Modulators of coagulation. A critical appraisal of their role in sepsis.
Widespread intravascular coagulation is common in patients with sepsis. Coagulation abnormalities may result from exposure to endotoxin, from tumor necrosis factor alpha or interleukin 1 release, or from the actions of a more specific mediator, such as vascular permeability factor. The result is marked activation of the contact and coagulation systems; simultaneously, there is decreased fibrinolysis and depressed levels of the inhibitors of the contact and coagulation systems. Multiple agents are being studied to correct these abnormalities. Antithrombin III holds promise because it inhibits a number of factors important in contact and coagulation activation, not just thrombin. Plasminogen activators may prove helpful in increasing fibrinolysis during sepsis; because they have been associated with rebound thrombin generation, however, plasminogen activators may be most effective if used in conjunction with hirudin or a synthetic hirudin analogue. Bradykinin may offset hypotension in sepsis. Protein C may inhibit thrombin formation and also complex with plasminogen activator inhibitor 1, thereby promoting fibrinolysis. Other agents that may prove effective include alpha 1-antitrypsin Pittsburgh, C1-esterase inhibitor, monoclonal antibodies to contact factors, soybean trypsin inhibitors, thrombomodulin, prostaglandin I2, and aprotinin. There are no data to support the use of heparin or fibronectin, except in limited circumstances.
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Department of Internal Medicine, Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill 60612.
D000818:Animals; D001424:Bacterial Infections / Q000150:complications* / Q000503:physiopathology; D001777:Blood Coagulation / Q000502:physiology; D001778:Blood Coagulation Disorders / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D003260:Contact Inhibition / Q000502:physiology; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000503:physiopathology; D006801:Humans; D012016:Reference Values