Antithrombin III in animal models of sepsis and organ failure

Antithrombin III (AT III) is the physiological inhibitor of thrombin and ot her serine proteases of the clotting cascade. In the development of sepsis, septic shock and organ failure, the plasma levels of AT III decrease consi derably, suggesting the concept of a substitution therapy with the inhibito r. A decrease of AT III plasma levels might also be associated with other p athological disorders like trauma, burns, pancreatitis or preclampsia. Acti vation of coagulation and consumption of AT III is the consequence of a gen eralized inflammation called SIRS (systemic inflammatory response syndrome) . The clotting cascade is also frequently activated after organ transplanta tion, especially if organs are grafted between different species (xenotrans plantation) During the past years AT III has been investigated in numerous corresponding disease models in different animal species which will be revi ewed here. The bulk of evidence suggests, that AT III substitution reduces morbidity and mortality in the diseased animals. While gaining more experie nce with AT III, the concept of substitution therapy to maximal baseline pl asma levels (100%) appears to become insufficient. Evidence from clinical a nd preclinical studies now suggests to adjust the AT III plasma levels to a bout 200%, i.e., doubling the normal value, During the last few years sever al authors proposed that AT III might not only be an anti-thrombotic agent, but to have in addition an anti-inflammatory effect.