Too much of a good thing at the site of tissue injury: the instructive example of the complement system predisposing to thrombotic microangiopathy.

The interplay between the complement and coagulation systems is just beginning to be explored and characterized. This interaction, however, is ancient. For example, if endotoxin is added to the hemolymph of the horseshoe crab, a protease is activated that triggers both the coagulation and complement systems. However, in extant mammals, these 2 cascades have diverged. These infamous "terrible C's" are the scourge of many a medical student (and possibly even a few hematologists). They also are intimately involved in the pathophysiology of thrombomicroangiopathies (TMAs). The complement system generates a procoagulant microenvironment and the coagulation system forms a clot in the renal microvasculature, and thus the 2 systems are partners in mediating multiple pathophysiological conditions.