Pathogenesis and treatment of disseminated intravascular coagulation in the septic patient.
The incidence of sepsis and complications stemming from septicemia has remained constant in recent years despite improved levels of monitoring and care. Disseminated intravascular coagulation (DIC), a syndrome that occurs frequently in septic patients, is associated with increased mortality. Organ dysfunction is also a common sequela that is strongly correlated with DIC. Cytokines released early in the course of sepsis stimulate a procoagulant state that causes development of intravascular fibrin deposition. In a later stage of DIC, bleeding may occur in parallel because of consumption of clotting factors and inhibitors. Therapeutic strategies to attenuate or reverse these conditions have focused on multiple stages of the molecular cascade of events, including preventing cytokine induction, inhibiting coagulation processes, and promoting fibrinolysis. Recent clinical trials have supported the use of antithrombin and activated protein C supplementation in DIC associated with severe sepsis. Studies of other novel therapeutic avenues are still ongoing. Future efforts may be directed at combining 2 or more agents to achieve prompt and successful reversal of DIC.
Levi
M
M
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
D000991:Antithrombins / Q000627:therapeutic use; D001777:Blood Coagulation; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000097:blood; D004211:Disseminated Intravascular Coagulation / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D005342:Fibrinolysis; D006801:Humans; D008074:Lipoproteins / Q000627:therapeutic use; D011486:Protein C / Q000627:therapeutic use; D018805:Sepsis / Q000150:complications*
D000991:Antithrombins; D016207:Cytokines; D008074:Lipoproteins; D011486:Protein C; C051928:lipoprotein-associated coagulation inhibitor