Endotoxin‐Induced Intravascular Coagulation and Shock in Dogs: The Role of Factor VII

Abstract

Summary. Endotoxin (E. coli 0111; 2.5 mg/kg) was given via an aortic cannula to groups of normal and factor‐VII deficient dogs to determine whether factor‐VII deficiency afforded protection against endotoxin‐induced shock and intravascular coagulation. Normal dogs showed the dramatic fall in blood pressure characteristic of endotoxin shock and became deeply unconscious throughout the 5 hr period of the experiment. The factor‐VII deficient dogs had a niarkedly less dramatic response. The fall in blood pressure was significant but only transitory and the dogs required additional anaesthesia. Endotoxin‐induced intravascular coagulation occurred in both normal and factor‐VII deficient dogs. However, the decrease in factor‐V activity was greater, and the platelets returned to normal levels more slowly, in normal dogs than in factor‐VII deficient dogs. Plasminogen levels fell significantly in normal dogs, but not in the factor‐VII deficient animals. Autopsies revealed marked differences between the groups. Fibrin‐containing thrombi were regularly observed in normal dogs, but in factor‐VII deficient dogs such lesions were absent or minimal. Hereditary factor‐VII deficiency may therefore afford protection against endotoxin‐induced shock and intravascular coagulation. The difference in intravascular coagulation may explain the modified shock response in factor‐VII deficient dogs or vice versa, but convincing evidence for a causal relationship has not yet been collected.

Effects of Slow Intravenous Administration of Endotoxin on Blood Cells and Coagulation in Dogs

“…coagulation factors. The presence of DIC in this ail ment is in accordance with several studies previously carried out on can ine ES using a bolus injection of endotoxin [14,18], and in agreement with the diagnostic criteria of DIC outlined by Colman et al [7]. The rapid and marked decrease of circulating platelets and leukocytes and the slower consumption of coagulation factors could indicate a direct interac tion of endotoxin with cellular elements of blood, whereas the coagulation process is to a greater extent an indirect process influenced by these inter actions.…”

“…Exposure to the basal membrane due to endothelial damage is thought to result in acti vation of the Hageman factor [7], Furthermore, damage to these cells leads to the release of thromboplastin from the tissues which activate the extrinsic pathway of coagulation. The importance of this activation path way on the coagulation changes in canine ES is emphasized by previous studies done by others where hereditary factor VII deficiency seemed to afford some protection against endotoxin induced intravascular coagula tion [14]. Our study clearly demonstrates that both the extrinsic and in trinsic pathways of coagulation are activated in canine ES.…”

“…This phenomenon is thought to be mediated by at least three mechanisms: (1) activation of the intrinsic pathway of coagulation through Hageman factor, either directly [26] or indirectly through the induction of endothelial damage [7]; (2) re lease of clot-promoting components from cellular elements of blood [12,30,34], and (3) release of tissue substances which initiate thrombin for mation through the extrinsic pathway of coagulation [14]. Although the implication of these mechanisms has been extensively studied, their signif icance is still not fully understood.…”

Factor VII and Ischaemic Heart Disease: Epidemiological Evidence

“…The implications of the epidemiologi cal data on factor VII need to be considered together with evidence of other types -theo retical [Esnouf and Macfarlane, 1968], exper imental [Garner and Evensen, 1974;Zur andNemerson, 1980\ Broze andMajerus, 1980] and from clinical trials [Mitchell, 1981], which, though they are not discussed in detail here, in fact form part of the epidemiological evidence. Thus, the early anticoagulant trials [International Anticoagulant Review Group, 1970] in the secondary prevention of IHD and the more recent Dutch Sixty Plus trial [1980] between them strongly suggest that oral anticoagulants have beneficial effects which are, presumably, partly mediated through their actions on factor VII.…”

The effect of heparinized blood exchange transfusion on endotoxin induced disseminated intravascular coagulation (DIC)

“…•i* the extrinsic pathway of the coagulation System [7,19,23,25]. As a result of the increased thrombin action on fibrinogen, fibrin monomer and crosslinked fibrin is formed in the circulation [13].…”