Reactome: A Curated Pathway Database

Common Pathway of Fibrin Clot Formation (R-HSA-140875) [Homo sapiens]


The common pathway consists of the cascade of activation events leading from the formation of activated factor X to the formation of active thrombin, the cleavage of fibrinogen by thrombin, and the formation of cleaved fibrin into a stable multimeric, cross-linked complex. Thrombin also efficiently catalyzes the activation of several factors required earlier in the clotting cascade, thus acting in effect as a positive regulator of clotting. At the same time, thrombin activates protein C, which in turn catalyzes the inactivation of several of these upstream factors, thereby limiting the clotting process. Thrombin can be trapped in stable, inactive complexes with: antithrombin-III (SERPINC1), a circulating blood protein; heparin cofactor II (SERPIND1) which inhibits thrombin in a dermatan sulfateā??dependent manner in the arterial vasculature; protein C inhibitor (SERPINA5) that inhibits thrombin in complex with thrombomodulin; and Protease nexin-1 (SERPINE2) that inhibits thrombin at the vessel wall and platelet surface. The quantitative interplay among these positive and negative modulators is critical to the normal regulation of clotting, facilitating the rapid formation of a protective clot at the site of injury, while limiting and physically confining the process.
These events are outlined in the drawing: black arrows connect the substrates (inputs) and products (outputs) of individual reactions, and blue lines connect output activated enzymes to the other reactions that they catalyze.

Additional Information
Compartment extracellular region
GO Biological Process blood coagulation (0007596)
Cross References
Database Identifier
BioModels Database BIOMD0000000340, BIOMD0000000335, BIOMD0000000338, BIOMD0000000088, BIOMD0000000339
Literature References
pubMedId Title Journal Year
1931959 The coagulation cascade: initiation, maintenance, and regulation Biochemistry 1991