What is fibrinogen?

Fibrinogen: A Critical Component in Hemostasis

Fibrinogen is a hepatically synthesized homodimer glycoprotein that plays a crucial role in blood coagulation as the final component in the coagulation cascade, serving as the precursor to fibrin which forms the structural scaffold of blood clots. 1

Molecular Structure and Composition

• Fibrinogen consists of two identical subunits, each formed by three non-identical polypeptide chains denoted Aα, Bβ, and γ, linked by 29 disulfide bridges, with a molecular weight of 340 kDa for the full-length protein 1
• The molecule has a half-life of 3-5 days in circulation and represents the most abundant coagulation factor in blood with normal plasma concentrations ranging from 2.0-4.0 g/L in non-pregnant patients 1, 2
• Approximately 75% of plasma fibrinogen is full-length fibrinogen, while 25% consists of degraded low molecular weight forms (305 or 270 kDa) that are less effective in promoting clotting 1

Physiological Function

• During hemostasis, thrombin cleaves fibrinopeptides A and B from the Aα and Bβ chains of fibrinogen, converting it to soluble fibrin monomers 1
• Fibrin monomers then polymerize and are cross-linked by factor XIII to form an insoluble fibrin clot that is resistant to fibrinolysis 1, 3
• Fibrinogen binds to the integrin receptor (αIIbβ3, also called glycoprotein IIb/IIIa) on activated platelets, acting as a bridge between platelets to facilitate platelet aggregation 1, 4
• Fibrinogen is the first coagulation factor to critically decrease (<1.0 g/L) during major hemorrhage due to consumption, dilution, and hyperfibrinolysis 1, 5

Clinical Significance

• Low fibrinogen levels impair fibrin clot strength and are associated with increased bleeding risk 1
• During massive blood loss replacement, fibrinogen is the first coagulation factor to critically decrease to levels below 1.0 g/L 1, 5
• In trauma patients, a decrease in fibrinogen concentration is a predictor of hemorrhage severity 1
• During postpartum hemorrhage, fibrinogen plasma concentration is the only coagulation parameter independently associated with progression to severe bleeding, with a level <2 g/L having a positive predictive value of 100% 1
• Elevated fibrinogen levels (>3.03 g/L) are associated with increased risk of myocardial infarction and stroke, with an odds ratio of 1.99 6

Measurement and Monitoring

• Fibrinogen measurement is usually performed in plasma according to the Clauss method, with a reference range of 1.8-3.5 g/L 1
• The Clauss method involves adding excess thrombin to a diluted sample, measuring clotting time mechanically or photo-optically, and comparing with a calibration curve 1
• Alternatively, immunological tests can measure total fibrinogen concentration rather than just the functionally active fibrinogen 1
• In trauma patients, a maximum clot firmness (MCF) of 7 mm using thromboelastometry corresponds to a fibrinogen level of approximately 2 g/L 1

Therapeutic Considerations

• Current guidelines recommend maintaining plasma fibrinogen levels above 1.5-2.0 g/L during significant bleeding 1
• Treatment with fibrinogen concentrate or cryoprecipitate is recommended when significant bleeding is accompanied by thromboelastometric signs of functional fibrinogen deficit or plasma fibrinogen levels below 1.5-2.0 g/L 1
• Fibrinogen administration using viscoelastic methods as guidance may be preferable to laboratory measurements of fibrinogen levels 1
• Fibrinogen concentrate provides rapid administration of standardized doses in small volumes compared to plasma or cryoprecipitate 5

Clinical Implications Beyond Hemostasis

• Fibrin(ogen) plays important roles in inflammation, wound healing, and tissue repair 3
• Abnormal fibrin deposits at sites including the central nervous system or kidney can be pathological 3
• Fibrinogen is an independent risk factor for both cardiac and extracardiac atherothrombotic complications 6

Understanding fibrinogen's critical role in hemostasis is essential for managing bleeding disorders, trauma, and surgical procedures where maintaining adequate fibrinogen levels can significantly impact patient outcomes.