Fig. 3.

Cross talk between the coagulation and complement system. The coagulation cascade, the complement system, and fibrinolysis (simplified) communicate through many direct and bidirectional interactions (indicated). Activated clotting Factor XII can activate the classical complement pathway through cleavage of the complement component C1. Similarly, thrombin, kallikrein, and plasmin directly cleave complement component C3, as well as its activation fragments (not shown). Moreover, thrombin can cleave C5 into C5a, which occurs independently of C3 and therefore represents a bypass of the three traditional complement activation pathways (the classical, the lectin, and alternative pathways) [3]. Thrombin-activatable fibrinolysis inhibitor (TAFI) inactivates C3a and C5a in a negative feedback loop. The complement system also amplifies coagulation through the C5a-mediated induction of expression of tissue factor (TF) and plasminogen activator inhibitor 1 by leukocytes (not shown), the latter of which inhibits fibrinolysis. In addition, mannan-binding lectin serine protease 2 (MASP2) of the lectin complement activation pathway triggers coagulation by converting prothrombin to thrombin. MAC, membrane attack complex (C5b–C9); see also [3, 161]