Prevention by glucocorticoids of disseminated intravascular coagulation induced by endotoxin: mechanisms.
The therapeutic efficiency of two glucocorticoids (hydrocortisone and dexamethasone) on endotoxin-induced intravascular coagulation was investigated in the rat. Coagulation and platelet aggregation studies were performed and plaminogen was assayed. Our results indicate that pretreatment of the animals with large doses of these steroids within a few hours prior to endotoxin totally prevents the consumption in Hageman factor, measurable contact product activity, platelets, fibrinogen, plasminogen, and the loss in platelet aggregability and serotonin. In addition to this, the hypercoagulable state  consecutive to endotoxin, characterized here by shortenings in the partial thromboplastin and recalcification times and by an increase in the availability of platelet procoagulant activity, was also totally prevented by the steroid pretreatment. On the other hand, it is shown that these glucocorticoids do not interfere in the normal rat with platelet aggregation (tested with thrombin,adenosine diphosphate, and collagen), but with the availability of platelet procoagulant activity. This last phenomenon, in addition to that of an interference in vivo with the mechanism of activation of Hageman factor, are believed to be responsible for prevention by glucocorticoids of endotoxin-induced disseminated intravascular coagulation.
D000818:Animals; D001772:Blood Cell Count; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D003907:Dexamethasone / Q000627:therapeutic use*; D004211:Disseminated Intravascular Coagulation / Q000517:prevention & control*; D004731:Endotoxins / Q000494:pharmacology; D004926:Escherichia coli; D005174:Factor XII / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D006854:Hydrocortisone / Q000627:therapeutic use*; D010714:Phosphatidylethanolamines / Q000097:blood; D010958:Plasminogen / Q000032:analysis; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D012701:Serotonin / Q000097:blood; D013997:Time Factors
D004731:Endotoxins; D010714:Phosphatidylethanolamines; D012701:Serotonin; D003907:Dexamethasone; D005174:Factor XII; D005340:Fibrinogen; D010958:Plasminogen; D006854:Hydrocortisone