CHAPTER 54 DEEP VENOUS : A Practical Review with Current Recommendations

Gerard V. Yw, D.P.M. Ielfrey E. Shook, D.P.M. Craig Sellers, D.P.M.

Deep (DVT) and pulmonary Most of the preventative measures against (PE) can be the most devastating post- DVT are performed in the . With the advent operative complications encountered by a surgeon. of economic-medical reform, hospital stays for both The incidence of is estimated medical and surgical patients will potentially be between 300,000 and 600,000 cases per year.' much shorter. This will have an effect on the deliv- Pulmonary emboli account for approximately ery and efficacy of prophylactic protocols against 100,000 fatalities per year2r and are the fourth lead- DVT. Even more alarming is the realization that ing cause of death in the United States.4 A large most patients still have significant risk factors after percentage of pulmonary emboli are silent,5'6 and discharge from the hospital. Although most throm- although fataliqr in symptomatic pulmonary emboli bus formation begins during or within 48 usually occurs in the first 30 minutes,2 four to eight hours after surgery, several studies have docu- thousand deaths a year could be prevented with mented that the development of DVTs can occur simple prophylaxis.2''i Most pulmonary emboli orig- well into the postoperative course.5" 5'z Kakkar inate from thrombosis within the veins of the lower observed that 23o/o of DVTs occurred between the extremity.5 Proximal iliofemoral thrombosis 15th and 25th postoperative day.t' Johnson accollnts for a higher percentaple of embolic events reviewed approximately 8000 total hip arthroplas- than does distal or calf thrombosis. Other signifi- ties and found that 36.70/0 of all fatal pulmonary cant sequelae from a deep venous thrombosis are emboli occurred between the third and fifth post- the pain and discomfort which may be experienced operative week.53 Recently, Trowbridge et al. at initial onset, and the possible development of followed 38 total hip arthroplasties monthly with post-phlebitic syndrome which occurs due to duplex ultrasound and venography for a total of valvular incompetence subsequent to thrombosis. three months. At the time of discharge from the Multiple orthopaedic studies have been per- hospital, patients were presumed to be thrombosis formed to assess the risk factors, prophylactic free after ultrasound or venographic evaluation. measures, diagnostic modalities, and treatment reg- Four of the 38 patients developed post-hospitaliza- imens associated with deep venous thrombosis of tion DVT; 2 of the 4 occurred during the first the lower extremity.T4' Other medical specialties postoperative month while the other two devel- have also noted the necessity for DVT prophylaxis oped during the second postoperative month.35 iz't: 'trnfl have shown a substantial decrease in the This finding may suppofi the recommendations of incidence of DVT when adequate prophylaxis is many orthopaedic surgeons who recommended implernented. Marshall states that all general surgi- extended, post-hospitalization coumadin prophy- cal patients undergoing major operative procedures laxis for trp to L2 weeks following discharge.lIl32'31'54 should receive peri-operative DVT prophylaxis.a6 A review of the major textbooks of surgery of However, it is clear that many patients who need the foot and ankle will reveal little if any discussion prophylactic measures do not receive them.aTaeln concerning the peri-operative prevention of deep one study, a review of hospitalized patients venous thrombosis.55 5' Because a majority of showed that only 320/o of the patients categorized in surgery performed on the foot and ankle is not the high risk group received appropriate protection considered major surgery, it would seem that foot against DVT.4' and ankle surgeons are relatively immune to the CHAPTER 54 275 complication of deep venous thrombosis. levels. \[hen evaluating all possible risk factors and However, major fusions, complex fracture repairs, applying the classification system used by Hull et and multiple osteotomies usuaily entail an opera- al., surprisingiy, many of the reconstructive surgical tive time of over tlvo hours, induction of general patients fall into the moderate and even the high anesthesia, the use of a thigh tourniquet, and some risk groups.65 (fable 2) type of postoperative immobilization of the opera- tive extremity. Certain reconstructive procedures of Table 1 the foot and ankle certainly qualify as major surgery and merit careful attention to additional RISK FACTORS FOR DWPE risk factors for deep venous thrombosis. This real- coupled with shorter hospitalization, an izalion, 1. Recent surgery (increased with orthopaedic aging public, and the need for postoperative immo- surgery) bilizatron, has convinced the authors to be more 2. Prolonged surgery (especially greater than 2 prophylaxis against DVT. aggressive with hours) 3. History of previous DVT RISK FACTORS 4. Inherited or acquired coagulopathies 5. Thorough assessment of the variables involved 6. Immobilization or bed rest with a specific surgery is first priority. Duration and 7. Short or long leg cast following major surgery. anatomical location of surgery, type of anesthesia, 8. Congestive use of a tourniquet, and postoperative immobiliza- 9. tion are all primary considerations in deciding 10. Age (especially greater than 55) whether a patient will need peri-operative DVT 11. Oral estrogen use prophylaxis. It becomes quite obvious that a 12. Serious burns patient undergoing routine forefoot surgery on an 13. outpatient basis possesses far less risk than a 14. Tourniquet use patient who is scheduled for a triple arthrodesis. Based on the analysis of the procedure, many foot (Modified from Baker and Bick6e) and ankle surgical patients will be eliminated from patients prophylactic consideration. However, in Table 2 who will have major reconstructive surgery of the foot and ankie, analysis of common risk factors will OF RISK FOR DWPE help place patients into low, medium, or high risk CIA.SSIFICATION groups for the development of thrombosis. Based on this classification, a decision on the need for HIGH RISK prophylaxis can be made. 1. Age >40 Many authors place all of the risk factors into 2. Prolonged Surgery one group (Table 1)'+'+s'i'r'ot however, it is essential to 3. Previous DVT or PE identify the common or primary risk factors for 4. Secondary Risk Factors* proper classification. The three most common risk 5. Hereditary or acquired coagulopathies factors for DVT among hospitalized patients are MODERATE RISK recent major surgery, 2ge, and obesify.a* Even 1. Age >40 though there is no scientifically proven mechanism, 2. Prolonged Surgery several studies show that increasing age, especially Secondary Risk Factors* greater than 55 years, predisposes the patient 3. LO\V RISK towards the development of D\rIi.2'46'18'ie'5e-6aA signif- icant number of the patients involved in foot and 1. Minor Surgery ankie surgery arc older than 40 years. Also, obesity 2. No secondary Risk Factors* *Risk is not an uncommon finding, especially in patients factors 5-t4 in Table 1 who have had a dysfunctional foot and/or ankle (Modified from Mer1i59) which has subsequently curtailed previous activity 276 CHAPTER 54

In some respects, major surgery of the foot Although less than 1,0/o of all fatal pulmonary and ankle may involve even more danger than pre- emboli are thought to originate from calf thrombo- dicted by any risk group analysis or classification sis, 20-30o/o of calf DVTs extend proximally into the system, due to the ambiguity of immobilization popliteal space. Kakkar et al. followed 732 postop- throughout the literature. Immobllization has not erative patients, and detected forty cases of deep been properly and clearly defined with regards to venous thrombosis; thirty-nine of these were con, foot and ankle surgery. Most definitions of immo- firmed with phlebography. Fourteen of the forty bilization actually are describing a non-ambulatory demonstrated small thrombi iess than five centime- situation. It is clear that a patient may be ambula- ters in length located in the soleal or tibial veins. tory postoperatively but stil1 have ar1 entire A11 of these underwent spontaneous lysis within extremity immobilized in a short or long leg cast. seventy-rwo hours, demonstrated by an absence of This differs greatly from the postoperative course activity using "sl-labelled fibrinogen. Increased of total hip or knee arihroplastic procedures. counts were present after seventy-two hours via \fleight bearing and motion are progressively "5l-1abe11ed fibrinogen and remained localized to encouraged during the early postoperative course the calf in seventeen of the remaining twenty-slx of the above mentioned orthopaedic procedures. patients. Confirmation of location was achieved by Motion activates muscle pump blood return and repeat phlebography. Nine of the forty cases diminishes stasis. Clearance of blood from the showed extension of calf thrombosis into the lower extremity is largely dependent upon and popliteal and/or iliofemoral veins via phlebogra- augmented by contraction of the calf muscles. A phy. Four of the nine cases developed pulmonary patient in a short or long leg cast loses the benefit embolism.6'Philbrick and Becker concluded that an of active ankle joint motion and is at increased risk acute calf DVT is not a benign event, and that for developing a DVT, specifically a calf DVT. propagation of a calf DVT varies from J.6-2307s.e" Deep venous thrombosis occurring in the There is no clear evidence that an isolated, acute soleal or tibial veins has been given little attention calf DVT should be treated with anticoagulation; due to the reported low incidence of fatal PE and however, fo1low-up diagnostic studies to evaluate the reiative infrequency of post-phlebitic syn- for proximal extension should be mandatory. drome. Fatal pulmonary emboli are commonly Recentiy, Baker and Bick recommended treating thought to originate from large thrombi within the distal thrombosis in the same fashion as a proximal iliofemoral venous segment. Moser and LeMoine thrombosis on an acute basis, followed by followed thify-six DVTs to evaluate for subsequent coumadin or for three to six weeks, then pulmonary emboli with respect to location of the for three months.6" DVT. Twenty-one of the thirty-sk thrombotic How to treat an acute calf DVT remains con- events occurred in and were isolated to the calf troversial. From the previous discussion it should veins; whereas, fifteen DVTs were classified as be clear that the prevention of a calf DVT is crucial proximal DVTs. Eight of the fifteen proximal DVTs due to the possibility of proximal extension and demonstrated pulmonary embolism via a ventila- subsequent increased chances of pulmonary tion-perfusion scan. Only one of the eight patients emboli. This is especially important if the patient had clinical symptomatology. None of the calf will have a short or long leg cast with increased DVTs had a positive screening for a pulmonary chances of stasis in the calf venous system. embolism.6" Even though this study down-plays the Another important which cannot be importance of calf thrombosis, indirectly it illus- overemphasized is the history of previous DVT. trates a common theme which can be seen These patients should be treated as high risk, and throughout the literature. Many readers and strong consideration should given towards an researchers automatically conclude that only the aggressive prophylactic approach. In the presence proximal thrombotic event should be treated. of a previous DVT, an accurate history of prior However, the possibility of proximal extension surgery and/or trauma should be evaluated along from a popliteal to include the proximal with any other risk factors. if there is not a reason- iliofemoral complex was not specifically addressed able explanation for the DV! then there should be by Moser and LeMoine. suspicion of other predispositions towards the development of DVT such as hereditary or CHAPTER 54 277 acquired coagulopathies ( III or pro- subendothelial collagen is a nidus for clot formation. tein C or S deficiencies). Baker and Bick also Trauma or surgery in the arca of the venous return suggest taking an extensive family history to look may result in endothelial damage. Excessive manip- for DVT or predisposing coagulopathies,6e ulation of the extremity and prolonged angular positioning (e.g. flexion of the knee) can also pro- PATHOGENESIS duce intimal damage. The most common cause of endothelial pathology during foot and ankle surgery It is clear from the literature that any major surgical would be the use of a thigh tourniquet. Not only can candidate over the age of forty, potentially could the tourniquet cause direct effects on the intima of develop a DVT. However, a brief overwiew of the the vein with prolonged use, but the tourniquet can pathogenesis of venous thrombosis will illustrate also cause damage in an indrrect fashion. Anoxia the same potential for formation in ma1'or surgery of produced by the tourniquet is postulated to effect the foot and ankle. In 1856, Virchow described a the endothelium at cusp sites, where the endothelial triad of pathophysiologic events which herald the cells are either rendered malfunctional or are shed evolution of venous thrombosis.6' The effects of due the decreased oxTgen tension.60,'7 Multiple stud- any surgical procedure on venous blood flow, ies have shown stagnation of blood flow at the cusp endothelial integrity of a vessel, and viscosity or sites in the soleal venous complex. An area with hypercoagulabilty of blood are directly relared to pooled blood and an absence of endothelium is at the development of DVT. high risk for clot formation. Venous stasis is affected by both the type of Some degree of hypercoagulability may be anesthesia and the position of the patient and present in patients who undergo malor orthopaedic extremity during anesthesia. General anesthesia is surgery.5e Fibrinogen has been show to be associated with greater occurrence of DVT than increased following surgery.6o This may be due to spinal anesthesia. This is possibly due to the periph- an increase in the production of fibrinogen, but eral vasodilatory effect from generai anesthetic most likely is secondary to a shutdown of the fibri- agents which results in pooling or stasis of blood in nolytic system.3e,74 This, coupled with the the soleal sinusoids.To-l2 Paralyzing agents used dur- documented decrease of anti- III in post- ing endotracheal intubation also contribute to operative orthopaedic patients,22 produces venous stasis by inactivating the calf pump.60 hypercoagulability.?e Some orthopaedic surgeons Venographic studies have also shown a decreased use supplemental antithrombin iII with heparin as venous return in patients in the supine position.r,ra prophylaxis against DVT.' Excessive and prolonged rotation of the hip has been shown to diminish venous return. Three PROPTTYIAXIS separate studies, utilizing intra-operative veno- graphic techniques, documented a narrowing effect There are two approaches for the prophylaxis of on the femoral vein with excessive internal and venous thromboembolism. The first approach external rotation of the hip for the placement of a would be considered primary prophylaxis and total hip implant.17'75,?6 Although there is not neady entails pharmacologic and mechanical methods as much hip repositioning during major surgery to administered prior to surgery in order to prevent the foot and ankle, a surgeon may elect to maxi- thrombosis formation. The second method utilizes mally internally or externally rotate the lower diagnostic screening tests (e.g. venography) for the extremity at the hip ioint to aid in the Tateral or early detection of deep venous thrombosis, and medial dissection of the rearfoot or ankle. This institution of treatment for the prevention of an probably has a negligibie effect on venous stasis embolism. The second method is called secondary and endothelial damage, but could be contributory prophylaxis. The significant risk of failure in pri- during a long procedure utilizing a tourniquet with mary prophylaxis is the development of a DVT, the patient under general anesthesia and in the while the risk of failure in secondary prophylaxis is supine position. In essence, there is a cumulative embolism. Obviously, an embolism is a much effect by each of these seemingly minor factors. greater concern than a deep venous thrombosis, An intact endothelial surface is essential for the because an embolism carries with it the immediate prevention of thrombous formation.a Exposed risk of death. It is always preferential to prevent a 278 CI]APTER 54 disease process rather than make an eaiy diagno- PHARMACOLOGIC METHODS sis and then treat the pathology. In addition, a DVT which does not produce a clinically significant Heparin embolism is not without potential sequelae (e.g. Heparin is the most widely-used and studied form posrphlebitic syndrome). It is highly recom- prophylaxis surgical and non-surgical mended to use primary prophylaxis whenever of in the patient, and is considered some the benchmark possible to prevent the development and possible by for thrombosis proph|lzxi5.orsost Heparin gly- sequelae of a deep yenous thrombosis.a is a cosaminoglycan porcine A plethora of literature has been published derived from either intestinal mucosa or beef lung. The main utility of concerning prophylaxis against the development of heparin the prophylaxis and treatment DVT deep venous thrombosis. There are no controlled for of studies demonstrating a significant incidence of lies in its ability to inhibit thrombin formation. This is accomplished primarily by inhibiting factor Xa DW with sr-rbsequent pulmonary emboli in unpro- and potentiating effects antithrombin III. phylaxed patients unclergoing foot and ankle the of Clotting factor Xa helps convefi prothrombin to surgery. However, it is quite evident that mafor capabllity specific heparin reconstructive surgery of the foot and ankle should thrombin. The ol a preparation inhibit factor Xa is directly propor- have prophylactic measures for the prevention of to tional to in vivo anticoagulation.6e Heparin selves as venous thrombosis when clinically warranted. The a cofactor and accelerates the formation of a mole- authors recommend that a physician assess the risks cular complex between antithrombin and and benefits of multiple treatment options before III factors (XII, XI, IX, and X). This deciding on a particular regimen. For proper assess- increases inhibition thrombin formation.B' ment, a thorough history and physical is essential. of Thrombin has positive feedback effect on the This will help identify patients who are candidaies a clotting cascade, specifically on factors V and MII. for prophylaxis, as well as those who may be intol- The presence of thrombin can result in the genera- erant of a pafiicular prophylactic modality (e.g. a large quantities more thrombin. Some patient with a low-normal count preopera- tion of of feel that the most impofiant effect of heparin is the tively may not do well with adjusted dose heparin avoidance of this positive feedback mechanism by due to its potential side effect of thrombocltope- the prevention of thrombin formation."'3 nia). It is also highly recommended that a team Thus, in order for heparin to be effective as a approach be usecl in regard to DVT prophylaxis. prophylactic agent, must given prior to This should optimize patient care and minimize it be surgery as it works by inhibiting the formation of risks. The following is a brief synopsis of the most thrombin. Heparin does not dissolve a formed common methods used for DVT prophylaxis. thrombus. Fixed low-dose heparin is usually given According to Raskob and Hull, an ideal agent units two hours preoperatively, followed by for prophylaxis is efficacious, well-tolerated by the 5000 units either every eight or twelve hours. This patient, and accepted by health care providers. The 5000 regimen is commonly referred to as mini-dose prophylactic modality shor-rld also be economical, heparin or fixed low-dose heparin. easily administered, and require minimal monitor- Heparin is clearly an effective prophylactic ing.6' Prophylaxis can either be administered in a agent in moderate risk general surgical and medical mechanical or pharmacologic manner. There are patients. Browse reviewed 24 studies involving multiple forms of medical prophylaxis including 4932 general surgery patients. Heparin given sub- but not limited to unfractionated heparin, low mol- cutaneousiy every B-12 hours following a 2 hotr ecular weight heparin, coumadin, dextran, and preoperative dose was shown reduce the inci- aspirin. Mechanical prophylactic modalities include to dence DVT from 300/o compared to earl1. ambulation, elevation of extremities, gradient of to )(%, patients receive heparin.6" There is a , and intermittent pneumatic who did not debate as whether the twice a day or three times compression devices. to a day dosing schedule is superior. There is no con- trolled study which has unequivocal evidence supporting one over the other. However, Clagett reviewed 29 studies which included over 8000 CHAPTER 54 279 patients. In patients treated with heparin dosed Dihydroergotamine is given at a dose of 0.5mg sub- every 12 hours, there were 289 DVTs out of 2446 cutaneousiy Nvo or three times per day. The effect patients, or 11.8%. Patients who were dosed every of dihydroergotamine may act synergisticaliy with eight hours developed DVTs in 159 cases out of a heparin and improve the prophylactic effect of possible 2039 patients, which equates to a 7.5o/o heparin; however, DHE used alone is not reported incidence. Bleeding and wound were to have a significant effect on the prevention of calf also compared between the two dosing regimen. DVTs.6o With an arithmetical study comparison, Although slightly more bleeding complications Browse showed that a combination of heparin and occurred with the Q B hour dose (20/1742 vs. dihydroergotamine had a 60/o incidence of DVT 36/383D statistically there was not a significant dif- compared to the 70o/o rale with heparin alone. ference. The development of wound hematomas However, this may not be statistically significant was almost identical between the two groups.'] when evaluating the number of patients along with Even thotigh it has been shown that prophy- the percentages.6o Significant vasospastic side effects laxis decreases the incidence of DVTs in have placed the use of DHE in disfavor. It is not rec- orthopaedic surgery,'5 most authorities do not rec- ommended in the presence of coronary afiery ommend low dose heparin for the prophylaxis of disease or peripheral arterial ischaemia. Currently, high risk patients, especially those with total knee the combination is not being marketed in the or hip implants or hip fractures.*868' Mohr's review United States due to the above stated side effects.' of DVT prophylaxis for hip and knee implants at the Mayo Clinic showed that only 9 out of a possi- Heparin with Antithrombin III ble 409 cases were chosen for the use of heparin Heparin has also been combined with supplemen- as a prophylactic measure.'e This reluctance to use tal antithrombin III. Postoperatively, there is a low dose heparin in high risk patients is supported decrease in the plasma concentration of circulating by its ineffectiveness when compared to other reg- antithrombin III. Antithrombin III has imens.o88e Because of this, physicians have used an properties due to its ability to inactivate adjusted dose of heparin for high risk patients."'e0 involved in the coagulation cascade. Francis et al. The heparin is adjusted postoperatively to keep the compared heparin and antithrombin III to dextran partial thromboplastin time within 4 seconds of 40 for prophylaxis against DVT in hip implant high normal. Increased bleeding compiications arthroplasty. Antithrombin III levels were moni- have been noted with this type of heparin dosing, tored postoperatively and found to be much closer but it is an accepted alternative for the prophylaxis to preoperative levels as compared to the dextran of high risk patients, and appears more effective group. Francis hypothesized that this translated into than regular mini-dose heparin. the decreased rate of DVT in the antithrombin III In general, heparin should not be used for eye group. Only 3 of 41 patients in the antithrombin III surgery, , and spinal surgery due to the group were diagnosed with DVT via ascending significant consequences of bleeding. Low dose venography, while 72 of 47 patients in the dextran heparin does not need to be monitored; however, a group were diagnosed with DVT by the same baseline platelet count is recommended and should method." Although the cost of antithrombin III be followed if patients have a low normal count, or may be prohibitive compared to equally if patients will be on extended outpatient use. effective methods, it may prove cost-effective if a Thrombocytopenia is an obseled side effect in up substantial decrease in DVT can be shown. to 70o/o of patients with long term heparin use.e' Additional clinical studies are needed to fr:rther outline the potential benefits of antithrombin III, Heparin with Dihydroergotamine alone or in conjunction with heparin. Low dose heparin with dihydroergotamine (DHE) has been shown to be more effective than plain low Low Molecular Weight Heparin dose heparin for the prophylaxis of high risk During the last few years, 1ow molecular weight patients.e2ea Dihydroergotamine increases the veloc- heparin (LM\f heparin) has become an attractive ity of venoLls return by decreasing the diameter of alternative for DVT prophylaxis. LM\f heparin has a the vessel. Its vasoconstrictive effects are due to similar mechanism of action as standard heparin, alpha adrenergic activity on the smooth muscle cell. 280 CHAPTER 54

but, proportionally, has a greater effect on factor Xa. As the molecular weight of heparin decreases, Table 3 the effect on the activared pafiial thromboplastin time diminishes, but the effect on factor Xa remains METHODS OF COUMADIN significant.6e,e5 This translates into adequate PROPIIYIAXIS FOR DWPE activity with less of a chance of bleeding when dosed properly. LMV heparin is METHOD 1 reported to have greater bioavailability and a longer biological half life.0q,sr,e5 This allows once a day dos- Evening before surgery - 10mg ing. LMW heparin also has decreased effects on Evening of surgery - 5mg when compared to unfractionated heparin, Adjust PT to 15-1Bs and subsequently causes less thromboq,topenia. Several studies have demonstrated the efficacy METHOD 2 of LMV heparin for prophylaxis against DVT.13,e6e8 Begin 72-74 days preoperatively Specifically, LM\7 heparin has been shown to be Maintain PT 1.5-3.0 sec. above control effective in orthopaedic surgery.1{,17,e5o0,oo,10u In a POD #1 Adjust PT ro 15,18s meta-analysis performed by Bergqvist using 32 ran- domized trials, LMIX/ heparin was shown to be METHOD 3 more efficacious than standard low-dose heparin. Evening of surgery 10mg In the LMW heparin group, there were no fatal pul- No Coumadin POD #1 monary emboli out of 5027 patients; whereas, in POD #2 adjust PT ro 16-18s the heparin group, there were 5 fatal pulmonary (Modified from Merli5e) emboli from 4873 patients.ea The optimal time for initial administration has not yet been established. There are a few disadvantages which make Three different regimens currently exist: lO-72 coumadin less attractive than other prophylactic hours preoperatively, 2 hours preoperatively, or modalities. Monitoring must be performed to postoperatively.ea LMW heparin has been primarily ensure appropriate dosing. Even with the INR used outside of the United States for the past fifteen between the recommended levels (.2.0-3.0D, a 5.Oo/o years. Results from ongoing clinical trials should incidence of major bleeding has been repofied.6e increase the availability of this modality, as ir The time before the anticoagulant takes effect is at appears to be an efficacious, cost effective prophy- least 36 hours. The risk of hemorrhage is grearer lactic agent. than with other pharmacologic methods. There are also many drug interactions with comadin which Coumadin may increase the risk complications. Before insti- Oral anticoagulation via coumadin is a first line tuting coumadin prophylaxis, the physician should choice for prophylaxis in high risk orrhopaedic review the particular patient's to look patients 2,1,60,61 Coumadin also has been shown to be for possible interactions with the coumadin. effective in gynecologic'u' and general surgery Often, oral anticoagulation is continued until patients.r02 Coumadin works by its inhibition of vit- the patient is fully ambuiatory. Post-discharge amin K dependent coagulation factors II, \TI, IX, X, coumadin administration has been advocated to , and . There are many accepted Iast between 4. and 12 weeks.'o Paiement et al. ways to institute coumadin therapy, but almost all reviewed 258 patients who were treated with start with a dose given sometime preoperatively. adjusted low-dose coumadin for the prevention of The three most common ways to institute venous thromboembolism. Patients were given 10 coumadin prophylaxis are listed inTable 3. milligrams of coumadin the night before surgery, and adjusted coumadin postoperatively to maintain a PT between 14 and 16 seconds. The patients con- tinued prophylaxis for 72 weeks postoperarively. There were no fatal pulmonary emboli and only two non-fatal pulmonary emboli, both of which occurred prior to discharge. A11 ten major bleeding CHAPTER 54 281 episodes occurred during hospitalization. Sixteen Mechanical prophylaxis is opted for when patients experienced minor bleeding episodes, there is a contraindication for heparin and/or none of which required treatment.lo coumadin in the face of a potential bleeding com- plication. There is definite evidence that IPC boots MECTIANICAL MODALITIES have a significant reduction in the formation of dis- tal DVT; however, there is some concern with Mechanical modalities for DVT prophylaxis includes proximal DVT.84 107 Francis et al. found a proximal leg elevation, earTy ambulation, gradient compres- DVT rate of l2o/o with the use of IPC boots, com- sion stockings, and intermittent pneumatic pared to a 3o/o occurrence rate with coumadin compression devices. Early ambulation and postop- prophylaxis rn major orthopaedic procedures. The erative leg elevation clearly have been shown to be authors concluded that coumadin was significantly effective in the prevention of DVT.,03 However, these more effective than IPC for the prophylaxis of DVT methods should not be relied upon solely in the in hip replacement patients. The high incidence of presence of moderate to high risk patients.l,63 proximal DVT with IPC only, caused termination of Gradient compression stockings (GCS) aid in venous the study.'?1 In contrast, Hull and associates have feturn and may prevent trauma to the vessel.'oa GCS shown that full-iength IPC boots lowered the inci- has a compressive effect which commonly stafis at dence of iliofemoral DVT.'o' l8mmHg at the ankle and tapers to 8mmHg at the IPC boots are especially useful in patients popliteal fossa. There is 1OmmHg of pressure at the who cannot tolerate pharmacologic prophylaxis low thigh, which decreases to BmmHg at the due to potential bleeding complications (e.g neu- midthigh.63 Jeffery and Nicholaides report that GCS rosurgical patient).10e Intermittent pneumatic reduce the rate of DVT by 60Vo when compared to compression can be used solely or in conjunction control groups. This effect is increased to 850/o when with pharmacologic agents, and has been used in an additional modality is implemented. The same many triais wiih exceilent success. The devices are authors recommend GCS as a first line modality in applied prior to surgery and are mechanically all hospitalized patient with low dsk.'oa GCS are used inflated intermittently throughout the surgery. This for moderate and high risk patients, but the addition is continued after the surgery until the patient is of another mechanical or a pharmacologic method ambulatory. The only downside is that the devices is mandatory.o:,u'' may be cumbersome for the patients. The most common, effective form of mechan- icai prophylaxis is intermittent pneumatic leg DISCUSSION compression, which will help prevent thrombosis in two ways. First, the compression device will Any patient who is scheduled to undergo recon- increase blood return from the lower extremity and strl-rctive surgery of the foot and/or ankle and is help prevent stasis. However, in lower leg surgery over forq. years of age should be evaluated for the operative extremity does not benefit from this additional risks factors for the development of deep and may still be predisposed to venous stasis and yenous thrombosis. By most, foot surgery or podi- subsequent DVT. The second effect of the com- atric surgery is considered minor surgery. However, pression device is that it will increase the activity of by using criteria from other specialties it is quite evi- the fibrinoll,tic system. Increased levels of prosta- dent that a sector of podiatric surgery is indeed cyclin and fibinolytic byproducts have been major surgery. For instance, a patient who is sched- demonstrated with the use of IPC boots.105 106 This is uled to undergo a major rearfoot, ankle, or pantalar a systemic effect of the compression, and is not afihrodesis will most likely experience general dependent on where the device is placed; thus, the anesthesia in a supine position with the utilization operative extremity still will receive some benefit of a thigh tourniquet. Most of these procedures take from the increased . The effect on the greater than fwo hours to complete successfully. A,11 fibrnolytic system is directly proportional to the of these factors have been shown to increase the surface area of tissue compressed; therefore, thigh- predilection for a patient to develop a DVT, espe- high IPC boots are recommended. Graded cially in the presence of additional known risk sequential IPC boots are preferred over uniform factors, such as obesity, cigarette , estrogen IPC boots. Optimally, the IPC boots are placed on supplementation, , and immob llization. the non-operative extremity prior to surgery. 282 CHAPTER 54

Additionally, a majority of these patients will normalized ratio and represents a standardized or be non-weight bearing in a leg cast for at least six corrected . The authors attempt to to eight weeks. The literature suggests that immo- keep the INR at about 2 or the PT between \3 and blhzation is no longer a risk factor once ambulation 15 seconds. Other surgeons have recommended the begins. However, it may be prudent to view use of postoperative coumadin prophylaxis ranging patients who are non-weight bearing in a cast as from one milligram'ue to 5 milligrams per day.'0 having a gteater risk for the development of DVT, Lotke et al. recently gave strong recommendation although the patients are ambulatory on the con- for the continued prophylaxis of patients on an out- tralateral extremiry with crutches or a walker. patient basis for up to 3 months.T The authors routinely evaluate major surgical Currently, the authors continue the 2.5 mil- cases with respect to thrombotic risk factors. ligram per day dose on an outpatient basis for the Patients who have an additional risk factor for entire non-weight bearing time period. For the first developing a DVT are considered at moderate risk. 4 weeks a repeat INR is obtained on a weekly basis Moderate risk patients carry a 70-40o/o chance of and is communicated to the attending surgeon and calf DVT, a 2-700/o chance of a proximal DVT, and the co-admitting physician. Any adiustments can be 0.7-0.7o/o chance of a pulmonary embolism.5er'e made from this value. Coumadin is a highly protein These patients are given heparin 5000 units subcu- bound drug which may interact with other drugs taneously two hours preoperatively, followed by that a patient may be taking. Some medications 5000 units every eight hours. In addition, the cause altered activity of coumadin due to protein authors usually employ a mechanical method for displacement (e.g. NSAIDs). Patients must be prophylaxis as well. instructed to be aware of signs of bleeding. A potential drawback to the administration of Other simple measures can be performed to preoperative heparin is the fear of hemorrhage and help decrease risk factors for the development of subsequent postoperative wound complications DVT. A Jones compressive dressing which encom- due to uncontrolled bleeding. There is no signifi- passes the gastroc-soleal complex may help to cant literature to support the contention that low increase venous retLlrn. Elevation of the affected dose heparin causes bleeding. The authors have extremity with eady range of motion of found that meticulous dissection, intra-operative the contralateral limb can also be beneficial. hemostasis, and judicious use of drains have a Although there is no specific documentation, iso- much greater effect on bleeding and wound heal- metric exercises for the operative extremity while ing than the use of preoperative heparin. casted may improve venous blood return. Early Gradient compressive stockings or pneumatic mobilization of the patient postoperatively is essen- compression devices are added preoperatively. tial to decrease of the formation of thrombosis. Gradient compressive stockings are used in moder- ate risk patients while pneumatic compressive REFERENCES devices are utilized in the high risk patients. Care must be taken in obese patients when applying 1. Silver D: An oveniew of venor,ts thromboembolism prophylaxis, gradient compression stockings, as the proximal Am J Surg 767:537. 1997. 2. Kllmar R, McKinney \fP, Raj G: Perioperative prophylaxis in aspect may not have a large enough diameter to venous thromboembolism, AmJ Mecl Sci 306:336, 1993. encompass the entire thigh. The compression 3. \flilde AH, D Ambrosia RD, Hartman.]T, Raskob GE, \noolson ST: effect Symposium: Clinical management of thromboen'rbolic clisease in stocking may actually produce a tourniquet tlre lower extremities, ContemP Otthop 77:77, 7988. in this instance. ,1. Glaor IL{ and Bartholomew JR: Deep venous thrombosis. In (eds) the realization that patients have a signif- Young JR, Graor RA., Olin J\fl Bartholomen'JR Pe4pberal \fith Vascular Disease St, Louis, Mosby Year Book, 1991. icant risk of forming a DVT after discharge from the !. Swayze OS, Nasser S, Roberson JR: Deep venous thrombosis in hospital, moderate and high risk patients are con- total hip arthroplasty Ortbop Clin Not'th Am 23:359, 1992. 6. Huisman MV, tsuller HR, ten Cate J\(/, van Royen EA, Vreeken J, sidered for outpatient thrombotic prophylaxis. Kersten MJ, Bakx R: Unexpected high prevalence of silent pul- Patients who do not have a contraindication to monary embolisnr inpatients v'.ith deep venous thrombosis. Cbest 91: 198-502, 1989. coumadin are placed on 2.5 milligrams of coumadin 7. Lotke PA, Steinberg ME, Ecker ML: Significance of deep venous on postoperative day number one. Sequential INR thrombosis in the lower extremity aiter total joint arthroplasty, Clin Ortbop 299:25. 1994. vaiues are obtained and compared to the preopera- tive value. An INR stands for the international CHAPTER 5,i 283

8 Lotke PA, Ecker ML: Low-molecular-weight heparin vs 28. Mohr DN, Silverstein MD, Murtaugh PA, Harrison JM: for prophylaxis against deep-vein thrombosis (letter), N Engl J Prophylactic agents for venolrs thrombosis in elective hip lled 330:863, 1993. surgery, Arcb Intern Med 1,53:2221,, 7993. Levine M. Hirsch J, Gent M, et al.: Prevention of deep vein throm- 29 Nlohr DN, Silverstein MD, Ilstrup DM, Heit JA, Morey BF: bosis after elective hip surgery: A randomized trial comparing Venous thromboembolism associatecl with hip and knee afil'ro- lou. molecular weight heparin with standard unfractionated plastyr cuffent prophylactic practices and outcomes, Mayo Clin heparin, Ann Inten't Med. 11,1:545, 1997. Proc 57:861., 1.992. 10 Paiement GD, \flessinger SJ, Hughes R, Harris \7H; Roudne usc l0 O Brien BJ, Anderson DR, Goeree R: Cost-effectiveness of enoxa- of adjusted low-dose warfarin to prevent venous thromboem- parin versus wafarin prophylaxis against deep-vein thrombosis bolisn-r after total hip replacement, /.Bone Joint SLtrg 7 5 :893, 1993. after total hip replacement, Cdn Med Assoc-[ 750:1083, 7994. \Wessinger 11. Paiement GD, Beisaw N. Lotke PA, Elia EA, S.J, Harris Hess Laffer Fridrich R, K, -WH: 31 Oertli D, P, Durig M, U, Jaeger Advances in the prevention of thromboembolic disease afier Kaufmann R, Harcler F: Prevention of in hip and knee surgery, Ofihop Reu 78 (Suppl):i, 1989. patients with hip fractures: low molecular weight heparin versus 12 Leyvraz PF, Richard J, Bachmann F, et a1: Adjusted versus fixed dextran, WbrldJ Surg 76:980, 7992. close subcutaneous heparin the prevention of DVT after total hip )2. Swiestra BA, Stibbe J, Schouten HJ: Prevention of thrombosis replacement, N EnglJ Mecl 309:951, 1983. after hip arthroplasty. A prospective stucly of preoperative oral 13 Leytrraz PF, F, Bachmann BohnetJ, Breyer HG, Estoppey D, Haas , Actd Ortbop Scancl 59:139, 7988. S, Hochreiter Mair Sorensen al: '$(roolson J, Jakubek H, J, R, et 33 ST, Watt Intermittent pneumatic compression to Thromboembolic prophylaxis JM: in total hip replacemeflt: a compar- prevent proximal deep venous thrombosis during and afier total ison between the 1ow molecular weight Lomoparon hip replacement. A prospective, randomized study of compres- and heparin-dihydloergotamine, BrJ Surg 7992. 19:917, sion alone, compression and aspirin, and compression and t4 Leyvraz PF, Bachmann F, Hoek Buller HR, Postel M, Samama J, low-dose waffarrn,.l Bcu'te Surg 73(A):501 1991. M, Vandenbroek MD: Prer.ention of deep vein thromlrosis after Joint , Amstutz HC, Friscia DA, Dorey F, Carney BT: 'Warfarin prophy- hip replacement: rafldomised compadson between unfraction- 34 laxis to prevent moftality from pulmonary embolism after total ated heparin and low molecular weight heparin, Br Med .[ hip replacement, Bone Surg 77(A):327, 7989. 303:543, 7997. J Joint Trou'bridge A, Boese CK, s(oodruff B, Brindley HH Sr, Lowry 15 Stringer M, Steadman C, Hedges A, et al: Deep vein thrombosis It \X,E. Spiro TE: Incidence of post hospitalization proximal deep after elective knee surgery: An incidence study of J12 patients, venous thrombosis after total hip arthroplasry. A pllot stucly, Clin J Bone Joint Surg 7l-B:192, 1989. Ofibop 299:203, 1994. 16 Stulberg B, Insall William G, et al: Deep vein thrombosis fbl- J, pro- lowing total knee replacement: An analysis of srx hundred and 36 Oster G, Tuden R, Colditz G: A cost effective analysis of phylaxis against deep vein thrombosis in malor ofihopedic thirtlr-eight afilroplasties, / Bone Joint Surg 66(A):194, 7984. 7987 11 Planes A, Vochelle N, Fagola M: Total hip replacement and cleep surElery, JAtr[-4 257:203, vein thrombosis: A venographic and necropsy study,./ BoneJoittt 31 LiebermanJ, Huo M, Hann'ayJ, Salvati E, Sculco T, Sharrock N: Surg 72(8):9, 7990. The prevalence of deep venous thrombosis afier total hip arthro- 18 Planes A, Vochelle N, Mazas F, et al: Prevention of postoperative plastl with hypcrtensive epidural anesthesia, J Bone ./oint Surg venous thrombosis: A ranclomized trial comparing unfractionatecl 76(A):341, 1994. \Wadenvik heparin srith low molecular weight heparin in patients undergo- 38. Erikkson BI, Kalebo P, Anthymyr BA, H, Tagenborn L, ing total hip replacement, Tltromb Haentosr 60:,107, 1988. Risberg B: Prevention of deep-vein thrombosis and pulmonary i9 Haas S, Insall J, Scuderi G, et al: Pneumatic sequential compres- embolism after total hip replacement. Comparison of low-molec- sion boots compared with aspirin prophylaxis of dcep vcin ular-weight heparin and unfractionated heparin, J Bone Joint thrombosis after total knee arthroplasqr. J Bone Joint Surg SLUE 73(Nt481, 1991. 72(A):27.1990. 39. Eriksson B, Eriksson E, Erika G, et al: Thrombosis after hip 2l) Feldman DS, Zuckerman JD, Malters I, Sakales SR: Clinical effi- replacement: Relationship to the fibrinolyic system, Acta Ofihop cacy of aspirin and dextran for thromboprophylaxis in geriatric Scancl 60:759. L989. patietlts, J Ot"tbop Tr.tumd 7:1, 7993. 40 Taberner D, Poller L, Thompson J, et al: A randomized trial of a 21 Francis CY/, Pellegrini VD Jr, Marder VJ, Totterman S, Harris CM. low molecular weight heparin (enoxaparin) to prevent deep vein Gabriel KR, Azodo NIV, Leihe( KMr Comparison of warfarin and thrombosis in patients undergoing elective hip surgery, N Engl J external pneumatic compression in prevention of venolls throm- Med. 375:925. L986, bosis after total hip rcplacement, J,A-LLA 267 2971 . 7992. 11 Powers P, Bent M, Jay R, et al: A ranclomized trial of less intense 22 Francis CW, Pellegrini \D Jr, Marder VJ, Haris CM, Totterman S, postoperative warfarin or aspirin therapy in the prevention of Gabriel KR, Azodo MV, Baughman DJ, Roemer S. Burke J, venous thromboembolism after surgery for fractured hip, Arch Goodman TL, et al: Pre\.ention of venous thrombosis after total Intern Med 7191771,. 1,989. hip arthroplasty. Antithron'rbin III and low-dose heparin com- 42 Hill SL, Berry RE, Ruiz AJ: Deep venous thrombosis in the trauma pared with dextran 40, J BoneJoint Surg 71(A):321 , 1,989. patient, Am Surg 60:405, 1991. 23 Gerhan TN, Yett HS, Robetson LK, Lee N4-{, Smith M, Salzman 43 Olin.f!il, Graor R,A.. O Hara P, Young JRr The incidence of cleep E\i[: Low-molecular-weight heparinoicl compared r,-ith wadarin venous thrombosis in patients undergoing abclominal aortic for prophylaxis of deep-vein tlrrombosis in patients nho are anelrrysm resection, / Vasc Surg 18:1037, 1993. operated on for fracture of the hip. A prospective, randomized 44 Holt DB, Swegle JR: Deep venous thrombosis in the surglical tti^l,.J Bone Joint Surg 73(4):194, 1991. intensive care unit. Sttrg Clin Nottb Am 71:811, 1991. 24 Hodge WA: Prevention deep vein thrombosis after total knee of 15. Rutherford SE, Phelan JP: Deep venous thrombosis and pul- arthroplasty, Clin Ot"tbop 271:101, 1997. monary embolism in , Obstet Gynecol Clin Nofib Am 25 Hull R, Raskob G. Pineo G, Rosenblum D, Evans \il, Mallory T, 78:345, 7997. Anquist K, Smith F, Hughes G, Green D, et al: comparison A of 16. Marshall Prophylaris of deep venous thrombosis and pul- subcutaneous low-molecular-weight J: heparin with warf'arin monary enrholi,m. CanJ Surg J4:

t0 Mannucci PM, Citterio LE, Panajotopoulos N: Low-dose heparin 79 Gitel S, Salvanti E, $0essler S, et a1: The effect oftotal hip replace and deep-vein thrombosis after total hip replacement, Tlcromb ment and general surgery on antithrombotin IiI in relation to Haemost 36:757. 7976. venous thrombosis. J Bone.Joit'rt Surg 67-A:653, 1979. 51 Sikorski JM, Hampson \VG, Staddon GE: The natural history of 8t) Fareed.J: Venous thromboprophylaxis in the 1990s: A perspec- etiology of deep vein thrombosis after total hip replacement. / live, Semin Tbomb Hemctst 77:377, 7997. BoneJoint Surg(Br) 63,U7 177, L987. 81. Fareed.l, Hoppensteadt D, Walenga JM, Bick RL: Current trends 52 Kakkar W. Fok PJ, Muffay \x,'J, Paes T, Merenstein D, Dodds R, in the devlopment of anticoaElulant and antithrombotic drugs. Farrell R. Crellin RQ, Thomas EM, Morley TR, Price AJ: Heparin Merl Clin Nofih Am,78: 773-731, 1994. and clihydroergotamine prophylaxis against thrombo-embolism 82 Stein B, Fuster V: Pharmacology of anticoagulants and platelet after hip arthroplasty, J BoneJoint Sury 67-81538, i985. inhibitor drugs. In Schlantz RC, Alexander Rnf (eds) Hursts 7he 53 Johnson R, Green JR, Charnley J: Pulmonary embolism and its Hean. 8th ed., Neu'York, McGraw Hill, 1994. prophylaxis following the Charnley totai hip replacement, Clin 83 Bell WR, Bllazarian SD: Coagulation, coagulation disorders, and Ofthop 727:72J, 7977, antithrombotic therapy. In Young JR, Graor RA, Olin JSr, 54 Fredin HO, Nillius AS: Fatal pulmonary embolism after total hip Bartlrolomew JR (eds): PeriPberal Vascular Disease St. Louis, replacement, Acta Ofibop Scand 53:407, 1982. Mosby Year Book, 1991. 51 McGlamry ED, Banks AS, Downey MS: Cctmprebensiue Textbook 84 Clagett G, Reisch J: Prevention of venous thromboembolism in of Foot Surgery. 2nd ed., Baltimore, \X/illiams and \X/ilkins, 1992. general surgical p:rtients: Results of meta-analysis, Ann Surg 5h Jahss MH: Disorders of the Foot dnd Ankle: Medical and Surgical 208:227,7988. Mdn.tgement. 2nd ed., Philadelphia, 1991. 8i Collins R, Scron-rogeour A, Yusuf S, et al: Reduction in fatal pul- 51 Mann R A., Coughlin MJ: Surgery af tbe Foot and Ankle. 6th ed., St, monary embolism and venous thrombosis by perioperative Louis, Mosby, 1993. administration of subcutaneous heparin: Overuiew of results of 58 Gould JS: Operatiue Foctt Surgeryt. Philadelphia, $(r'.B. Saunders randon'lzed trials in general, orthopedic, and urologic surgery, l/ Company, 1!!,1. EnglJMed 318: 1162, 1988. 59 Merli GJ: Update, Deep vein thrombosis and pulmonary 86. Salzman EW: Surgical mana6lement of venous thromboembolism. embolism prophylaxis in orthopedic sur6lery, Med Clin Nortb Ant In Colman R\V. Hirsch J, Marder VJ. Salzman E1W (eds): 77.lc)7 I OOt Heruostdsis and Thrombctsis. Philadelphia, J.B Lipincott 60 Browse NL, Burnand ICA, Thomas ML (eds.): Deep venous Companv, 1987. thrombosis: prevention. In Diseases qf tbe Veins. Lonclon Eds,'ard 87 Prevention of venous thrombosis and pulmonary embolism: con- Arnold, 1988. sensLrs conferen ce. JLMA 256: 7 14-7 49, 1986. 61 Raskob GE, Hull RD: Prevention of Venous Thrombosis. In 88 Morris GK, Henry APJ: Prevention of deep-vein thrombosis by Kwaan HC,Samama MM 9eds'): Clinical Thrombosis. Boca Raton, lou-close heparin in patients undergoing total hip replacement. CRC Press. 1989. Lancet 2: 797, 1974. 62 ClaEaett GP, Salzman E$(r: Prevention of r.enous thromboem u9 Venous Thrombosis Clinical Study Group. Small doses of subcu- bolism in snrgical patlents. N Eng.l Med 290:93-95, 1911. taneous sodium heparin in the prevention of deep vein 63 Goldhaber S, Morpurgo M: fbr the \(/HO/ISFC task Force on thrombosis after elective hip operations. BrJ Surpi,62: 348, 7975. Pulmoonary Embolism: Diagnosis, treatment, ancl prevention of 90 Taberner DA. Poller L, Thomson JM, Lemon G, rX/eighill FJ: pulnronary embolism, JAMA 2681727, L992. Randomized study of adjusted versus flxed 1ow dose heparin 64 Consensus Conference. Prevention of venous thrombosis and prophylaxis of deep vein thrombosis in hip surgery. Am J Surg pulmunary cmboli.m. JAW4 );61- r r. 1q86. 76: L)33-935,7989. () ). Hull RD, Raskob GE, Hirsch J: Prophyiaris of venous throm- 91. Loscalzo J, Schafer AI: Anticoagulants, antiplatelet agents, and boembolism: An overwie*', Cbest 85:3f9, 1985. Fibrinol)tics. In Loscalzo J, Creager MA, Dzau VJ (eds): Vascular 66 Moser KM, LeMoine JR: Is embolic risk conditioned by location Mediciner: A textbook of vascular biology and diseases. New of deep venous thrombosis. Ann Intern Med,94: 439-414, 1981. York, Little, Boston, Bro.w-n and Company, 1989. 67 Kakkar \rV, Howe CT, Flanc C, Clarke MB: Natural l'ristory of 92. Gent Mand Robens RS: A meta-analysis of the studies of dihy- postoperative deep vein thrombosis. Iancet, II: 230-232, 1969. droergotamine plus heparin in the prophylaxis of deep-vein 68 Phillrrick JT, Becker DM: Calf deep venous thrombosis: A wolf in thrombosis. Chest 89:3965 4005. 1986. sheep's clothing. Arch Intern Mecl, 748: 2731-21,38, 1988. 93. linblacl B: Prophylaxis of postoperative thomboembolism with 69 Baker 'WI, Bick RL: Deep vein thrombosis: Diagnosis and low dose heparin alone or in combination with dihydroergota- Mana€iement. Med Clin Nortb Am78: 685-772, 7c)94. mine. A revrew. Acta Cbir Scand Suppl543:31-42, 1988. 70 Lindstrom B, Ahiman H. Jonsson O, et al: Blood flon, in the 94 Bercqvist D: Current tlends in the manag;ement of postsurgical calves during surElery, Acta Cbir Scand 713:335, 7977. thromboembolism: The role of low molecular r.eight heparin, 71 Linclstrom B, Ahlman H, Jonsson O, Stenqvist O; Influence of Sem in Thomb Hemost 17:332, 1991. anacsthesia on blood flou, to the calves during surgery. ,4cla 95. 'Woif H: Low-molecular-weight heparin. Med Clin Nofib Am Anaestb Scand, 28: 201-203, L986. 78:133-713. 1994. 72 Clark C, Cotton L: Rlood flow in deep r.eins of the legs: 96. Turpie AG: EfHcacy of a postoperative regimen of enoxaparin in Recording technique and evaluirtion of method to increase flow deep vein thrombosis prophylaxis. AmJ Surg 767:532, 7991. during operation, Br.l Sttrg 55:277, 7958. 97 Leizorxicz A, Haugh MC, Chapuis FR, Samama MM, Boissel JP: 73 Nicolaides A, Kakkar V, Renney J: Soleal sinuses and stasis, Br./ Low molecular weight heparin in prer.ention of perioperative sttrg 567 3rJ7 , 7970. thrombosis, Br Med J 30i:913, 1992. 74 Nicolaides A, Kakkar V, Field E, et al: Venous stasis and deep 98. Spiro TE, Johnson GJ, Christie MJ, L1,6115 RNI, MacFarlane DE, vein thrombosis, BrJ Surg 59:713, 1972. Blasier RB, Tremaine MD: Efficacy and safety of enoxaparin to 75 Stamatakis J. Kakkar V, Sagar S, et al: Femoral vein thrombosis prevent deep venous thrombosis after hip replacement surgery. and total hip replacement, Br Med J 11:223, 1977 . Enoxaparin Clinical Trial Group. Ann Intem Med 121,:81,, 7994. 76. Johnson R, CannichaelJHE. Almond HGA, Loynes RP: Deep vein L)L) Spiro TE, Colwell C\W, Trowbridge,A,,A. (for the enoxaparin clinical thrombosis following Charnley arthroplasty, Clin Ortbctp trial group): A clinical trial comparing the efficacy and safety of 732:24, 1978. enoxaparin, a low molecular weight heparin and unfractionated 77 Hamer JD, X{alone PC. Silver LA.: The po2 in venous valve pock- heparin for the prevention of deep l'enous thrombosis after elec- ets: its possible bearing on thrombogenesis . BrJ Surg 6&166, 7987. tive hip replacement surgery (Abstract) Blood 8O(snppl) 167, 7992. 78 Kluft C, Verheijen J, Jie A, et al: The postoperative fibrinolltic 100 Breyer HG: Tl'romboprophylaxis with heparin and low molecu- shutdou,n: A rapidly revefiing acute phase pattern for the fast lar weight heparin in elective hip surgery: Curent status and acting inhibitor of tissue type plasminogen acti\.ator after trauma, perspectives, Semin Tbomb Hemost 7l:336, 1991. rcond J Llin Lab lttt est rs:605. lo8<. CHAPTER 54 285

101. Taberner DA, Poller L. Burslem RV. Jones JB: Oral anticoagulants D Angelo A, Kluft C. Verheijen J, et al: Fibrinolltic shutdos,-n alier controllecl by the British comparative thromboplastin versus 1ow- surgely: Impairment of the balance betlveen tissue-type plas- dose heparin in prophylaxis of deep vein thrombosis. Br MedJ minogen activator and its specific inhibitor, Eur J Clin Inuest 7:272, 7978. 15:308. 1985. 102. Clagett GP, Salzman Er Prevention o fvenous thromboembolism. Fields $0S: and . Is there a place for low molecular Prog Cardiouasc Dis 17:345, 1975. weight heparins. Semin Thomb Hemost 17:311,, 1,991,. 103. Meilman E: Leg elevation in prophylaxis of thomboembolisl'r Francis C$(r, RicottaIJ, Evarts CM, Marder VJr Long-term clinical obser- (letter). Lancet 313:248, 1994. vations and venous functional abnornalities after asymptomatic 104. Jeffery PC, Nicolaides AN: Graduatecl compression stockings in venous thrombosis follorving total hip or knee afihroplasty, C/1,? the prevention of postoperative deep vein thrombosis. BrJ Surg ofihop 232277, 1988. 77:380'383. 1990. Goldhaber SZ, Savage DD, Garrison RJ, Castelli SlO, Kannel \VB, 105. Salzman E\Xr McNamana GP, Shapiro AH, Robertson LK, NlcNamara PM. Gherardi G. Feinleib M: Risk factors fbr pulmonary Donovan AS, Blume H!(/, Sweeny J, Kamn RD, Johnson MC, embolism: The Framingham study, AmJMecl 74:7023.7983. Block PM: Effect of optimization of hemodynamics of fibrinolltic Green D: Prevention of thromboembolism after , activity and antithrombotic efTicacy of external pneumatic calf Semin Tbomb Hemctst 77:317, 7997. compresqion. Ann SurB 206:636-641. lox-. Harris S(rH, Salzman EW. Athansoulis C, Waltman AC. Baum S, 106. Guyton DP, Khayat A, Schreiber H: Pneumatic eornprcssion DeSanctis RW: Comparison of warfarin, low-molecular-weight stockings ancl prostaglanclin slthesis - a pathway of fibrinolysis? dertran, aspirin, and subcutaneous heparin in prevention of Crit Care Med L3: 266. 1.985. venous thromboembolism follolr,'ing total hip replacemenl. J Bone 107. Caprini JA, Arcelus JI, Traverso CI, Hasty JH: Low molecuiar .[oint Sur.q., 56A,1 1.552-1562, 1974. neight heparins and external pneumatic compression as options Halt D, Binkert B: An overwiew of noninvasive methods of deep vein for venous thromboembolism prophylaxis: A surgeon s perspec- thron'rbosis detection. Clin Imag 11:179, 1990. tive, Semin Thomb Hemost 17;356. 1.991. Hirsch J, Hull R: Natural history and clinical features of venous throm- 108. Hull RD, Raskob GE, Gent M, Mcloughlin D, Julian D, Smith FC, bosis. In Hemostdsis and Thrctmboszs. Colman R1fir, Hirsch J, Dale I, Reed-Davies R, Lofthor,rse RN, Anderson C: Effectiveness Marder VJ, and Salzman ErW (eds,), Philadelphia, J.B Lipincott of intermittent pneumatic leg compression for preventing deep Company, 1P87. vein thrombosis after total hip replacement,J.lMl263:231.3, 1990. Hirsch J, Levine N1: Prevention of venous thrombosis in patients under- 109. Skillman lJ, Collins RIC, Coe NP, Goldstein BS, Shapiro R.\1, going major ol'thopaedic surgical procedures, Br J Clin Pract Zeruas NT, Bettman l4-A., Salzman E-W: Prevention of cleep 5-r/r?p Suppl 6i:2. IoEo vein thrombosis in neurosurgical patients: A controlled, random- Hirsch I, Salzman E\W: Prevention of venous thromboembolism. In ized trial of erternal pneumatic compression boots. &z4qery, Hemostasis and Thrombosis. Colman RW, Hirsch J, Marcler VJ, and 83:354-358. Salzman E\(r (eds.), Philadelphia, J.B Lipincott Company, 1987. 110. Pollen L: Optimal therapeutic range for oral anticoagul^t1o11. Rec Hull RD, HirschJ, Sackett DL, Taylor DV, Carter C, Turpie AG, Powers Adu Blctctrl Coagul j:21j, 1,))7. P, Gent M: Clinical validity of a negative venogran in patients with clinically suspected venous thrombosis. Circulation 61,622, 798L. Hull RD. Delmore J, Hirsch J, et al: Effectiveness of intermittent pul satile elastic stockings for the prevention of calf and thigh vein ADDITIONAL REFERENCES thrombosis in patients undergoing elective knee surgery, Tbrombosis Researcb L6:37, 1979. RH, Hirsch Diagnosis of Deep-Vein Arcelus JI Caprini JA, Traverso CI: International Perspective on Venous Hull RD, Secker-$falker J: Thromboembolisn'r Prophylaxis in Surgery, Semin Thromb Thrombosis. In Colman R\V, Hirsch J, Nlarder VJ. Salzman E\[ Hemost 77:322. 1997. (eds): Hemostasis and Thrombosisr Basic Principles and Clinical Agnelli G, Cosmi B, Ranucci V, Ranga C, Nlosca S, Lupattelli L, Di Practice, ed 2. Philadelphia, Jts Lippincott, 1987. Filiplpo P, Rinonapoli E, Nenci GG: Impedance plethysmography Kwaan HC, Samama MM. Lecompte T: Pathogenesis of Thrombosis. In (eds.), in the diagnosis of asymptomatic deep vein thrombosis in hip Clinical Thrombosis. Kwaan HC ancl Samama MM Boca sur€aery. A venography-controlled study, Arch Intern Med Raton. CRC Press. 1989. 757:2767,7997. Lagerstedt CI, Olsson CG. and Fagl'rer BO: Need for long-term lntico- aglllant treatment in symptomatic calf-vein thrombosis. Lancet. 2: Alpet.lS and Dalen JE: Pulmonary Embolism. In Hlrrst s The Heart. Schlantz RC and Alexander R\V (eds.), Sth ed., Neu,' York, 515-518,1985. McGrar. Hill, Inc., 1994. Landefielcl CS, Chren MM, M1,q15 A, Geller R, Robbins S, and Goldman and a Barnes R$(l'. Nix ML, Barnes L, Lavender RC, Golden \ffE, Harmon BH, L: Diagnostic yield of the autopsy in a university hospital Ferris EJ, Nelson CL: Perioperative as)-mptornatic venous throm- community hospital. N Eng.l Med 3L8: 7219-1254, 7988. bosis: Role of duplex scanning versus venography, J Vasc Surg Leonarcl EF: RheolopSr of thrombosis. In Hemostasis and Thrombosis. E]ilr (eds.), 9:251. 7989. Colman RW, Hirsch J, Nlarder VJ, and Salzman Browse NL Burnand IlA, Thomas ML (eds.) In Diseases of the Veins. Philadelphia, .J.B Lipincott Company, 19ti7. Lonclon, Eclward Arnold. 1988. Deep venous Thrombosis: Mal1ory TH. Vaughn BK, Lombardi AV Jr, Mitcl'rell MB: Impedance Pathology, Chapter 16. plethysmography for surueillance of deep venous thrombosis fol- Bounameaux H, Huber O, Khabiri E, Schneider PA, Didier D, Rohner lowing early clischarge of total hip replacement patients, A: Unexpectedly high rate of phlebographic deep venous throm- Otbopedics 73:7317, 7990. bosis fbllon'ing elective general among Murphy TP. Cronan lJ: Evolution of cleep vein tlrrombosis: x prospec- patients given prophylaxis with low-molecular-weight heparin, tive evaluation with US, Ractriologt 177:113, 1990. Arch Surg 728:326, 7993. Raskob GE Hull RD: Venous Thrombosis. In Clinical Tbrombosis. CapriniJA, Natonson RA: Postoperative deep vein thrombosis: Current Kwaan HC ancl Samarla MNI (eds.), Boca Raton, CRC Press, 1989. lWH: clinical considerations. .tenx in Thornb Hemost 15:241, 7989. Salzman E$fl, Harris Prevention of venous thromboembolism in Carter C, Gent M: The epidemiology of venous thrombosis. In ofthopaedis patients, J Bone.loint Surg 58-A:903, 1976. Coleman R, Hirsch J, Marder V, et al (eds): Hemostasis and Seyfer A, Seaber A. Dombrose F. Urbaniak J: Coagulation chang4es rn elective sr,rrplery ancl trallma, Ann. Surg., 193:210, 1981. Thrombosis: Basic Principles of Clinical Plactice, Philaclelphia. .fB Lippincott, 1987. Thomas DP: Pathogenesis of venous thrombosis. In Hemoslasis and Colditz GA, Tuclen RT. and Oster G: Rates of venous thrombosis after Tbrombosis. Colman RW. Hirsch J, &Iarcler VJ, and Salzman E\7 general surgery, combinecl results of randomised clinical trials. (eds.). Philadelphia, J,B Lipincott Company, 1987. 'Wolf and Lancet, II: 113-146, 1.986. H, Encke A, Haas S, $flelzel D: Comparison of the efficacy safety Sandoz low molecular r'.eight l'reparin and unfiaction- Comerota AJ, Katz X,lL, \X/hite JV: $fhy cloes prophylaxis $,'ith external of pneumatic compression for deep vein thrombosis farl?, Am.l Surg ated heparin: Interim analysis of a multi-center ltial, Selnin Thomb 164t26i. L992. Hem()st 17:343. 1997.