Postgrad Med J: first published as 10.1136/pgmj.45.526.539 on 1 August 1969. Downloaded from Postgrad. med. J. (August 1969) 45, 539-542. Coagulation disturbances in shock H. G. LASCH Justus Liebig University, Giessen, Germany Summary (1) Inhibitors like anti-thrombokinase, heparin and Hypocirculation causes hypercoagulability with an progressive anti-thrombin, partly released by mast increase of Factors V and VIII, and a diminished cells, partly by the vessel endothelium, which platelet count. In shock hypercoagulability is interrupt momentarily excessive activation pro- followed by hypocoagulability due to loss of cesses. Factors I, II, V, VIII and XIII together with (2) Fibrinolysis which links cellular (leukocyto- thrombocytopaenia and qualitative alterations in kinase) and plasma factors (anti-thrombin III- platelet properties. This reversal is caused by dis- anti-plasmin activity) to haemostasis in the peri- seminated intravascular coagulation consuming pheral circulation, and reacts in the same manner clotting factors and platelets-consumptive coagulo- as the system of clotting factors. pathy. Under normal conditions, the activation of blood Fibrin deposits occur in the peripheral vasculature coagulation is automatically followed by the activa- of the viscera and are associated with a rising oxygen tion of fibrinolysis. debt, and, in clinical situations, with haemorrhagic (3) Cellular phagocytosis of the reticulo-endothelial diathesis, visceral necrosis and irreversible shock. system (RES) plays a decisive role in controlling Localization of the microthrombi is under the in- latent coagulation. It has been shown that the copyright. fluence of catecholamines, ACTH and aldosterone. liver and spleen clear activated breakdown sub- Administration of heparin in clinical shock may stances of haemostasis from the circulating blood. prevent the development of consumptive coagulo- The concentration of Factor VII and Factor IX pathy, but is without effect if disseminated intra- was found to be higher in the portal vein than in vascular coagulation is already present. the hepatic veins (Lasch, Mechelke & Nusser, Anti-fibrinolytic therapy is contraindicated where- 1957). as streptokinase-induced fibrinolysis has experimental Spaet et al. (1961) have demonstrated that the and clinical justifications. injection of thromboplastin into the portal vein of rats, that is ahead of the RES, has no bearing on the http://pmj.bmj.com/ VESSEL wall and haemostasis are closely interrelated. global activity of haemostasis, whereas the injection Experimental and clinical investigations suggest that of the same amount of thromboplastin into the a continuous physiological turnover of clotting hepatic vein results in defibrination. By electron- factors and platelets is necessary for the proper microscopy, Lee & McCluskey (1962) have demon- functioning of the vessel wall. Intermediary products strated material in the Kupffer cells ofthe liver which of intravascular haemostasis such as fibrin monomer resembles fibrin monomer. and damaged platelets influence permeability, Activation of the coagulation system in the peri- rigidity and resistance of the capillaries. It may very phery and clearance of the intermediary coagulation on October 6, 2021 by guest. Protected well be possible that insoluble and soluble collagen products thus not only guarantee the latent turnover stemming from the vessel wall form the connection in the system of haemostasis, but also maintain the between tissue structure and the blood flowing by eucoagulability of the blood. In this way the circula- the vessel wall. tion itself becomes a decisive factor, since it com- The central idea of 'latent coagulation' is the con- bines and balances activation, turnover, breakdown tinuous breakdown of prothrombin to its subunits, and production of the factors of haemostasis. prothrombin, auto-prothrombin C, thrombin, Fac- Slowed-down circulation and stagnation of the blood tor IX and Factor VII, which again determine the in larger vessels ofthe blood stream (hypocirculation) global activity of haemostasis in blood. The steady result in hypercoagulability. The tendency to de- turnover of clotting factors and platelets results in velop thrombosis in patients with cardiac insuffi- the actual activity of haemostasis. Under normal ciency, post-surgery and post-delivery, can thus be conditions control mechanisms prevent a manifest explained. clotting of the blood in the circulation. These are: Alterations in the system of haemostasis are also Postgrad Med J: first published as 10.1136/pgmj.45.526.539 on 1 August 1969. Downloaded from 540 H. G. Lasch observed in different types of shock. Our experi- with consecutive consumption coagulopathy is made ments in dogs, cats and rabbits have shown that in the laboratory. hypercoagulability can be found in the initial stage Fibrin thrombi in the peripheral circulation are of haemorrhagic shock, bums, and fat embolism and the morphologic substrate of a consumption co- most pronouncedly in endotoxin shock. In this stage agulopathy. The extent of fibrin deposition is de- the clotting analysis shows an increased activation pendent on the intensity of the intravascular clotting of Factor V and Factor VIII and an initial decrease process, the insufficiency of control mechanisms and in platelets. on special localizing factors. Muller-Berghaus & In the later stages of shock the clotting time be- McKay (1967) have shown that intravascular co- comes prolonged. At this point fibrinogen, pro- agulation with consecutive fibrin deposition in the thrombin, Factor V, FactorVIII andespeciallyFactor renal glomerular capillaries is decreased by pre- XIII are decreased, and at the same time a decrease in treatment of the animals with oc-adrenergic blocking platelets is observed. The maximal amplitude in the agents such as dibenzamine or dibenzyline. Mar- thrombelastogram becomes small; r- and k-values garetten and co-workers (1965) have supplied an- often become extremely prolonged. Defects in other example for the importance of localization platelet function become obvious: adhesion and factors: thrombin infusions only result in fibrin agglutination of the platelets are decreased. Analysis deposition and adrenal haemorrhages if ACTH is of their partial function reveals loss in ATP, sero- administered together with the thrombin infusion. tonin, platelet factor 3 and glycogen. Loss of the McKay & Muller-Berghaus (1968) have demon- platelets in ATP and decrease of the maximal ampli- strated that an activation of Hageman factor by tude in the thrombelastogram can directly be corre- ellagic acid with simultaneous inhibition of fibrino- lated. lysis by s-aminocaproic acid only results in fibrin In summary, it can be said that a stage is reached deposition if noradrenaline is administered at the in the system of haemostasis which corresponds to same time. that after clotting of blood in vitro. Factors and In the same manner morphologic equivalents can platelets are consumed intravascularly by increased be shown in patients who have died from shock with turnover. To define this pathogenetic mechanism in consumption coagulopathy. Clinical and laboratorycopyright. terms of its dynamics we have introduced the term data may possibly correspond to the morphologic 'Verbrauchskoagulopathie' (consumption coagulo- substrate if the autopsy is performed immediately pathy). after death and post mortem lysis is prevented. The quantitative differences in the reaction of Sandritter & Lasch (1967) were able to demonstrate haemostasis are dependent on shock and its starting fibrin depositions in various organs in about 70% mechanism. The most pronounced changes are seen of patients who had died in shock. following endotoxin, fat embolism, bums and hae- The consequences of consumption coagulopathy morrhagic shock, in this order. Endotoxin itself may which manifest themselves in acute circulatory accelerate the turnover of clotting factors and failure are (Table 1): http://pmj.bmj.com/ platelets. Moreover, catecholamines released by the (1) A haemorrhagic diathesis which is not obliga- action of endotoxin may effect an increased tendency tory and which is caused by the breakdown of ofthe platelets to agglutinate and a loss in platelets in haemostasis. Suggilation and petechiae are ob- the circulation. In in vitro experiments the addition served. Secondary fibrinolysis can enhance the of catecholamines to platelet-rich plasma results in haemorrhagic diathesis by generation of fibrinogen a pronounced decrease in platelets. Stimulation of and fibrin split products. Split products may inter- the adrenergic system results in the release of free fere with the structure of a haemostatic plug. In fatty acids into the blood which activate Hageman addition to this, split products inhibit the aggrega- on October 6, 2021 by guest. Protected factor. Crowell & Smith (1964) attribute an im- tion ofplatelets. Laboratory analysis should differen- mediate activation of haemostasis to the shifting of tiate between bleeding caused by consumption the pH to acidosis. Lipids and intravascular inter- coagulopathy and bleeding caused by hyperfibrino- mediary products of the coagulation, moreover, load lysis. the RES. If one considers that stasis of the blood in (2) Disturbances in the blood flow of various large areas of impaired microcirculation is followed organs with secondary damage: renal cortical necro- by a slower flow of blood to the RES, the accumula- sis and acute renal failure, adrenal haemorrhage and tion