Regulation of clotting cascade

Regulation of clotting cascade The coagulation pathway is tightly regulated by numerous mechanisms to maintain hemostatic balance and ensure effective clot formation. Dysregulation of any component can lead to bleeding or thrombotic disorders. This Reactome module describes key endogenous regulators of the clotting pathway, including:Tissue factor pathway inhibitor (TFPI): Forms a quaternary complex with FXa, FVIIa and TF, effectively inactivating FXa and FVIIa to restrict coagulation during the initiation phase (Broze GJ et al., 1990; Maroney SA et al., 2013).Protein C: Activated by the thrombin–thrombomodulin complex on intact endothelial cells. Together with its cofactor, protein S, it inhibits FVa and FVIIIa activities, contributing to anticoagulation (Stavenuiter F et al., 2013).Serine endopeptidase inhibitors, including SERPINC1 (antithrombin III), SERPINA5, SERPINA10 and SERPIND1: Inactivate serine proteases such as thrombin and FXa by irreversibly binding to their serine activation sites (Mushunje A et al., 2003; Boulaftali Y et al., 2010; Huang X et al., 2010).A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13): A metalloprotease, that regulates thrombus formation by cleaving VWF multimers on the platelet surface or in the circulation in the presence of factor VIII (Cao W et al., 2008; DeYoung V et al., 2022; This Reactome module also highlights selected drugs that target clotting factors or their regulators to promote effective clot formation (Petersen LC 2012; Nutescu EA et al., 2016).