Fibrinogen (coagulation Factor I) is a protein produced by the liver that is necessary for blood clotting. It circulates in the blood until an injury occurs, where the enzyme thrombin converts it into insoluble fibrin strands. These strands form the meshwork of a stable blood clot. When the concentration of this protein falls below the normal range, a condition called hypofibrinogenemia, the ability to form a strong clot is impaired, increasing the risk of hemorrhage. The complete absence of the protein is a rarer condition termed afibrinogenemia. Management involves identifying the underlying cause and replacing the missing protein to restore normal clotting function.
Understanding the Causes of Low Fibrinogen
Low fibrinogen levels are categorized as either inherited or acquired. Inherited fibrinogen disorders are rare, lifelong genetic conditions resulting from gene mutations. These include afibrinogenemia (complete absence of fibrinogen) and hypofibrinogenemia (reduced levels of functional protein). Dysfibrinogenemia is a third form involving a dysfunctional protein that does not clot properly.
Acquired hypofibrinogenemia is far more common, often developing secondary to another medical issue. A primary cause is severe liver disease, such as cirrhosis or acute liver failure, since the liver synthesizes fibrinogen. In these cases, the liver fails to produce sufficient protein or creates a functionally abnormal version.
Increased consumption or destruction of the protein is another major cause. This occurs in conditions like Disseminated Intravascular Coagulation (DIC), where uncontrolled clotting consumes fibrinogen faster than it can be produced. Low levels also result from massive hemorrhage and subsequent resuscitation with intravenous fluids and red blood cells. This dilutional effect lowers the overall concentration of clotting factors in the blood.
Diagnosis and Assessment
Low fibrinogen is confirmed and monitored through specialized blood tests measuring its concentration and functional capacity. The definitive test is the Fibrinogen Activity Assay, often using the Clauss method. This assay measures the time required for a clot to form after adding a high concentration of thrombin to the patient’s plasma. The resulting clotting time accurately calculates the functional level of fibrinogen present.
Global coagulation tests, such as the Prothrombin Time (PT) and the Activated Partial Thromboplastin Time (aPTT), support the diagnosis. These tests measure the overall time it takes for blood to clot through different pathways. In severe deficiency, both the PT and aPTT are typically prolonged because fibrinogen is the final common step in the clotting cascade. Since these tests are non-specific, the Clauss assay is necessary for a precise diagnosis and guiding replacement therapy decisions.
Immediate Treatment Options
The core strategy for treating low fibrinogen in acute situations is replacement therapy, rapidly delivering the missing protein to the bloodstream. The product choice depends on availability, urgency, and the presence of other coexisting factor deficiencies. Two main products are used: cryoprecipitate and fibrinogen concentrate.
Cryoprecipitate is a blood bank product derived from fresh frozen plasma, rich in fibrinogen, Factor VIII, Factor XIII, and von Willebrand factor. It has historically been the standard treatment for acquired hypofibrinogenemia, especially in trauma or massive bleeding. Since it requires thawing and pooling multiple donor units before administration, it can introduce a delay in treatment.
Fibrinogen concentrate, a pharmaceutical product, offers several logistical and safety advantages. It is prepared as a lyophilized powder, allowing for rapid reconstitution and administration without thawing or blood type matching. The manufacturing process includes viral inactivation, significantly reducing the risk of transmitting infectious agents. This product provides a standardized, high dose of fibrinogen, making it the preferred option for many patients with inherited deficiencies.
The dose is carefully calculated based on the patient’s weight and current fibrinogen level to achieve a specific target. For acute, life-threatening hemorrhage (e.g., major trauma or postpartum bleeding), guidelines recommend raising the level above 150 mg/dL (1.5 g/L). For less severe bleeding or chronic deficiencies, a target level over 100 mg/dL (1.0 g/L) is usually adequate to maintain hemostasis.
Treating the underlying cause is necessary for acquired deficiency management. For instance, transfusing red blood cells and platelets helps address volume loss and other clotting deficits during massive hemorrhage. However, the priority in all acute bleeding cases remains the rapid normalization of fibrinogen levels to stabilize the clot and control the hemorrhage.
Long-Term Management and Prevention
Long-term management focuses on regular monitoring and proactive measures to prevent bleeding, especially for individuals with congenital fibrinogen disorders. Patients with severe inherited deficiencies may receive prophylactic treatment, involving scheduled, routine infusions of fibrinogen concentrate. This regular administration aims to maintain a baseline protein level sufficient to prevent spontaneous bleeding.
These patients require consistent follow-up with a hematologist to monitor levels and adjust the prophylactic regimen as needed. Regular blood tests ensure the functional protein level remains within the therapeutic range set by the physician. Maintaining this stable level minimizes the cumulative damage caused by recurrent, small bleeds.
Management also requires careful pre-planning for high-risk situations, such as surgery, pregnancy, or significant trauma. Before any planned procedure, the medical team temporarily increases treatment intensity to ensure fibrinogen levels are well above the standard threshold. This temporary boost provides maximum protection against excessive bleeding during the procedure and recovery.