The nexus between systemic inflammation and disordered coagulation in sepsis

Abstract

The innate immune system is designed as an early defense system that recognizes and clears potential microbial invaders. The coagulation system co-evolved with the innate immune system from a common ancestral cellular origin, and these two systems continue to exhibit a remarkable degree of integration in their signaling pathways and regulatory circuits following tissue injury and microbial invasion. Inflammatory mediators generate procoagulant signals and intravascular thrombosis activates multiple components of the innate immune system. The success of recombinant human activated protein C for the treatment of human septic shock is likely attributable to its combined effects as an endogenous anticoagulant and an anti-inflammatory molecule. Further advances in the management of severe infections may accrue with a better understanding of the integral link between coagulation and innate immunity.