Interactions between coagulation and inflammation.

The coagulation system evolved as a mechanism to limit the loss of vital elements from the internal milieu following mechanical injury to the circulatory system. The innate immune system developed as a rapid response system to detect and clear microbial invaders that have breached the integument of multicellular organisms. The coagulation and innate immunity systems coevolved from a common ancestral substrate early in eukaryotic development, and these 2 systems retain a highly integrated and coregulated circuitry of signals and control elements that defend the host following tissue injury and microbial invasion. Advances in the understanding of the molecular mechanisms that control clotting and inflammation have led to the successful development of recombinant human activated protein C for the treatment of human septic shock. Optimal use of this and other anticoagulant agents in sepsis will necessitate further basic research into the critical linkage between coagulation and innate immunity.