Fibrinogen is a 340kDa hexameric plasma glycoprotein synthesized by the liver. There are three different genes on chromosome 4 which encode the synthesis of fibrinogen. The plasma concentration is approximately 200-400mg/dL. It has the maximum concentration amongst all the coagulation factors. It is the major structural component of a clot. The plasma half-life is three to four days. The minimum level required to maintain hemostasis is 100mg/dL.
The type of fibrinogen disorders that require replacement therapy can be congenital or acquired. There can be an abnormality in the amount or function of circulating fibrinogen. Classification of these disorders are as follows:
- Afibrinogenemia: An absence of circulating fibrinogen
- Hypofibrinogenemia: Reduced levels of circulating fibrinogen (<150mg/dL)
- Dysfibrinogenemia: Circulating fibrinogen is dysfunctional
- Hypodysfibrinogenemia: Circulating fibrinogen is reduced in quantity and is functionally abnormal
Indications for fibrinogen replacement therapy include the following conditions:
- Congenital disorders: The patients with congenital afibrinogenemia, hypofibrinogenemia, or dysfibrinogenemia presenting with clinically significant bleeding should be given fibrinogen concentrate to raise levels to 100-150mg/dL. However, a higher target of 150-200mg/dL is necessary for more severe bleeding (intracerebral bleeding). A target fibrinogen level of 50mg/dL is usually necessary for wound healing after achieving hemostasis.
- Massive trauma: The patients with severe trauma often present with massive hemorrhage, and impaired hemostasis. Retrospective studies have shown the reduced requirement of RBCs and platelets with the use of fibrinogen concentrates in patients with trauma.
- Disseminated intravascular coagulation (DIC): DIC is a syndrome characterized by widespread activation of intravascular coagulation leading to deposition of fibrin clots in blood vessels and organ failure. It can also present with bleeding manifestations due to the consumption of platelets and coagulation factors. The laboratory abnormality in DIC is thrombocytopenia, elevated fibrin degradation products, prolonged PT, aPTT, and low fibrinogen. The treatment for DIC includes fresh frozen plasma (FFP), platelets, packed red cells, cryoprecipitate, and fibrinogen concentrate depending on laboratory abnormalities. Severe hypofibrinogenemia (<100mg/dL) can be corrected with cryoprecipitate or fibrinogen concentrate after failed treatment with FFP with the target to keep levels above 100mg/dL.
- Liver diseases: It can correlate with both dysfibrinogenemia and hypofibrinogenemia. The abnormal fibrinogen has an increased amount of sialic acid that causes a delay in fibrin aggregation. It can present in various liver diseases like biliary obstruction, chronic liver disease, cirrhosis, and hepatoma. When the synthetic function is severely depressed in cases of advanced liver disease, it causes reduced production of fibrinogen.
- Cardiac surgery: The patients undergoing cardiovascular surgeries involving cardiopulmonary bypass often have peri-operative coagulopathic bleeding which requires transfusion of blood and blood products. The multiple risk factors affecting bleeding include the type of procedure, bypass time, re-operation, and comorbidities. Pre-operative fibrinogen levels appear to be an independent predictor of perioperative bleeding and transfusion requirement. Studies have reported the role of fibrinogen concentrate on reducing transfusion requirement in major aortic and coronary artery bypass graft surgeries.]
- Obstetric hemorrhage: The normal concentration of fibrinogen in the third trimester is close to 500mg/dL. The minimum amount of fibrinogen and other coagulation factors required for hemostasis is 40 to 50% and 20 to 25% of normal levels, respectively. Various studies have calculated the cutoff value of fibrinogen level less than 200mg/dL as a predictor of progression to massive blood loss and massive transfusion.