This Reactome module describes the multi-step process of fibrin formation, which is initiated by the thrombin (FIIa)-catalyzed conversion of fibrinogen molecules to fibrin monomers (Ni F et al., 1989; Pechik I et al., 2006; Riedel T et al., 2011). Fibrin monomers rapidly and spontaneously associate into large multimers, which in turn elongate into protofibrils that later aggregate to form fibers, creating a three-dimensional network. This structural organization is essential for the mechanical properties of the clot (reviewed by Doolittle 1984; Litvinov RI & Weisel JW 2017; Feller T et al., 2022). The fibrin network is further stabilized by Ca2+ -dependent cross-linking of fibers, which is mediated by the thrombin-activated factor XIII (FXIIIa). Adhesion of integrin ?IIb?3, a platelet surface receptor, to the fibrin network contributes to platelet aggregation and stabilizes the forming clot (Litvinov RI et al., 2016; Höök P et al., 2017). The process of fibrin clot formation has been reviewed in detail (Medved L & Weisel JW 2009; Weisel JW & Litvinov RI 2017; Pieters M& Wolberg AS 2019; Butera D & Hogg PJ 2020; Murano G 2024).
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