Activation of Intravascular Coagulation by Endotoxin: the Significance of Granulocytes and Platelets

Abstract

The importance of granulocytes and/or platelets in endotoxin-induced generalized intravascular coagulation was studied as well as thrombocytopenic rabbits. Neutropenia and thrombocytopenia were induced by oral administration of busulphan. Generalized intravascular coagulation, as indicated by renal glomerular microclot formation, was initiated by two intravenous injections of endotoxin. Granulocyte counts before the second injection of endotoxin were most significantly related to activation of intravascular coagulation whereas platelet counts either before the first or second injection of endotoxin were not definitely related to the activation process. Renal glomerular microclots occurred in rabbits after two injections of endotoxin even when the platelet counts were between 500 and 5000/mul. These experiments indicated that granulocytes but not platelets are essential to the activation of endotoxin-induced intravascular coagulation.

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

“…These enzymes activate several clotting factors [34]. The leukocytes may therefore contribute to the induction of intravascular coagulation as is supported by recent stud ies [28], Endotoxin adheres to the surface of erythrocytes in vitro [29] and in vivo [36]. This interaction, which is thought to be a mechanism for detoxification of endotoxin, results in hemolysis [29].…”

Enhanced generation of monocyte tissue factor and increased plasma prothrombin fragment1+2 levels in patients with polycythemia vera: Mechanism of activation of blood coagulation

“…There is substantial evidence suggesting that monocyte TF plays a prominent role in activation of the coagulation system and clot formation: (1) Increased TF levels were demonstrated in monocytes from patients with a high incidence of thromboembolic complications such as bacterial sepsis with disseminated intra-vascular coagulation (DIC) [10,11], cancer [26], inflammatory bowel disease [27], pregnancy-related complications, and other [10,11]. The patients with the highest monocyte TF levels had the greatest incidence of thromboembolic phenomena [28]; (2) Fibrin had been identified on the surface of endotoxin-activated monocytes [29]; (3) Increased TF activity was found in monocytes and macrophages adjacent to areas of fibrin deposits in tissues of patients with inflammatory and immunological disorders [10,11]; (4) Animals rendered leukopenic failed to develop DIC in response to endotoxin injections and fibrin could not be detected in their renal glumeruli [30].…”

Neutrophil adherence induced by lipopolysaccharide in vitro. Role of plasma component interaction with lipopolysaccharide.

“…Studies of the mechanisms by which bacterial endotoxins produce such severe reactions suggest that the biologically active lipopolysaccharide (LPS) portion ofendotoxin interacts with a variety of humoral and cellular mediators (6). The neutrophil may play an important role in endotoxin-related syndromes (4,5,7), but the mechanisms by which LPS enhances the injurious potential of neutrophils remains uncertain. The adherence ofneutrophils to vascular endothelium is a critical prelude to neutrophil-mediated injury (8), and neutrophil sequestration in vascular beds in response to minute quantities of LPS has been recognized for decades (9).…”

“…Endotoxemia has been linked to a variety of catastrophic disorders, including acute lung injury ( 1,2), renal failure (3), disseminated intravascular coagulation (4), and circulatory collapse (5). Studies of the mechanisms by which bacterial endotoxins produce such severe reactions suggest that the biologically active lipopolysaccharide (LPS) portion ofendotoxin interacts with a variety of humoral and cellular mediators (6).…”