Fibrinogen concentrate is a therapeutic product derived from human plasma, designed to treat severe bleeding by rapidly replacing a crucial clotting protein (Factor I). This protein is synthesized by the liver and serves as the structural foundation for blood clots. When a patient experiences acute, severe blood loss, the body’s natural supply of this clotting factor can become depleted through consumption and dilution from fluid resuscitation. The concentrate provides a standardized, high-dose source of Factor I, allowing clinicians to quickly restore the blood’s ability to form a strong, stable clot. This targeted approach stabilizes the patient’s clotting system without relying solely on less concentrated blood products.
The Role of Fibrinogen in Coagulation
Fibrinogen is the most abundant coagulation factor in blood plasma, providing the mechanical strength for a stable clot. The coagulation cascade culminates when the enzyme thrombin acts directly on soluble fibrinogen. Thrombin cleaves peptides from the fibrinogen molecule, transforming it into an insoluble protein called fibrin.
These newly formed fibrin monomers spontaneously link together, a process known as polymerization, creating long, interconnected strands. This extensive network of fibrin strands forms a meshwork that traps red blood cells and platelets at the site of vascular injury. Factor XIIIa then cross-links these strands, reinforcing the mesh to create a dense, durable clot that seals the wound.
A deficiency in fibrinogen concentration is often the first and most profound clotting factor abnormality seen during massive hemorrhage. Low levels lead to a fragile, weak clot that can easily break down, contributing to ongoing bleeding. Therapeutic replacement restores this structural component to maintain hemostasis.
Clinical Application of Fibrinogen Concentrate
Fibrinogen concentrate is administered to correct diagnosed or suspected deficiencies during periods of active, significant bleeding. This replacement strategy is valuable in cases of acquired hypofibrinogenemia, where the protein supply has been consumed or diluted. The concentrate is a component of massive transfusion protocols used in settings like severe trauma and complex surgical procedures.
Acquired Deficiencies
In trauma, rapid blood loss and subsequent volume replacement quickly dilute clotting factors, making fibrinogen a priority for early replacement. In complex cardiac surgery, particularly those involving cardiopulmonary bypass, the procedure can impair clotting function and lower fibrinogen levels. Early administration in these settings helps maintain hemostasis and may reduce the need for large volume transfusions.
A common scenario is obstetric hemorrhage, such as severe postpartum bleeding, where fibrinogen levels drop precipitously due to consumption. For most acquired deficiencies, guidelines suggest targeting a plasma fibrinogen level of at least 1.5 to 2.0 grams per liter (g/L) to support adequate clotting. However, a higher target of 2.0 g/L or greater is often recommended in obstetric hemorrhage due to the elevated baseline levels during pregnancy.
Congenital Deficiencies
The concentrate is also the established treatment for patients with rare, inherited congenital fibrinogen deficiencies, such as afibrinogenemia and hypofibrinogenemia. For these patients, it is used to treat acute bleeding episodes or prevent excessive bleeding during surgical procedures. For minor congenital bleeding events, the goal is typically to raise the fibrinogen level to 100 to 150 milligrams per deciliter (mg/dL). More serious bleeding events, such as intracranial hemorrhage, require a higher target level, often between 150 and 200 mg/dL.
Administration and Safety Profile
Fibrinogen concentrate is administered intravenously for rapid delivery directly into the bloodstream. Unlike cryoprecipitate, the concentrate is provided in a small, standardized volume, which is advantageous for patients at risk of fluid overload. The dose is determined based on the patient’s body weight and the degree of fibrinogen deficiency, often guided by laboratory measurements.
Monitoring treatment effectiveness involves laboratory tests to ensure the targeted fibrinogen level is achieved. Viscoelastic hemostatic assays (VHA), such as rotational thromboelastometry (ROTEM), offer near-immediate results assessing the functional quality and strength of the fibrin clot. Standard laboratory methods, like the Clauss fibrinogen test, provide a precise measurement of the total fibrinogen concentration in the plasma.
As a plasma-derived product, safety considerations exist, though modern manufacturing processes have significantly reduced risks. The most common serious concern is the potential for thromboembolism, or the formation of unwanted blood clots, since the product increases clotting ability. This risk is primarily associated with high doses or use in patients predisposed to clotting events.
Manufacturers employ rigorous screening of plasma donors and multiple viral inactivation steps, such as pasteurization, to minimize the risk of transmitting infectious agents. Patients are monitored for signs of allergic or hypersensitivity reactions, which can range from mild symptoms to a severe anaphylactic response.