Figure 6.

Pathogenesis of thrombotic and fibrinolytic phenotypes of DIC. DIC with a thrombotic phenotype is induced by the exposure of pathogens/PAMPs, cell debris/DAMPs, and NETs to circulating blood, leading to systemic inflammation and endothelial injury. These events promote activation of coagulation and depression of anticoagulant and fibrinolytic activities, leading to uncontrolled thrombin generation and microvascular thrombosis. When fibrinogen and other clotting factors are consumed; bleeding is a frequent outcome. Microvascular thrombosis and bleeding can be equally damaging to the tissues and organs, frequently contributing to death. DIC with fibrinolytic phenotype occurs more frequently in trauma and APL. In these cases, excessive fibrinolysis due to massive release of t-PA and plasmin generation can destroy the early hemostatic clots releasing fibrin fragment D-dimer. In APL, cell surface annexin II binds t-PA and protects its action from inhibitors, thus enhancing plasmin generation and fibrin degradation. Proteases, such as neutrophil elastase and cathepsins, released by leukocytes during inflammation and trauma, degrade fibrinogen and fibrin, leading to the formation of fibrinogen degradation products that further increase bleeding risk and contribute to organ failure and death. TAFI, thrombin activatable fibrinolysis inhibitor.