Figure 4.

Interactions of complement with coagulation and microvasculature in DIC. Pathogens, PAMPs, NETs, cell debris, and DAMPs can activate the complement cascade via 3 pathways, classic (CP), lectin (LP), or alternative (AP), all of which converge at C3. Formation of the C3 convertase of classic and lectin pathways involves cleavage of C4 with formation of C4b convertase component and C4a, an anaphylatoxin that can increase endothelial permeability by signaling through PAR-1 and -4. C3 convertases generated through the 3 pathways, cleave C3 to C3a and C3b. C3a anaphylatoxin activates platelets and leukocytes. C3b is a potent opsonin that contributes to opsonophagocytosis of pathogens, cell debris, and circulating erythrocytes and platelets contributing to extravascular hemolysis and thrombocytopenia. C3b is also a component of C5 convertase, which cleaves C5 into C5a and C5b. C5a anaphylatoxin is a potent chemoattractant and activator of leukocytes and an inducer of TF on monocytes and PAI-1 on endothelial cells (not shown). C5b initiates the formation of C5b-9 terminal complement complex (also known as a membrane attack complex), which makes cytolytic pores in cell membranes, inducing bacteriolysis or cell death in host organs. C5b-9 can activate platelets and induce monocyte TF expression and microparticle release. MASP, mannose-associated serine protease; MBL, mannose binding lectin.