Complement and Coagulation: Cross Talk Through Time

Two complex protein defense systems-complement and coagulation-are based on amplifying enzyme cascades triggered by specific local stimuli. Excess systemic activation of either system is pathologic and is normally prevented by a family of regulatory proteins. The 2 systems are ancient biological processes which share a common origin that predates vertebrate evolution. Recent research has uncovered multiple opportunities for cross talk between complement and coagulation including proteins traditionally viewed as coagulation factors that activate and regulate complement, and proteins traditionally seen as part of the complement system that participate in coagulation. Ten examples of cross talk between the 2 systems are described. The mutual engagement of both systems is increasingly recognized to occur in human diseases. Three conditions-paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and the antiphospholipid syndrome-provide examples of the importance of interactions between complement and coagulation in human biology. A better understanding of the mutual engagement of these 2 ancient defense systems is expected to result in improved diagnostics and new treatments for systemic diseases.