Primary Site of Synthesis
The liver is the sole major source of fibrinogen synthesis in the body, with hepatocytes responsible for producing this essential coagulation factor under both basal and inflammatory conditions. 1, 2, 3
Fibrinogen is synthesized as a large 340 kDa glycoprotein and secreted into the bloodstream, where it circulates at concentrations of 1.5-4.0 g/L in healthy individuals. 2, 3
The normal half-life of circulating fibrinogen is approximately 3-5 days in healthy individuals, though this is shortened in conditions like cirrhosis. 1, 2
Regulation of Production
Fibrinogen synthesis is regulated at both transcriptional and translational levels, with constitutive (basal) secretion occurring continuously from the liver. 4
Production can be upregulated significantly during acute inflammatory responses, as fibrinogen functions as an acute-phase reactant that can increase several-fold in response to injury, infection, or inflammatory stimuli. 1, 4
Extrahepatic Production
While the liver accounts for approximately 98% of fibrinogen synthesis, low levels of fibrinogen expression have been detected in extrahepatic tissues, including certain carcinomas and differentiated intestinal epithelial cells. 1, 5
In the intestine specifically, a subset of differentiated epithelial cells constitutively produces fibrinogen that is deposited at the basement membrane as fibrin, where it serves as a substrate for wound healing under both physiological and pathological conditions. 5
However, these extrahepatic sources contribute minimally to circulating fibrinogen levels and are primarily relevant for local tissue function rather than systemic hemostasis. 5
Clinical Implications
Because fibrinogen is predominantly liver-derived, patients with advanced liver disease often develop hypofibrinogenemia due to decreased hepatic synthetic function. 1
In cirrhosis, fibrinogen levels are usually normal in compensated disease but often decrease in end-stage liver disease, reflecting the severity of hepatic dysfunction. 1, 6