A) Pro-coagulant mechanisms. TF: a critical initiator of coagulation. Formation of a complex with Factor VIIa (FVIIa) leads to activation of FIX and FX. FXa in the presence of phosphatidyl serine and Ca2+ (prothrombinase complex) amplifies the coagulation cascade through conversion of prothrombin to thrombin, resulting in platelet aggregation, fibrin formation, and inflammation. Thrombin also activates FXI to XIa, which activates FIX to FIXa. FIXa in the presence of phosphatidyl serine and Ca2+ converts FX to FXa, consolidating the coagulation cascade. pRBC, parasitized red blood cells. B) Anticoagulant mechanism. TF pathway inhibitor (TFPI) binds to FXa and inhibits FVIIa/TF complex. Protein C is activated by thrombin (in the presence of thrombomodulin and EPCR), and APC inhibits the coagulation cascade through cleavage of cofactors FVa and FVIIIa. Antithrombin in the presence of heparin sulphate specifically interacts with and inhibits FXa and thrombin. Heparin cofactor II (in the presence of dermatan sulphate) inhibits thrombin. C). Pro- and anti-fibrinolytic mechanism. PAI-1, plasminogen activator inhibitor-1. The zymogen plasminogen is converted to the active serine protease, plasmin, primarily through the action of two-chain tissue plasminogen activator (tc-tPA) or two-chain urokinase (tc-uPA). Both tPA and uPA can be inhibited by plasminogen activator inhibitor-1 (PAI), while plasmin is inhibited by its major inhibitor, α -antiplasmin, and to a lesser extent by α2-macroglobulin (not shown).