Fibrinogen: Effect on Coagulation

Fibrinogen, also known as Factor I of the coagulation cascade, is a soluble plasma protein synthesized in the liver and converted into insoluble fibrin in the final phase of blood coagulation. An adequate fibrinogen concentration is essential for the formation of a stable blood clot. As a medicinal product, fibrinogen is derived from human donor plasma, highly purified, virus-inactivated, and available in lyophilized form for substitution (brand names Fibryga, Riastap, Haemocomplettan and others).

In Germany, fibrinogen is one of the classic drugs in emergency and transfusion medicine. It has an established role in massive hemorrhage, postpartum hemorrhage, congenital afibrinogenemia, and cardiac surgery. The indication for administration is usually clear (hypofibrinogenemia below 1.5 to 2 g per liter during active bleeding). Careful diagnostics with coagulation tests, fibrinogen measurement, and where appropriate, thromboelastometry help to guide substitution purposefully.

Mechanism of Action

In the coagulation cascade, the enzyme thrombin (Factor IIa) cleaves fibrinogen into fibrin monomers. These polymerize spontaneously into an unstable network, which is subsequently covalently cross-linked by activated Factor XIII. This creates a stable fibrin clot, which additionally reinforces the primary hemostasis from platelet plug and achieves definitive hemostasis.

During acute bleeding, fibrinogen is one of the first factors to fall below the critical threshold. Studies in trauma and postpartum bleeding patients show that early substitution can reduce blood loss and lower mortality. The effect of substitution occurs immediately because the administered fibrinogen enters the coagulation cascade directly.

Pharmacokinetically, fibrinogen has a half-life of approximately three to five days. A single dose can raise the plasma level by approximately 1 g per liter per 60 mg per kg of body weight. The substance is broken down in the reticuloendothelial system; renal elimination plays no role.

Areas of Application

• Acquired hypofibrinogenemia in acute massive hemorrhage, such as in trauma, polytrauma, or major surgical procedures
• Postpartum hemorrhage with marked fibrinogen decline, often in the context of uterine atony, placental abruption disorders, or amniotic fluid embolism
• Disseminated intravascular coagulation (DIC) in consumptive coagulopathy
• Cardiac surgery with cardiopulmonary bypass, when fibrinogen values fall below the critical range
• Liver disease with synthetic insufficiency and bleeding manifestations
• Congenital fibrinogen disorders such as afibrinogenemia, hypofibrinogenemia, and dysfibrinogenemia, including substitution prior to invasive procedures or in manifest bleeding

Fibrinogen is not suitable for prophylactic use without indication. Even in elective surgery, administration alone without hypofibrinogenemia is not recommended because thromboembolic events are possible.

Dosage and Administration

Acute hemorrhage: Initial dose 30 to 60 mg per kg body weight intravenously, further dosing according to fibrinogen level and clinical course. The goal is usually plasma fibrinogen above 1.5 to 2 g per liter; in postpartum hemorrhage, often above 2 g per liter is targeted.

Postpartum hemorrhage: Often 2 to 4 g initially, early in the treatment algorithm, supplementary to tranexamic acid and massive transfusion protocol.

Cardiac surgery: Control via fibrinogen measurement or thromboelastometry, bolus 25 to 50 mg per kg, repeat if necessary.

Congenital afibrinogenemia: Regular substitution or on-demand substitution before procedures, target level above 1 g per liter. During pregnancy, often higher target values (above 1.5 g per liter).

Administration: Powder dissolved in water for injection (volume reconstitution according to product information), slow intravenous infusion, no bolus faster than 5 ml per minute. If symptoms such as shortness of breath, circulatory reaction, or rash appear, stop infusion.

Renal insufficiency and hepatic insufficiency: As a rule, no dose adjustment is required because fibrinogen is an endogenous protein. In liver disease with coagulation disorder, the requirement may be higher.

Side Effects

Frequent: Fever, chills, nausea, mild skin redness, headache.

Occasional: Allergic reactions including anaphylaxis, local reaction at infusion site.

Rare, but relevant: Thromboembolic complications, especially with rapid level elevation, in higher doses, or in predisposed patients (obesity, trauma, cardiovascular disease). With hyperfibrinogenemia, the risk of thrombosis increases.

Transmission of pathogens: Fibrinogen concentrates from plasma are highly purified and undergo multiple virus inactivation steps. The residual risk is very low, but theoretically cannot be completely ruled out.

Antibody formation: Very rare in congenital afibrinogenemia after repeated substitution.

Interactions

• Antifibrinolytics (tranexamic acid, aprotinin): synergistic effect in hemostasis desired, combination frequent.
• Anticoagulants (heparin, DOAC, vitamin K antagonists): in active bleeding, ideally antagonize or pause, because otherwise fibrinogen substitution is limited in effect.
• Thrombolytics (alteplase, tenecteplase): destroy fibrin network, fibrinogen substitution may be necessary after lysis therapy.
• Other coagulation factors (fresh plasma, factor concentrates): combination within massive transfusion protocols.
• Red blood cell concentrates and platelets: can be used together in massive transfusion.

Special Notes

Pregnancy: Can be used in vital indication, especially life-saving in postpartum hemorrhage. Prophylactic substitution without clear indication is not recommended. Lactation: Substitution during lactation is usually acceptable, individual assessment required.

Children: Established in pediatric emergency medicine, dose adapted to weight.

Before use: Determine fibrinogen level, take history of known allergies, previous reactions, cardiovascular disease, thromboembolic risks. In emergencies, initial administration is often empirical, level measurement during course is mandatory.

Monitoring: Plasma fibrinogen before and after substitution, every 30 to 60 minutes in acute phase, less frequently with stable course. Concurrently INR, aPTT, platelets, hemoglobin, clinical status.

Avoid hyperfibrinogenemia: In patients with increased thromboembolic risk, control purposefully, do not elevate level unnecessarily above target. Supplementary mechanical thromboprophylaxis individualized.

Storage: Store lyophilisate at room temperature, use solution after reconstitution quickly, refrigerator only allowed for individual products.

Ability to drive: Not directly relevant because use occurs in acute situations.

You May Also Be Interested In

• Heparin, anticoagulant for thromboprophylaxis and therapy
• Warfarin, vitamin K antagonist for oral anticoagulation
• Clopidogrel, platelet aggregation inhibitor in secondary prevention
• Phytomenadion, vitamin K1 to reverse the effect of vitamin K antagonists
• Noradrenaline, vasopressor in emergency medicine

Frequently Asked Questions

Sources

• Gelbe Liste, Fibrinogen active ingredient profile
• BfArM, Federal Institute for Drugs and Medical Devices
• AWMF, Guidelines on massive transfusion and postpartum hemorrhage
• German Society for Transfusion Medicine