From the Guidelines
Fibrinogen is a crucial protein produced by the liver that plays a central role in blood clotting, with normal levels ranging from 200-400 mg/dL, and its deficiency can lead to bleeding disorders, while high levels are associated with increased risk of blood clots. Fibrinogen is converted to fibrin when an injury occurs, forming a mesh-like structure that traps platelets and other blood cells to create a clot and stop bleeding. Low fibrinogen levels can be caused by certain conditions like liver disease, severe infections, or disseminated intravascular coagulation (DIC), and in medical settings, fibrinogen concentrate or cryoprecipitate may be administered to patients with dangerously low fibrinogen levels to prevent or treat bleeding, as seen in studies such as 1. The critical minimum concentration of fibrinogen required to maintain haemostasis is a matter of debate, but plasma fibrinogen levels less than approximately 100 mg/dl are associated with spontaneous and procedure-related bleeding in patients with cirrhosis, as noted in 1. In patients with cirrhosis, a fibrinogen threshold from 100 to 200 mg/dl has been recommended to trigger fibrinogen replacement in the setting of bleeding, with a commonly agreed upon cut-off of >120 mg/dl, as discussed in 1. Fibrinogen production and degradation in patients with decompensated cirrhosis remains poorly understood, with some authors proposing that low levels of fibrinogen are more indicative of decreased hepatic production, while others propose that low-grade intravascular coagulation contributes to low levels of fibrinogen in cirrhosis, as mentioned in 1. In vitro data showed that fibrinogen levels of >100 mg/dl resulted in greater mechanical clot stability compared to lower levels of fibrinogen, as seen in 1. Some studies, such as 1, have compared cryoprecipitate with fibrinogen concentrate, noting that fibrinogen concentrate has a lower volume and lacks the need for cross-matching, making it a favorable option in certain situations. However, the effectiveness of fibrinogen replacement in preventing or treating bleeding in patients with cirrhosis is still a topic of debate, with some studies, such as 1, failing to demonstrate a beneficial effect of preemptive fibrinogen administration. Overall, fibrinogen's essential function in hemostasis makes it a critical component of our body's defense against blood loss, and its measurement and replacement are important considerations in medical settings, particularly in patients with cirrhosis or other conditions that may affect fibrinogen levels, as discussed in 1 and 1.
From the Research
Definition and Function of Fibrinogen
- Fibrinogen is a large glycoprotein synthesized primarily in the liver, with a normal plasma concentration of 1.5-4 g/L 2, 3.
- It is the most abundant blood coagulation factor and plays a crucial role in the formation of a stable blood clot, containing polymerized and cross-linked fibrin, to prevent blood loss and drive wound healing upon vascular injury 2, 3.
- Fibrinogen is converted to fibrin by thrombin-mediated cleavage, and the formation of a stable blood clot is essential for hemostasis and the development and outcome of thrombotic complications 3.
Role of Fibrinogen in Disease
- Disruption of the equilibrium between clotting and fibrinolysis can cause disease, and altered levels of fibrinogen can lead to pathological conditions 2.
- Low levels of fibrinogen expression have been detected in extra-hepatic tissues, including carcinomas, potentially contributing to disease 2.
- Fibrin(ogen) deposits at aberrant sites, including the central nervous system or kidney, can also be pathological 2.
Treatment and Management of Fibrinogen-Related Disorders
- Replacement therapy is the mainstay of treatment of bleeding episodes in patients with congenital fibrinogen deficiency, and plasma-derived fibrinogen concentrate is the agent of choice 4, 5.
- Cryoprecipitate and fresh frozen plasma are alternative treatments that should be used only when fibrinogen concentrate is not available 4, 6.
- Human fibrinogen concentrate has made it the preferred replacement alternative due to its reduced risk of viral transmission, smaller infusion volume, and accurate dosing 5.