Fibrinogen

Fibrinogen, also known as coagulation factor I, is a soluble glycoprotein essential to hemostasis. In human plasma it circulates at about 2 to 4 g/L and serves as the precursor of fibrin, the insoluble polymer that forms a blood clot. It is synthesized by hepatocytes.

It is a 340 kDa protein consisting of six polypeptide chains—two identical sets of Aα, Bβ, and γ—that assemble into a central E region and two outer D domains. This structure provides binding sites for thrombin, platelets, and other coagulation factors.

Activation and function: Thrombin cleaves fibrinopeptides A and B from fibrinogen, producing soluble fibrin monomers that rapidly polymerize into an insoluble fibrin network. Factor XIIIa crosslinks fibrin strands to stabilize the clot, while interactions with platelet receptors help initiate aggregation.

Clinical relevance: Fibrinogen is an acute-phase reactant; levels rise with inflammation, infection, pregnancy, and tissue injury. Low levels occur with congenital afibrinogenemia or hypofibrinogenemia and with acquired conditions such as severe liver disease, disseminated intravascular coagulation, or massive transfusion. Dysfibrinogenemia denotes qualitative defects in fibrinogen function. High levels are associated with inflammatory states and cardiovascular risk.

Testing and treatment: Fibrinogen can be measured functionally by the Clauss assay or quantitatively by immunoassays. In deficiency states, replacement with fibrinogen concentrate or cryoprecipitate can restore hemostasis.