Inhibiteurs de la coagulation et états infectieux graves

A pathologic activation of the coagulation system occurs during severe infections and is a major determinant of subsequent organ dysfunction. The natural anticoagulants (Tissue factor pathway inhibitor [TFPI], Antithrombin, and Protein C) serve as potent inhibitors of thrombin generation. They are consumed or inhibited during severe sepsis justifying a therapeutic supplementation. Three large randomized controlled studies were performed with these inhibitors. No effect on mortality could be documented with recombinant TFPI or AT concentrates but a biological interaction with heparin therapy could have biased the results. Treatment with recombinant activated PC was associated with a significant reduction in the mortality rate of severely ill patients but additional studies showed a lack of effect in less severe patients and in children. Two trials are underway to definitely document the reduction of mortality in patients with septic shock. From these different studies, three major applications can be drawn: (1) the early changes in the plasma levels of these inhibitors are strongly predictive of subsequent mortality and organ failure and may be used as prognostic indexes; (2) the specific effects of these inhibitors on the intravascular coagulation process have not been prospectively studied and it remains to be documented if the therapeutic control of haemostasis could decrease by itself the mortality rate; (3) numerous experimental and clinical studies have shown that these inhibitors serve as potent regulators of inflammatory and microcirculatory changes, that could be used in new and specific therapeutic applications.