Coagulation pathway

This Reactome module describes the cell-based model of the coagulation pathway (reviewed by Hoffman M & Monroe DM 2001; Hoffman M 2003; Smith SA 2009; O'Donnell JS et al., 2019). This model describes the intricate interactions between various coagulation factors that, under normal physiologic conditions, occur on membrane surfaces of activated cells at the site of vessel injury. The cell-based model consists of several overlapping stages (reviewed by Hoffman M & Monroe DM 2001; Hoffman M 2003; Roberts HR et al., 2006; Smith SA 2009; O'Donnell JS et al., 2019):Initiation phase, which proceeds through the formation of the activated tissue factor (TF): factor VIIa (FVIIa) complex and TF:FVIIa-mediated generation of a small amount of thrombin (FII) on the membrane surfaces of TF-bearing cells (e.g., fibroblasts, pericytes) (reviewed by Grover SP & Mackman N 2018).Amplification phase, which is mediated by the small amount of thrombin produced in the TF-mediated initiation phase (reviewed by O'Donnell JS et al., 2019). On the platelet surface, thrombin activates factor XI (FXI), factor VIII (FVIII) and factor V (FV). The activated FXI (FXIa) converts factor IX (FIX) to FIXa, which binds the co-factor FVIIIa. The FIXa:FVIIIa complex (the tenase complex) generates activated factor X (FXa) (activated FX) which in turn binds FVa to form the FXa:FVa (prothrombinase) complex. The FXa:FVa complex converts prothrombin (FII) to thrombin (FIIa), which activates more FXI, FVIII and FV creating a positive feedback cycle. Additionally, interactions of FIIa with platelet surface receptors such as surface protease-activated receptors (PARs) contribute to the platelet's activation and degranulation, and the recruitment of additional platelets to the site of injury, where activated platelets aggregate to form the platelet plug (Swieringa F et al., 2018; Sang Y et al., 2021). Activated procoagulant platelets also release clotting factors and expose phosphatidylserine (PS) on their cell membranes providing a surface for the assembly of the tenase and prothrombinase complexes (Swieringa F et al., 2018; Sang Y et al., 2021).Propagation phase, which occurs on the activated platelet surface, generates large amounts of thrombin via FXa:FVa-catalyzed cleavage of prothrombin.In the final phase of clotting, thrombin produced through amplification and propagation stages converts soluble fibrinogen into fibrin, which polymerizes to form insoluble fibrin fibers that are crosslinked by thrombin-activated factor XIII (FXIIIa) to stabilize the platelet plug.

Summary from Reactome (R-HSA-9769740), read 2026-09-23.