What is Fibrinogen?
Fibrinogen is a large glycoprotein synthesized primarily in the liver that serves as the most abundant coagulation factor in blood and the essential precursor protein for fibrin clot formation during hemostasis. 1
Molecular Structure
- Fibrinogen consists of two identical subunits, each formed by three non-identical polypeptide chains (Aα, Bβ, and γ) linked by 29 disulfide bridges, with a molecular weight of 340 kDa. 1
- The molecule has a half-life of 3-5 days in circulation. 1
- Approximately 75% of plasma fibrinogen is full-length, while 25% consists of degraded low molecular weight forms (305 or 270 kDa) that are less effective in promoting clotting. 1
Normal Plasma Concentrations
- Normal plasma concentrations range from 1.5-4.0 g/L in healthy non-pregnant individuals. 1, 2
- Fibrinogen is the third most abundant soluble protein in human plasma and is also stored in platelet granules. 3
Physiological Role in Hemostasis
Fibrinogen plays two critical roles in blood clotting:
Fibrin formation: Thrombin cleaves fibrinopeptides A and B from the Aα and Bβ chains of fibrinogen, converting it to soluble fibrin monomers that then polymerize and are cross-linked by factor XIII to form an insoluble fibrin clot resistant to fibrinolysis. 1
Platelet aggregation: 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
Fibrinogen is the final component in the coagulation cascade and the ligand for platelet aggregation, making it key to effective coagulation and platelet function. 3
Clinical Significance in Bleeding
Fibrinogen is the first coagulation factor to critically decrease during major hemorrhage:
During massive blood loss replacement, fibrinogen is the first coagulation factor to critically decrease to levels below 1.0 g/L due to consumption, dilution, and hyperfibrinolysis. 1
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%. 3, 1
Low fibrinogen levels impair fibrin clot strength and are associated with increased bleeding risk. 1
Measurement
- 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
- 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 Thresholds
Current guidelines recommend maintaining plasma fibrinogen levels above 1.5-2.0 g/L during significant bleeding. 3, 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. 3, 1
An initial fibrinogen concentrate dose of 3-4 g or 50 mg/kg of cryoprecipitate (approximately equivalent to 15-20 single donor units in a 70 kg adult) is suggested, with repeat doses guided by viscoelastic monitoring and laboratory assessment. 3