollen and painful. Post-mortem evidence of thrombosis: !he left femoral vein was o~cluded by a rather firm blood clot which was beginniDg to soften in onl.7 a few places. Several veins of ti. left arm were found to be occluded by rather firm thrombi, and some purulent uaterial was found in these veaaela. Poat-mortem evidence of pulmonarJ" embolism: Right lung - The lower lobe presented a partiall.7 broken down infarct along the lowr border of the lower lobe, the apparent cause of the pleurisy with eftuaion faand on thia aide.

Zvidence of circulato17 failure: Poat-mortem -- Large areas of scarring were found in the left ventricle, the largest measuring 3 X 4 cm., and aeveral more recent infarcts. Marked sclerosis of the coronary arteriea.

Comment: The probable source of the embolu cauing the p1JlmonaJ7 infarc­ tion was the venoua thrombosis of the left femoral vein or the veins of the left arm. Ztiological factors were impaired cardiac action and prolonged enforced bed rest. The caaa Be7 be considered one ot postoperative pulmoD&rJ' emboliam. ------

PROBLEM OJ' PULMONARY llMBOLISll 68

CASI 19. J. G. -- White. married. male, aged 51. Hospital m:imber 42294. :!Bntered l/'8J/33. Transurethral resection, 2713/33. Died 2/22/33. Clinical d1agnoaia: Carcinoma of prostate. N.P.lT. on admission was 31.5 mg. fo. Metaataaia to longs. Left sided hemiplegia, old. Coronary thrombosis. x-ra:r -- .A.ortic valvolar lesion with left ventricular and right auricular lq'pertro~. Passive congestion of the lung field. Gaetro-enterostoiq 1n 1924 for peptic ulcer. Post-mortem diagnoalat :Benign bnJertropq of prostate. Becrosia of bladder epitheli'Ulll. Pyelonephritla. Thrombosis of pelvic veins. Pa.l.mt.>nar'1' infarct ion. Cardiac infarction, old and recent. J'alae porencephaly, right cerebral hemisphere. Healed duodenal ulcer. A.nterior gaatro-enteroato~. Clinical nidence of thrombosis and embolism: .A.ttaclta of chest pain on 2/16/33 and 2/17/33 were interpreted as coroDa.%7 thrombosis and not pulmonary embolism. Poat-mortem evidence of thrombosis: The femoral veins were occluded by a thrombus which extended into the interior vena cava. to the level Qf the lower border of the kidney. !he thrombus was softening and contained pariform material in aome places.

Post-mortem evidence of pulm:>nary embolism: Left lung -- On opening the ma.in veaaela in the left lUDg a large thrombus was found lodged at the first bifurcation. It was firml.7 attached and did not co~letely occlude the lumen. Right lung .._ .A. 4 X 5 cm. infarct waa found near the base of the lower lobe. !here were several other scattered areas of infarc­ tion, some quite recent. There were several large firmly attached thrombi in the vessels. lvidenee of circulatory failure: Clinical -- Severe chill on 2/16/33 followed 'by knife... like pains in region of heart. with irregular palee. marked ~pnea, and fibrillation at times. Interpreted as coronary thrombosis. There waa a similar attack on 2/17 /33. · - Poat-mortem -- Moderate enlargement of heart. The left ventricle showed an area of scarring extending from the apex of the left ventricle to within 1 cm. of the atrioventricular ring. Several small quite recent areas of infarction. Marked acleroaia and calcification of coronary veaaele. PRO:BLD OF PULMOIARY ll.mOLISM 69

Comment: .A. probable source of the emboli was found in the tbi"ombus in the inferior vena cava. Cardiac failure and postoperative enforced bed reat were doubtlessly important causative factors. PROBLEM 01 PULMONARY BMBOLISM 70

CASlC ao. p. p. -- 1h1te. married. female, aged 47. Hospital number 42725. mntered 3/5/33. Died 3/19/33. Clinical diagnosis: Congestive heart failure • .A.ur-icul.ar fibrillation. Poat-mortem diagnosis: Mitral atenoaia and inaufficienc7. Chronic passive congestion of lungs. liver. 1ddne79, and spleen. Pu].m:)nary intarction. Clinical evidence of thrombosis and embolism: ll'one.

Post-mortem evidence of thrombosis: .A. large ante-mortem thrombus was found in the left auricle.

Poat-mortem evidence of pulmonary embolism: In both lungs thrombi were found deep in the pulmonary arteries. There were infarcts in both upper lobes. Evidence of circulatol'T failure: Clinical -- Complaints of shortness of breath. cough. weakness, and swelling of the feet. !he patien~ had some ahortnesa of breath since the age of 13. On examination a total irregul.ar1t7 of the heart was noted. !here was a s79tol1c murmur beat heard at the apex and a soft diastolic murmur be~t heard at Erb'a point. Poat-mortem -- !he m1 tra.t orifice measured about l cm. in diameter with f12sion of the cuepa. !he right ventricle mea81l1"ed 8 to 9 m. in thickness. !he heart weighed 360 grams. Comment: .A. possible source of the pulmnary emboli was not found. '!his is another case of pulmona.!7 embolism associated with heart f allure. PRO:BLIM 01 PULMONARY DC.BOLISM ?l Ir I CASE 21.. I. L. - lhite, married, female, aged 50. Hospital :number 44671. Entered 8/10/33. Died 8/15/33. Clinical diagnosis: I ~ertension. Auricular fibrillation and decompensation. Post-mortem diagnosis: · Cardiac bJpertropby and dilatation. Cardiac infarction. Ml'ocardial fibrosis. Infarction of lung. Chronic passive congestion of k:1dlle79 and liver. Clinical evidence of thrombosis and embolism: Hone. Post-mortem evidence of tbrombosis: .A. mass of ante-mortem tbrombus one centimeter in diameter we.a found in the tip of the left ventricle over an area of infarction.

Poat-mortem evidence of pulmonaey embolism: · .A. 7 X 10 cm. infarct was found in the left lower lobe. It was broken down and jell7-lika in consiatenc7. On opening the pul­ mona.17 artery the thrombus causing the infarct was found. There were several amall infarcts in the right limg. Evidence of circulatoey failure: Clinical -- !wo months prior to entrance the patient began to have attacks of tachJ'cardia with d7spnea and orthopnea and swelling of her feet and ankles. bacerbation two weeks before entrance with aevere pain across the upper abdomen which •seemed as if it pre­ vented her from breathing•. On plvaical examination the heart was found to be considerabl7 enlarged, breathing was difficult, and there were re.lea in both bases. '.l!he heart was fibrillating, and the blood pressure was 198/122. Poat-mortem - The heart was considerably enlarged and weighed 500 grama. The trieuspid ring ea.sil7 admitted five fingers, indicating considerable dilatation. 'There were several •mall infarcts in the walls of the right and left ventricles and in the sept'WD. The coronary vessels on gross examination showed little change, but microscopically the blood vessels were found to be of small caliber and to show considerable intimal proliferation. Corresponding intimal proliferation was found in the blood vessels of the kidne7.

Comment: .A. possible source of tbe embolus 1'&8 not found. This is another case ot pulmonary embolism associated with cardiac failure. PROBLIM OJ PULMONARY EMBOLISM 72

B. c. - White, married, female. aged 59. Hospital immber 44820. :lntered 8/23/33. Pan-lo'aterectoll\Y (apiDal. novocaine anesthesia) on 9/6/33. On 9/15/33 the upper one-third of the wound, which bad broken down, was autved after an extruded loop of bowel was repla~ed. Died 9/17/33. .

Clinical diagnosis: .ldeno-carcinoma of uterue. Poat-mortem diagnoaia: A.deno-carcinoma of the uterus. Paralytic ileus. Pelvic thrombosis. Infarction of l'ang. Duodenal ulcer, healed. Clinical evidence of thrombosis and emboliam: Bone. Post-mortem evidence of thrombosis: !here were many thrombi in the veins of the pelvia. .l thrombus in the left internal iliac vein extended into the interior vena cava almost to the renal vein.

Poat-mortem evidence of pulm:>nary emboliam: The main branches of the pulmonary artery contained a J1W11ber of small masses of ante-mrtem thrombi. Small masses were lodced deeper in the lUDg t iasua causing infarct ion which had gone on to earl7 ga.D«J."ene. lvidence of circulatory failve: Clinical -- Swelling of ankles with aome dyapnea on exertion. Blood pressure was 220/120. Poat-111Drtem - The heart weighed 440 grams. !he left ventricle meaaved 25 to 28 ma. in thickness. Comment: !his case presenta evidence of earl7 circulatory failve. Thia factor with the additional factor of prolonged bed rest in an extremely ill patient probabl7 accounts for the pelvic thromboaia with metastases to the lmigs. ------

PROELD 01 PUliMORA.RY EMBOLISM 73

M. JI. -- White, female, aged 13. Hospital n'DlBber 47234. Jntered 6/3/34. Died 6/24/34. Clinical diagnosis: Bacterial endocarditia. Poat-mortem diagnosis: Subacute bacterial endocardit is. tnfarct of lung. Infarcts of apleen. lllmbol1c nephritis. Broncho-pne'UDIOnia. Clinical evidence of thrombosis and embolism: There were several attacka of acute abdominal pain attributed to various causes until it was found that the patient had a splenomegal7 and that her heart was bad. Post-mortem evidence of thrombosis: Numerous old and recent infarcts of the spleen. There were thrombi in several of the , although these did not com­ pletel7 occlude the vessels. The left auricle showed a mass of warty vegetations on the wall immadiatel7 above the mitral ring. Warty n:asses of soft reddish material were found attached to both mitral cuapa. There was a l cm. infarct in the -.11 of the left ventricle. The right aide of the heart was entirell' normal in appearance.

Post-mortem evidence of pulmonary embolism: J. huge long infarct was present in the periphe?7 of the right lung. Bo large masses of thrombus were found in the palmona.17 artery.

~vidence of circulato17 failure: Clinical - On admission to the hospital there was a palpable thrill over the cardiac area. The were regular with onl7 an occasional extrasystole. !here was a very- rough marnmr replacing the first sound at the apex. J. gallop rqtbm was noted. at the base. :Blood pressure was 90/54. The fingers were cyanotic. X-ra:; - Cardiac enlargement apparentl7 involving the right heart, and slight passive congestion of the lungs. Post-mortem -- Tbere was some degree of passive congestion of the j lunge. '!here was partial occlusion of several of the coronary branches due to thrombi. There was a l cm. infarct in the left ventricular wall. Vegetations of suba.cute bacterial endocarditia were f'crund on the mitral cusps, and on the endocardi'Ulll of the left auricle and ventricle. There was extensive fibrosis through the cardiac musculature. · Comment: J. case of aubacute bacterial endocarditia showed at autopa7 evi­ dence of' infarction in s7stemic and pul.mona17 arterial a;ystema. !he former can readily )e regarded aa em'bolic from the lesions in PROBLAi 0., PULMONARY EMBOLISM 74 the left heart. The latter are more difficult to interpret. but were proba.bl7 metastatic from venous thrombi which developed after the onset of cardiac failure. PROBLIM OJ PULMONARY IM]l)LISM 75

CA.SI 24.

J. K. -- lhite. married. male. aged 52. Hoapi tal number 48252. Entered 9/25/34. Died 10/17/34. Clinical diagnoaia: Diabetes mellitus. Blood sugar on entrance was 216 mg. 'f,. llf .P.B. on entrance was 58 mg. 'f,. Poat-mortem diagnosis: Card1ac b1pertrophT. Infarct of heart D11Scle. Coronary thrombosis. Uremic pericarditia. Subacute glomerular nephritis. lqdrothorax. P'2lm:>nary edema.

Clinical eTidence of thromboaia and emboliam: llfone. I Poat-mortem evidence of thrombosis: Several masses of ante-mortem thrombus were attached to the wall of the left auricular append.a&•· !here was a 9 X 6! cm. infarct l at the left apex with an attached liquified 1111ral thrombus. Poat-mortem evidence of pulmonary embolism: !here was a small infarct in the ~t lower lobe. hidence of circulato17 failure: Clinical - There was a marked d1aatolic murmur best heard at the apex. Swelling of ankles and acrot'Dlll which. however. was not attributed to cardiac pathology. Bo pain in the cheat. Post-mortem - !he heart weighed 430 grams. There was a large left ventricular infarct. with a correaponding coronarJ' thrombosis. '?here was marked acleroaia of the coronary arteries. Uremic pericarditis. .A.acitea. .A.nasarca. Comment: Only a amall infarct in the right lower lobe was found as evidence of pulmona17 embolism. The DIU'al thrombi. which were all found in the left heart. would not account for the infarction. J'ormation

of a thrombus in the Tenous circulation. with embolism to the lUDg9 mq be postulated on the basis of cardiac failure.

) ... PROBI.JBM OJ PULMONARY !JeOLISM 76

CASJI 25.

J. B. - lhUe, single, male, aged 39. Hospital n'Wllber 48608. :Sntered 11/8/34. Died 11/28/34. Clinical diagnosis: Myocardial decompensat ion secondary to eoronaey en.darter it is with thrombortia.

Post-mortem diagnosis: Cardiac infarct, left ventricle. Cardiac hT,pertroph7 and dilatation. :Broncho-pneumonia, right lower lobe. Chronic passive congestion of ltmga and liver. Small infarcts of lungs. Small infarcts of left kidney. Clinical ertdence of thrombosis and embolism: Bone, ucepting coronary thrombosis. Post-mortem evidence of thrombosis: Cardiac infarct in left ventricle associated with a large mural thrombos. Post-mortem evidence ot pul.IIX)nar7 embolism: A. anall mass of ante-rmrtem thrombus was f01llld in a ama.11 branch ot the pulmona.17 artery in the middle lobe of the right lung. Small masses of ante-mortem thrombus were found in association with infarction in the lower lobe of the left lung. :Svidence of circulatory f allure: Clinical - Patient was well until 18 rmntha before entrance to the hospital. Be had had several attacks characteristic of cor­ onary arter,.. occlusion. Coq>lained of ahortnese of breath and wealaless on exertion. There was coughing and spitting of blooq aput1llll with the first attack. On entrance there was a marbd orthopnea. The heart ah.owed extra systoles; rate was 120; blood preas'tl1"e was 102/?0. fhe heart waa rmderatel7 enlarged. X-raT -- Passive congestion of l'Ullg fields. Cardiac enlargement with preponderance of the right heal"t. Poat-mortem -- !he heart weighed Sa> grams. !he coronaey arteries showed severe atheromatoua change, with coq>lete occlusion bJ' atheromatous plaques of the right and left coroJ1817 arteries. ~re was a 9 X 9 cm. infarct in the posterior wall ot the left ventricle. with marked thinning of the wall. 'l'bere waa a large recent infarct on the anterior wall, with an attached large mral thrombua. Comment: !hia caae ahowd a congestive heart failure due to coronaJ7 arteey occl'usion. .A. probable s012rce of the pulmonarT embol1 was not found at autop97. PROBLJIM or PULMOHlRY IllMBOLISM 77

OAs.I 26.

H. .., • -- l'h.ite, married, female, aged 26. Hoapi tal number 48806. ~tered 12/1/34. Died 12/19/34.

Clinical diagnosis: Renal insufficiency with right b7dronephrosia. Oe.rdiac insufficiency with b1pertension. Mutiple thromboses with infarctions of l'mlg, spleen, and left lowr leg.

Post-mortem diagnosis: Old wcnephroaia, right lddne7 • .A.rteriolar sclerosis, left k1dne7. Cardiac ~ertropb1' and dilatation. Kural thrombi in right auricle, right ventricle, and lett ven­ tricle. Pulmonar)" embolism with infarction. lmbolus in . Infarcts of spleen and kidne7. Healed duodenal ulcer. Cholesteroais of gall bladder.

Clinical evidence of thrombosis and embolism: ..,our days after entrance the pat tent complained of mderate pain and distreaa in the cheat. She began the next dq to cough up some blood-streaked aputum, particularl7 in the eveninga. Ralea were beard in both bases. !hirteen ~s after entrance the patient began to ceq>lain of swelling and pain in her legs. On examination the legs were found to be cold and n:wnb, c7anotic, and swollen. The s)'Jlptoma grad'Uall)" progressed to the time of her death.

Post-mortem evidence of thrombosis: There wre Jlllll"al thrombi in the right auricle and in both Tentricles. There were numerous llDBll thrombi in the small veins of the pelvis. !be aorta was obstructed b)" an ante-mortem throm­ bus beginning about 2 cm. below the renal arteey.

Post-mortem evidence of pulmonaey emboliamr There was almost complete consolidation of the lower lobe of the right l"UDg, and the corresponding artery to the right lower lobe contained a large mass of ante-mortem thrombus. Snall ante-mortem thrombi were preaent in the amall branch.es in tbe left lung. lvidence of circulator)" failure: Clinical - Sh months ago, after the birth of her laat child, the patient had "high blood preen.re, faat pulse. and wa.a blown up like a barrel•. Orthopnea for pa.at six months. On pb7aical examination there waa quite marlmd cardiac enlargement to the left demonstrable. There was a gallop rh7thm. Heart rate wa.a 96; blood preen.re was a:JO/l&J. There we.a onl7 slight edema ot the ankles. X-rq - Gross cardiac enlargement involving primril7 the left ventricle. lvidence of aacitee. PROBLllM OF PULMONARY JMB)LISM 78

Post-mortem - The heart weighed 500 grame and meaaured 15 X 11 cm. There were mural thrombi in the right auricle and right and left ventricles. The mitral ring admitted three fingers easily-. !he muacle of the left ventricle was aoft and measured up to 25 mm. in thickness. Comment: Thrombi were found in the pelvic Telns and in the right auricle. :Sither JDa1' have been the source of tbs pulmona.ry emboli. A recent thrombus was alao found in the aorta, and smaller thrombi bad pro­ babl7 previousl.7 lodged in the arteries auppl7ing the legs, to account tor the clinical s71D.Ptom1 of arterial occlusion; there were also infarcts of the spleen and lddne7. !hrombi were foimcl in the left auricle and ventricle, and it was probably- from one or both of these sites that the qatemic embol1 originated. P.ROBLIM OJ PULMONARY EMJ30LISM 79

CASE 27. L. X. -- lhite, male, aged 2f. Hospital number 37979. Entered 2/l?J:J/32. Died 2/21/32. Clinical diagnosis: OateoJl'.l1'el1tis of right femur. Post-mortem diagnosis: OsteQll\Y'elitis of right femur. Infarcts of l"llJlg • .A.bscessee of lung, heart, and kidne7. »roncho-pneumonia.

Clinical evidence of thrombosis and emboliamt None, excepting the osteomyelitis, which might give rise to a localized thrombo-pblebitie. Post-mortem evid.ence of thrombosis: Bone. Poat-mortem evidence of pulmonaey embolism: Infarcts in lungs, some of which were purulent, and measured. l to 3 cm. in diameter. lvidence of circulatorJ" failure: lione. Comment: Following the onset of oateoJIG"el1tis, infected emboli probably from the site of infection, reached the lttn«s to set 'l2p metastatic infarcts and abscesses. PROBLIM OF PULMONARY EMllOLISM 80

CASE 28.

Y. Y. -- 1'hite, a ingle, male, aged 17. Hospital n'UDlber 38969. Entered 5/12/32. Died 5/13/32. Clinical diagnosis: Carbuncle of the neck. Septicemia. Blood culture poaitiTe after twent7-tour hours for Staphylococcus aureus. Broncho-pne'UDlonia.

Poat-mortem diagnosis: Carbuncle of the neck. Multiple lung abscesses. Infarcts of lag. Broncho-pneiunonia. Infected thrombi of Jvgular vein.

Clinical evidence of thrombosis and embolism: Marked edema was noted over left side of neck and scalp w1 th n188roua small areas where the scalp had broken down.

Post-mortem eTidence of tbromboais: The left Jugular vein shows a few bits of' very soft grq thrombi.

Post-mortem eTidence of pul.m11&17 embolism: Small thrombi in tbe pulmonary arterial branches. Small infarcts andabacessea of the lungs.

~vidence of circulatory failure: l'one.

Comment: Infected thrombi in the left J'1g'U].ar vein gave rise to emboli which lodged in tbs pulmonary arterial branches causing infarction and abscess formation. PiOBLIM OF PULMOlWlY IM:BOLISK 81

I. P. - lb.ite, female, widow, aged 71. Hospital number 39031. lntered 5/18/32. Died 5/19/32. Clinical diagnosis: Infected upper lip with cellulitia of face and neck. Septicemia. Blood C1llture was positive for Stapbylococeua aureua. Poat-mortem diagnosis: .A.bacess of upper lip with extension to face. Infected thrombosis of right Jugular vein. Pulmna.17 infs.rct ion.

Clinical evidence of thrombosis and embolism: Bone described in record.

Poat-mort• evidence of thrombosis: Infected ante-mortem thrombi were found in the veina of the face and in the right Jugular vein.

Post-mortem evidence of pulmonat7 embolism: . Both lungs showed infarcts ra?1ging from ~ i to 5 cm. in diameter. J.t least some of the infarcts had undergone abscess formation. Small ante-mortem thrombi were fo"Ond in the corresponding arterial branches.

Evidence of circulato?'J' failure: Bone. Comment: Dr. J. P. Tollman: •'?be i111Ediate cauae of this woman's death ia the abscess of the '\1pp8r lip extending throllgh the veins of the face. One of these veins stood out prominently and ante-mortem thrombi were remowd from the right l'UgUlar vein.• !he infected thrombi in the facial and right J12gU].ar veins were the probable sources of the metastatic pulmona.17 thrombosis which gave rise to p1ilmona17 infarction and abscess formation.

J - ----~---~------

PROBLD4 01 PULMONARY :lD.m>LISM 82

CASE 30.

H. C. - White, married, female, aged 22. llo•P.1tal number 40729. Entered 9/28/32. Deliver,y 9/29/32. Died 10/5732.

Clinical diagnoaias Diabetes mellitus. Diabetic coma. Blood a'Cgar was 186 mg. "· NPN was 60 mg. "· Pregnanc7, six montha. PJ'elonephritia. Inevitable abortion, 9/29/32, with delivery of a dead macerated f etua. Broncho-pneumonia. l Parametritis. i 1 Post-mortem diagnosis: ~ Atrophy of pancreas. Broncho-pne'WDOnia • j .A.cute vegetative endocarditia • I .A.bscessea of lung, lddn97, and broad ligament. Infarct ~ lllDg, left. Hemorrhage and thrombosis of uterine wall. Pelvie thrombosis•

Clinical evidence of thrombosis and embolism: Bone.

Post-mortem evidence of thrombosis: There was a sma.ll vegetation about 3 n:m. in diameter on the anterior cusp of the mitral valve, with no associated destruction of the valve cusp. The uterus was enlarged, discolored, and filled with clotted blood. There was thrombosis extending into the vessels of the wall. Several thrombosed veins were encountered 1n the broad ligament, and in one of these purulent material was found. Post-mortem evidence of pulm:>na?7 embolism: There was a 3 x 4 cm. infarct in the left lower lobe; it was semi-flu.id in consistenc7 due to infection.

Evidence of circulat0?7 failure: Poat-mortem -- There wa.a a mitral vegetative lesion, but no myocardial change wa.a found. !he heart was normal in size.

Oomnent: '1'he mitral vegetative lesion was a possible som'ce of the abscesses in the lddne7. The infected pelvic thromboses were the probable source of the infected infarct in the left lung and also of the lung abscesses. PROBLEM OJ' PULMONARY DmOLISM 83

CASB 31.

M. S. -- White, aiDgle, female, aged 24. B.oapital n'Ulllber 43130. Entered 4/5/33. Died 4/2/J/33.

Clinical diagnosis: ..l ~ Pansinuaitia • Otitia media. l Chronic glomerulo-nephritis. !erminal uremia.

Post-mortem diagnosis: I Left mastoiditis. ! .lbscesaea of lllng, liver, kidne7, and heart. Broncho-pneumonia. Acute glomerulo-nephritia.

Clinical evidence of thrombosis and embolism: Bone.

Post-mortem evidence of thrombosis: In the left lateral sinus no large thrombus was present, but imnediatelr ad,lacent to the mastoid a small ma.as of granular material was found firmly attached to the lateral wall of the sinus. Some of this material wa.a rather friable and broke off eaail7.

i Post-mortem evidence of palmon&I7 embolism: 'l' ! Left limg -- .l mass of ante-mortem thrombus about 3.5 cm. in l \ length and 6 mm. in diameter wa.a found in the main branches of the pulmonary artery. Similar very small masses were fo'll!ld deep within the lung tiBB'll8 and in association with these were aharplf delimited wedge-shaped areas in which the lung was solid and Yer7 dark in color. !here were several associated absceases. Right limg -- .l few ante-mortem thrombi were found in the smaller pulm>nary branches with corresponding areas of infarction and abscess formation.

:IYid.ence of circulatory failure: Bone.

Comment: In this case a left lateral sinus thrombus had undoubtedl7 been present, and wa.a the probable source of the pulmonary embol1, which, because the7 arose from a septic source, gs.Te riee to intarctiona which showed abscess formation. The small a'bsceeaea in:tbe·ether organa in the s7atem1c circulation were probably on the basis ot a bacteremia from the same source. 84

CASE 32.

B. D. - 1h1te, female, aged 2. Hospital Dlllllber 44083. lntered 6/2JJ/33. Died 6/Zl./33. Clinical diagnosis: J'uruncle, forehead.. :leysipelaa. Post-mortem diagnosis: hroncle, forehead. Cavernous sinus thrombosis. Blood plates from cultures taken at autops7 were positive for StaphTlococcus aureus. Meni:ngi t ia. Abscesses and infarcts of lungs. Broncho-pnelllllOnia.

Clinical evidence of thrombosis and em.boliam: :lone.

Post-mortem evidence of thrombosis: Purulent material and ante-mortem thrombi were· f aand in the left cavernous sinus with extension to the circular sinuaes and alight involvement of the cavernous sinus on the right.

Poat-mortem evidence of pulmonary embolism: There were several 11111all recent infarcts in both lUDga, some of which had broken down to form abaceaaea.

Evidence of circulato17 failure: Bone. l Coument: !he infarcts of the lUDg were infected and ahowed abscess formation. !be origin of t:he emboli causing the infarction .,..,. be postulated as the cavernout ainua where a paralent thrombotic process was l toimd. I., l '~

i i PROBUM 01 PULMONARY lllMBOLISM 85

CASI 33.

D. c. -- White, female. aged 8. Hospital number 48341. Entered 10/5/34. Right radical mastoidact01D7 (gas-ether anesthesia) on 10/6/34. Died 10/6/34.

Clinical diagnosia: Bilateral chronic otitis media. Acute mastoiditis, right. Lateral sinus abscess, right.

Post-mortem diagnosisr Radical mastoidectorq cavity, right. Lateral sinus thrombosis, right. Inflammation of the dura mater. Multiple amall infarct of lungs. Broncho-pneumonia. Cloud;v swelling of liver and ltidne79. Infectious hYPerplaaia of spleen.

Clinical evidence of thrombosis and embolism: Symptoms siJggested a right lateral sinU8 thrombosis complicating the right maato1d1t1s. fobe7-.A1'er test was positive. At operation a anall sinus was found in the right cavernous ainua through which foul smalling pus escaped.

Poat-mortem evidence of thromboaist Bo definite thrombus was found in either lateral sinus at autop117, but some granulations were noted in the angle of the right lateral sinus. !he lugular bulb on the right was filled with fairly firm ante-nortem thrombus.

Post-mortem evidence of pulmonary embolism: The pleural surfaces of the lunge were spotted with 1118.DY' brown areas, triangular in shape, extending into the lung substance, and measuring up to 1 mm. in diameter. On microscopic examination the small infarcts showed considerable inflamnato!7 reaction.

Evidence of circulatory failure: Bone.

Comment: A chronic ma.stoiditis resulted in eventual perforation of the right lateral sinU8 with extension of the suppurative proceaa into the sinus. Small infected emboli, brealdng loose, gave rise to multiple pulmonary infarctions which would have formed frallk abscesses if the patient had lived longer. PROl3LIM 07 PULMONARY EMBOLISM 86

C.AS3 34.

C. .A.. -- White 1 married, male, aged 52. Roapi tal mmber 40862. lnter~d 10/8/32. Died 11/1/32.

Clinical diagnoaie: Duodenal-colic :f'ietula (X-ra7). Secondar7 anemia.

Post-mortem diagnoaia: Carcinoma. of colon involving liver and duodenum. Thrombosis of' left external iliac vein. Palmonaey· embol iam. Pulmona17 infarction. Pulmonary edem.. Broncb.o-pnel1Dl0nia.

Clinical evidence of thrombosis and embolism: !welve day'e after admission the patient developed a sudden severe pain o'Yer the liver area, and :f'o'Ulld it ha.rd to get his breath. Post-mortem evidence of' thrombosis: Several ante-mortem thrombi were :f'01md in the left external iliac vein.

Post-mortem evidence of pulmonary embolismt Right lung -- J. number of' thrombi were firmly attacbed to the walle of tbe pulmo~ry arteries, most noticeable in the lower lobe. The deeper thrombi appeared older, so that the picture was that of' a retrograde thrombosis. Left lUDg -- .A. few small thrombi were fonnd.

lvidence of eirculatOT'J" .failure: Bone.

Comment: !here was no very definite clinical evidence of cireulator7 fail­ ure in this caee to suggest an explanation of the thrombosis of the left external iliac vein. !he heart was negative on path­ ological examination. Prolonged bed rest in a debilitated individual suggests an explanation of the formation of the thrombi, with embolism and infarction of the l'angs. PROBLIM or PULMONARY Dm)LISll 87

CASI 35.

H. S. -- White, married, uele, aged 65. Hospital number 41114. ~tered 10/29/32. Died 11/22/32. Clinical diagnosiet Cortical atroph7, etiolog not determined (encepbalogram). Post-mortem diagnosiat Diffuse cortical atrophJ'. fhromboaia of pelvic 't'81ne. Pulmonar)" infarction. Broncho-pneumon1a. Passive co:agestion of spleen.

Clinical evidence of thrombosis and eaboliem: Bone.

Poat-mortem evidence of thromboaist .A number of ante-mortem thrombi were found in the 't'81ns of the pelrlc wall.

Post-mortem evidence of pulmonar;y emboliam: Sall thrombi were found in the left lung with infarcts 1 to 4 cm. in diameter. Large emboli, occluding practicall)" all the principle •••••la, with infarction were found in the right lun,;. lilTidance of circulatOl"J" fail'uret Post-mortem -- Pasa1Te co:agestion of spleen. Comment: Botht:ng ver7 definite was :round to account for the occurrence of the pelYic thrombi which were the probable source of the pulmon­ ary emboli. PROBLIM 01 PULMONJ.RY EM130LISM 88

CA8 36.

J. G. - lh.ite, single, male, aged 68. Hospital number 41940. lntered 1/3/33. lspreasion of cataract, right e79 1/5/33. Died 1/14/33. Clinical d.iagnosia: Bilateral senile cataracts. Right indirect il'lg1linal hernia.

Post-mortem diagnosis: Thrombosis of pelvic veina. PulmoDa17 embolism with infarction. Gangrene of 112Dg, le~ lower lobe. Arteriosclerosis, generalized.

Clinical evidence of thrombosis and emboliBlll Jour days after operation the patient developed a a'Wlden severe pain 1n the left upper abdomen and cheat with d7apnea and pain on reapira­ t ion. !he abdomen was distended and rigid on the left aide. '!here was some limitation of motion on the left aide, especially at the base. .An enema gave considerable relief. Adhesive at rapping of left cheat also afforded some relief.

Poat-mortem evidence of thrombosis: Several ante-mortem thrombi 1n several of the deeper brancbea of the pelvic veins, particularl7 those to the muscles of the gluteal region.

Poat-mortem evidence of pulmona.17 embolism: Left l'U!lg -- llimieroua ana.11 infarcts in upper lobe. Gangrene of whole lower lobe with liquifaction and formation of a large ragged cavity. .A. large gra:y ante-mortem thrombus occluded all of the vessels to the lower lobe. Right lung -- Ho thrombi were f O'\lDd in art1' of the palmona.r;r arteries.

llvidence of circulato17 failure: Hone.

Comment: Dr. J. p. Tollman: •fhia is interpreted as being a pelvic throm­ bosis. Some of these thrombi became loosened and caused infarction of the left lower lobe of the lung. It subaeqmntly became gangren­ ous. The sudden death is interpreted as a maaive bemorrbage into this gangrenous 112Dg and pleura on the left aide. !he recent eye operation shows evidence of normal healing and ia onl7 indirectl.1 the cause of death 1n that it was necessary to keep him in bed for several daT• allowing the pelvic thrombosis to occur.• !he time of occurrence of the embolism was Ter;y definitel7 set by the clinical record as four ~ postoperative. PROBLIM 07· PtJLMOlWlY IMB>LISK 89

CASE 37.

G. S. -- White. married, male, aged 46. Hospital m:uaber 43768. Entered 5/?13/33. Laparotonv (apiDal anesthesia) 5/31/33. Died 6/1/33. Clinical diagnosis: .A.cute cholec7stitis. Possible np7ema of the gall bladder. Poat-mortem diagnosis: .A.cute pancreatitia with retroperitoneal hemorrhage. Jat necrosis of mesentery. Broncbo-pne'WllOnia. Infarction of 11l!lg. Clinical evidence of thrombosis and embolism: Bone. Post-mortem evidence of thrombosis: None.

Poat-mortem evidence of pulmoDal'7 emboliam: ' Several ante-mortem thrombi were found lodged in the -.rioua branches of the palmoDa.?7 arteey, and in several plaeea large dark, rather aoft, infarcts were found to correspond with these emboli. Bvidenoe of circulatoey failure: tone. Comment: fhia case presents the finding of pu]JmDary emboli11111 and in­ farction with no demonstrable prlmry thrombus. !he marked prostration and consequent certain a111>unt of venous stasis which was probabq present 11117 have resulted in the formation of throm­ bi which either were overlooked at autops7 due to inacceaaibilit7 or were completel7 dislodged before death. fbe iq>ortauce of the acute pancreatitia aa a direct factor in formation of thrombi it would be difficult to estimate. PROBLEM 01 PULMONARY EMBOLISM 90

CASE 38. L. K. - White, married, male, aged 56. Hospital nwnber 45153. Entered 9 /64/33. Died 10/Z5/33. Clinical diagnosis: Bo definite clinical diagnosis waa na.de. Stoola were negative for protozoa and parasites on numeroUB occasions. X-rq - Sinus tracts were found 1n the hepatic flexure region and descending colon, extending off from the colon. Poat-mortem diagnoaia: .A.mebic colitis with perforation. Peritonitis. Pulmma17 throm'boala. Lobar jlleWmnia. Broneho-pneumonia. '!hromboaia of the left iliac vein.

Clinical evidence of thrombosis and embolism: J'one.

! Poat-mortem. evidence of thrombosis: Thrombosis of left iliac vein. f Poat-mortem evidence of pulmon&rJ' embolism: Left lung - The pulmoDary artery showed a thrombus rather firml.7 ! attacl:aed to the wall and extending into n'Ullleroua branches, but apparentl.7' without CODplete occlusion of aD1' except the smaller I diTI.sions. Right lmg - .A. similar thrombus waa found in the pulmonary I ...... 1 •• lvidence of circulatory failure: I J'one. f Co1111111nt: fhia patient was in the hospital for one month. During this I time he was ver.,. weak and unresponsive, 17ing veey quietl7 in I bed. It would appear, therefore, tbat staaia was a moat import­ ' ant factor which might account for formation of a venoua throm- I bosis with embolic paaaage to the lungs. · I ------

PROBLJM OJ PULMOnRY DraOLISM 91

CASI 39 •

.A.. M. -- 1'h1 te, married, tenale, aged '13. lJoapital number 48477. Entered 10/23/34. Died 10/29/34. Clinical diagnoaia: Jlaltgnanc7 of cecum with degeneration and abscess formation. Poat-mortem diagnosis: .A.denocarcinoma. of bod1' of uterus. Metaataaea to wall of abdomen and to periaortic lymph nod.ea • .A.baceas of wall of pelvis, right. ' Small embol1 in palm:>na.17 arteries (no infarcts).

Clinical nidence of thrombosis and em'boliam: Bone. Post-mortem evidence of thrombosis: llaD7 e-11 veil18 around the bladder and the uterus contained ante-mo rt em thrombi.

Poat-mortem evidence of pulmona17 embolism: .A.t the second bifurcation of the pu1mona17 arte1'J' to the right limg there was an ante-mortem thromba.a attached to the wall with no accompan;ring i:ntarction. There were aaller thrombi in the pul.mona17 branches to both lungs. Evidence of circulatory failure: None. Comment: Thrombi were found in the veins of the pelvis, and were the probable source of the ante-mortem blood clots found in the palmona17 arter7. Venous staaia in a prostrate :gatient is avg;.. geated. aa an important etiological factor. BO'flS Olf !rBllliAPllOSIS

It ia not the object of the writer to in.elude in the present dis­ cussion of the problem of pulmonary embolism a detailed consideration of treat•nt of the condition, yet a few remark& upon therapeuaia are perhaps tiuely in relation to what has gone before. .A. defective circulatorr mech­ anism has been emphasized as the one well recopised factor in the f orma­ t ion of venous thromboses. It has been pointed out that the present dq conception of the matter ha.a advanced little since the time of Virchow who first proposed the theory of circulatory ataaia in addition to blood changes aa the predisposing factors eaeential to formation of intra-vitem blood clots. Therapeuaia ha.a therefore' found its moat practical applica­ tion in the atteJl!>t to •intain adeqllate circulato17 tone in those cases wherein it is thought possible or probable that venous thrombosis and palmoDaJ7 embolism mq occur.

David (W.,itera, 7Q) has euphaeised these considerations, and aqa:

•l:Jntil more definite facts are known concernbtg the •ehanica and chemistry of blood coagulation, our efforts mast be aimed at removal of f actora which preclispoae to thrombosis.• .A. perusal of the literature reveals ·in geural two methods of approach in propbTla:da of thrombosis and pulmona.J'7 emboliam:

!he first, and older aethod deals chiefl7 with the individ'U&l patient.

!he clillic1an attenpts to recognize earl.7 signa of thrombosis. and. watches for evidence of amall po.l.moDarJ' emlaolic accidents which mq be premonito17 of larger emboli to follow. Having previoual7 carried out the wll known general methode for prevention of thrombosia and emboliem (freqiient change in position of the bed-ridclen patient, preeerT&tion of free 111Dbilit7 of tbe 93

cheat, encouragement of earl.7 S111tematic enrciae atter operation, avoid­

ance of tight bar.ldagea, dail.7 elevation of the foot of the bed aa a mech­ anical method of increaa ing the venous flow from the dependent pelvie re• gioa:;, and so forth), an e:ractl.7 reverse proceedure ia now instituted, and the guiding principle of managemant is rest mt onlJ" to the part where the trouble is manifest but to the entire bociT. (Romana, 35 ; Hunt, 37 ;

Rabinowitz and Holtzman, 57: Vietor, 68; 'falters, 70).

!he second mathod of propb1-laxis of thrombosis and pllllll)n&rJ" emboliem la more or leas experiJDBntal, and deals with groups of patients. It ia an attempt in application of some of the experimntal knowledge of blood chagea in thrombosis unearthed in recent 7eare; and is furtbermore an attempt to appl.7 this knowledf;e to groups of patients, since pulmon&J:'1'. embolism ta ao verr often unpredictable in individual patients. Perhaps the most notable attempt is that of 'falters (?O), who, 'b7 the routine administration of tqroid extract to postoperative patients, has apparentq been able to reduce to a minimam the postoperative incidence of fatal pulmonaJ7 embolism at tbe Ma;ro Clinic. Mills (49, 50, 51), and Bancroft, ltugelmasa, and Stanle7-Brown (3, 4 ,5) have foimd that 'b7 va1'1'ing the protein content of the diet the coagulabilit7 of the blood can be con­ trolled at will, and the latter have emplo;yed this knowledge in manage­ unt of clinical cases •

.A. paper on the subject of pulmoDa1'7 emboliem would hardly be complete without mention of the Trendelenberg operation. .A. few brilliant successes ha.Te been achieved 'b7 this method of managemaat of cases of naaaive pul• lll)Da17 embolism (ltirachner, Merer, Gint z, Crafoord., and l117strom). The operation ta possible because in IDBDT cases occlusion of the arterial lumn b7 an embolus aq be so far from complete tbat the circulation ia PROBLEM OP PULMONA.llY liMBOLISll 94

carried on for some time, although under a mechanical diaadYaD.tage that

ul.timatel.7 leads to death.

Runt (37) 881'8 that since it has been shoWD to be possible to reacroe a patient from the extremit7 of an otherwise fatal pul.moneJ7 embolism, an obligation is laid upon every hospital to have suitable instruments avail­

able and a member of the staff speciall.7 qualified. lhen a case is in imninent danger of a massive embolism a suitable operating room, instruments, patient, surgeon should be in a1JCh close relationship that the operation can be begun almost inatantl7. Of the lJniversit,. Hospital cases of massive pul.monar)' embolism. at least two (cases 1 and 5) would have been excellent candidates for the Trendelenberg operation, bad the neceaaa17 facilities

been available.

Bunt concludes: "The difficulties in the 1'81' of such a coordination

and the poaaiblitiea of an error in di8811o&1a are obvious. .A. a1JCcesaful

operation ia likel7 to remain the rare achievement of a watcbful~ fearless, and capable surgeon. .ls N78trom well sqa, 'It is upon prevention that

~e have to place our hope of being able to defeat at some future time one of the mat clistreaaing coq>lications with which, after the Tictoriea won

· bJ' the introduction of antieepties, aurge17 has still to wrestle.'" 1. !hirt7-nine necropa7 caaea of pulmona17 embolism were seen in the Un1versit7 Hospital in a three 7ear period (1932 to 1935) in which 309 autopa1ea were performed. 2. !he percentage incidence was 12.6 for total caaea of pulmoD8!'7 embolism. 10.4 for caaea of •bland• pulm>DaZ'J' embolism. and 2.6 tor caaee of 118811ve (fatal) pulmonaey embolism.

3.; ' !went7-on.e of the thirt7-n1ne ca.sea showed definite cardiac pathology. llelative!T few of the cases of massive pulnonary emboliam and of poet parl'Wll and postoperative pulmoDaJ7 embolism showed cardiac pathology; and a relativel7 large proportion of the medical cases showed cardiac patholog.

4. .Althouch the aeries of Un1verait7 Hospital cases studied was small, tbe findings were comparable to those cf other hoapi tale and clinics.

5. '?he general problem of pulmonaJ7 embolism is discuaaed with special reference to the cases seen at the Univerait7 Hospital.

6. .Attempt was not made to diacuas treatment of pulmoDal7 embolism in detail. However. it is emphasised that prop}vlactic measures will be the chief means of approaching the problem. SeTeral of the University lloapital

, cases of massive pulmnar7 embolism would han been excellent candidatea for the Tre:ndelenberg operation. 7. Atteupt will be made in the Department of Patholoa at the UniTerait7

Boapital to carry out a atud7 of the relation of infection. to the occurrence of thrombosis and pulmonar7 embolism of the so-called •bland• t1'P8• :BIBLIOGBAPBT

l. illen. :I. T. 1927 - Changes in the Bload hllowing Operation. Arch. S1Jrg. 15: 254-264.

2. Armitage. :I., Pickering, J. w•• and Mathur, S. N. 1932 -- !he Inception of :Blood Clotting. :Biochem. Jour. 26: 853-864. 3. :Bancroft, F. w. 1931 -- fhromboaia and lmboliam. Jour. Med. Soc. New Jerae7 28: 619-626. 4. Bancroft, 'I. w. • l'.11gelmass, I. !T., and Stanlq-Brown, l4. 1929 -- Bvalua.tion of Blood-Clotting Factors in Surgical Diaeaaes. Ann. Surg. 90: 161-189.

5. Bancroft, 'I. •~ and Stanler-Brewn, M. 1932 - Postoperative !hromboaia, !hrombophlebitia, and llmbolism. Surg., Gyn., and Obst. 54: 898-906.

6. Banet, 1f. D. 1924 - !hromboaia and :lm.boliam. Canad. I. A. J. 14: 129-132. 7. Jankoff, G. 1934 - fhromboaia, :lm.boliam, and !heir !reatmant. Brit. Med. Jovr. 1: 189-190. a. Barker, •••• 1935 -- Axillary !hrombophlebitia Caused b7 Strain or llftort. Proc. Staff Meet. Mqo Olin. 10: 156-160.

9. :Bartela. :I. C. 1933 - l'atal Postoperative PulmoDa.%7 :lmboliam. Minn. Med. 16: 409-416.

10. :Beattie, J. 1932 - Pblmonary :lm'boliam in llelat ion to Preg.nanc7. Lancet 2: 1105-1107.

11. Belt, !. H. 1934 - Pul.mona?"T Embolism. Canad. M. A. J. 30: 253-.255.

12. Belt. !. H. 1934 - Thrombosis and Pulmna?"T lmboliam. J.:m. J. Path. 10: 129-144. ------

PROBLEM OF PULMONARY DCBOLISM 97

13. Bernheim. B. M. 1929 -- 7atal Bmboli from !fbromboaes of Great Blood Teasels: The Concealed !hromlraa. South. Med. Jour. 22: 464 466. 14. Brock. R. C. 1933 - Postoperative "fe:no'U8 'l'hromboais and the Platelet Count. Lancet 1: 688-690. 15. Brown, G. I. 1927 -- Postoperative Phlebitis. Arch. Surg. 15: 245-253.

16. Bann, 1'. H. 1934 - TSgariea of Veno,. Thrombosis. Ohio State Med. J. 30: 159-162. 17. Cabot, ll. C. 1933 -- !bree Cases of Postoperative J'atalit7• ••• JJ:Jg. J. Med. 208t 2.59-265.

18. Churchill, I. D. 1934 - !he Mechant .. of Death in Mua1Te Pulmonary ~11-. Surg., G71l., and O'bat. 59: 513-517. 19. Conner, L • .L 1914 -- .A. Pulmona17 .A.ttack Shnlating Prhar7 Lobar Pneumonia, Caused b7 Pulmonary :lmbclism and Infarction from a Latent feD.OUB 'fhrombosia. Arch. Int. Mad. 13: 349-360.

20. Drinker, J:. R. and Drimr, C. 1:. 1915 - 7actora Affecting the Coagulation !ime of Blood. VI. fhe .:feet of Rapid ProgreasiTe Hemorrhage 11p0n the !'actors of Coagulation• .Am. J. Pb1'siol. 36: 305-324.

21. :la.rlam, 7. and ITana, 1'. H. 1928 -- '1'he Relation of the Blood Platelets to !hromboaia after Operation and Parturition. J. Path. and Bact. 31: 833-873.

22. :Ivana, J. .A.. and Paxon, J. 1932 -- Jlmboliam During Convalescence from Th.7roidAtctonv tor Toxic Goiter Oo~licated b7.A.uricular 7ibrillation. Wisc. M. J. 31: 464-465, 492.

23. 7arr, C. :I. and Spiegel, R. 1929 - Pulmonar,r Infarction and :&mboliam. .A.nn. Burg. 89: 481-511.

24. Gradwohl, ll. B. H. and Hiller, S. J. 1934 - !he Blood Platelet Count in Postoperative !hromboaia. J. Missouri M• .A.. 31: 392-395.

25. Gram, 11. C. 1930 - On the Platelet Count and BleediDg !ime in Diaeaaea of the Blood. A.rch. Int. Med. 25: 325-332• PRO:BLEM OF PULMONARY IMBOLISM 98

26. Haggart. G. B. and Walker. ..l. Y:. 1923 - The P.bTaiolog7 of Palmonary lmboliam as Disclosed b7 Q,uantitatbe Occlusion of the Pulmonary .Arte17• .A.rch. Surg. 6: 764-783.

27. Hall, G. m. and Ettinger, G. H. 1933 - An Experimental Stuq of Pulmonar,r Embolism. Canad. II • ..l. J. 28: 357-368. 28. Hamburger, w. w. and Sapbir, o. 1932 -- lmbolism Complicathlg and Simalating Cor0Da17 Thrombosis. Med. Olin. lt. .lm. 16: 383-403.

29. Hsnma,n' L. 1934 -- Sadden Death. :Bull. Johns Hopkins Hosp. 55: 387-415. 30. 1Jane7, B• ..l. and Levine, s . .A.. 1930 - ..l St'Ud.7 of Uninfected Mural !'hrombi. J. Med. Sciences. 180: 365-372. 31. Hegler, O. 1927 - .. On the Increase of !hrombosis and lmbolism During the Paet SeTeral Years. International Clinics 4 (Sar. 37): 1-5.

32. Henderson, •· 1. 1927 - Jatal PulmoD&l'7 a Statistical Review• ..lrch. Surg. 15: 231-236. 33. Hewlett, .A.. w. 1928 -- Pathological Phl'siologJ" of Internal Diseases. Pages 559-561. D. Appleton and Oompa.D1', Bew York.

34. Hirachboeck, J. J. 1935 - Paradoxical Bmboliam. .A.m. J. lled. Sci. 189: 236-239.

35. Homans, J. 1934 - fhromboaia of the Deep Teina of the Lower Leg, Ca1281ng Pulmonary •bolism. )Tew. Jlng. J. Mad. 211: 293-297.

36. Hosoi, I. 1932 - Pulmonary bboliam and Infarction• ..lnn. S'Ol"g. 95: 67-92.

37. Hunt, B. L. 1933 -- Postoperative !hromboaia and Embolism. Bew llng. J. Med. 3'8: 730-739.

38. Iampmeier, R. H. 1934 - 'fbromboaia of Main :Branches of the Pul.,nary Arteey. J. fhoracic Burg. 3: 513-524. PROBL'IM OJ PULMONARY EMBOLISM 99

39. Xaraner, lL ! • and .A.sh, J. JC. 1912 -- Studies in Infarction: II. lCxperilllental Bland Infarction of the Lung. J. Med. Rea. 2?: 205-224.

40. Kilbcmrne, ll. J. 1929 -- 'l!reatment of Varicose Veiu of the Legs. J. Am. Med. Assn. 92: 133)-1324.

41. Kuhn, J. X. 1929 -- Ca'tlllee of Increased Incidence of Thrombosis and lmboliam from 1924 to 1927. J. Am. Med. Aaan. 93: 499.

42. Lee, B.. I. , Minot , G. B.. , and Vincent, :B. 1916 - Splenectom;r in Pernicious .A.nemia. J. Am. Med • .A.ssn. 67: 719-723. 43. Lowenatein, P. s. 1924 -- !hrombosia of the .A.xillary Vein. J. Am. Med. .A.aan. 82: 854-857. 44. Macka7, w. 1931 -- !he Blood Platelet: Its Clinical Significance. quart. J. Med. 24: 285-328. 45. McCartne7, J. S., Jr. 1927 - Palmonar7 Embolism. .Arch. Pa.th. 3: 921-937.

46. Means, J. 11. and Ma.11017, T. B. 1931 -- total Occlueion of the Rtght Branch of the Palm:»nary .A.rte17 bT an Organized Thrombu.a • .A.:nn. Int. Med. 5: 417-427.

47. Me7er, .A.. W. 1930 - !he Operative !reatment of lmboliam of the LUDgS. Surg., G111., and Qbat. 50: 891-898.

48. Miller, B.. 11. and Rogers, 11. 1929 -- Postoperative Embolism and Phlebitis. J • .AJB. Med. Asan. 93: 1453-1456.

49. Milla, O• .A.. 1923 - ti'fect of 7ood Ingestion on the Clotting Time of the :Blood. J. Biol. Chem. 55: xviii-xix.

50. Milla, C• .A.. 1930 - Relation of Protein Diet to Thrombosis • .A.nn. Surg. 91: 489-491. 51. Milla, o• .A.. and Jlechelea, H. 1927 - SpecUic J>7namie Action of J'ood and Blood Coagalabilit1'• Soc. Bxper. :Biol. and Med. 25: 195-1.96~ ------~-~~- ---

PROBLEM OF PULMONARY EMBOLISM 100

52. :l7atrom, G. 1930 - Kxperiencee with the !rendelenberg.Operation for Pul.mona17 J:mbolism. Ann. Surg. 92: 498-532.

53. Pate7, D. K. 1931 - Injection !reatment ot Yaricoee Ye1Da and Its Bearing on the Proble• of !bromboeie. Lancet 2: 284-289. 54. PickeriDg. J. w. 1928 - !be Blood PlaBlll& in Health and Dieeaae. Pages 162-177. The MacMillan Co1Dpa.D1', Bew York. 55. Pickering, J. w. and Mathur, s. B. 1932 - The Bole of !issue Juices in Thrombosis. Lancet 2: 387-388.

56. Pigford, R. C. 1933 -- The Problem ot fhromboaia. J. Oklahoq K• .A.. 26: 184-189.

57. Rabinowitz, M• .A.. and ltoltzman, I. lt. 1934 -- !ha Jlarl7 Recognition of Peripheral Tenoua !hromboaie. B. Y. State J. M. 34: 973-977.

58. Reimann, IL .A.. 1924 -- !be Blood Platelets in Pne'UIDOcoccua Infections. J. hper. Med. 40: 553-565.

59. Rieckhoff, G. G. and Turcotte, V. J. 1933 -- Embolism of the PulllCna17 Artery. J. Mich. State M. S. 32: 95-97. 60. Rosenow, :I. c. 1927 -- .A. Bacteriologic St'Ud1' of Pulmo:Dar7 lmboliem. J. Inf. Dia. 40: 389-398. 61. Roaenthal, S. R. 1930 - Thromboeie and lmboliam. An J.nal.7aia of 1000 .A.utopaiea. J. Lab. and Olin. Med. 16: 107-118. 62. Rosenthal, S. R. 1932 -- !hromboaia and Jatal Palmona17 Embolism. Arch. Path. 14: 215-237.

63. ll'ODlOld, M. J. 1935 -- Blcperimental Pulmonar;y :lmboliam..laaociated with Venocl7aia • .A.rch. Sorg. 30: 685-701. 64. Shivers, G. C. 1933 - Pal.mona17 lmboliam from .lraenicala Injected Intravenousl7• .A.rch. Dermat. and S1J>h. 27: 901-922. PROBLIM OF PULMONARY EMBOLISM 101

65. Snell, J.. 14. 1927 -- !he Relation ot Obeait7 to Jatal Postoperative Plllmon8.17 Embolism. .1rch. Surg. 15: 237-244.

66. Steuer, L. G. 1933 - :lmboliam and Thrombosis of the Lal"ge :Branches of the PulmonaJ7 .1rter7 in Heart Disease. J. Lab. and Clin. Med. 19: 265-268.

67. Tho111U, H. 11. and J.lyea. B. 1929 -- Palmona.17 llmboliam J'ollowing Urological Surge17. South. 1184. Jour. 22: 737-745.

68. Vietor, J. A.. 1925 -- Clinical Considerations of Thrombosis and Embolism. .A.nn. Surg. 82: 193-198.

69. Walters, W. 1927 -- !he Suggested Use of ~oid llnract to Reduce the Incidence of Postoperative Embolism. Minnesota Med. 10: 25-28.

70. Walters, W. 1930 - J. Method of Reducing the Incidence of J'a.tal Postoperative Pulmonary Emboliam. Surg., G111., and Obst. 50: 154-159.

71. Wilson, L. ~. 1912 -- Jatal Postoperative Jmboliam. .inn. hrg. 56: 809-817.