Usage
Fibrinogen + Thrombin is prescribed as an adjunct to hemostasis for mild-to-moderate bleeding in adults undergoing surgery when standard surgical techniques (e.g., suture, ligature, cautery) are ineffective or impractical. It is classified as a hemostatic agent and fibrin sealant. The medication mimics the final steps of the physiological coagulation cascade to achieve hemostasis.
Alternate Names
This combination product is commonly referred to as Fibrin Glue or Fibrin Sealant. Brand names include Raplixa, Evicel, TachoSil, and Veraseal.
How It Works
Pharmacodynamics: Fibrinogen and thrombin are combined to form a fibrin clot, mimicking the final step of the coagulation cascade. The resulting clot seals the bleeding site and promotes hemostasis. Aprotinin, sometimes included in fibrin sealant products, is an antifibrinolytic agent that inhibits the breakdown of the clot.
Pharmacokinetics: When applied topically, fibrinogen and thrombin react locally to form the fibrin clot. The clot is eventually broken down through the normal fibrinolytic processes. As a topical agent, it does not have systemic pharmacokinetics in the same way as oral or intravenous medications. Any small amount of the components absorbed does not contribute significantly to overall drug effects.
Mode of Action: Thrombin catalyzes the conversion of fibrinogen to fibrin monomers. These monomers polymerize to form a fibrin clot, which adheres to the surrounding tissue and provides hemostasis. Aprotinin, when included, prevents premature clot breakdown by inhibiting plasmin.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Thrombin acts as a serine protease, specifically cleaving fibrinogen. Aprotinin inhibits serine proteases involved in fibrinolysis, such as plasmin and kallikrein.
Elimination Pathways: The fibrin clot formed at the application site is broken down by the body’s natural fibrinolytic system. The byproducts are eliminated through the normal metabolic pathways.
Dosage
Standard Dosage
Adults: The dose varies based on the size of the bleeding area, not exceeding a total of 3g per surgery.
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Direct application: 0.5g for up to 25 cm², 1g for up to 50 cm², and 2g for up to 100 cm².
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Spray application: 0.5g for up to 50 cm², 1g for up to 100 cm², and 2g for up to 200 cm².
Children: Safety and efficacy in pediatric patients have not been established.
Clinical Use Cases
Dosage in specific clinical situations follows the general adult dosage guidelines and is adjusted according to the size of the bleeding area:
- Intubation: Not specifically indicated.
- Surgical Procedures: Follow general adult guidelines.
- Mechanical Ventilation: Not specifically indicated.
- Intensive Care Unit (ICU) Use: Follow general adult guidelines.
- Emergency Situations: Follow general adult guidelines.
Dosage Adjustments
Dosage adjustments are based on the bleeding area size. Considerations for organ dysfunction and other patient-specific factors are based on clinician judgment.
Side Effects
Common Side Effects:
Procedural pain, nausea, constipation, incision site pain, fever, anemia, vomiting, hypotension, itching, hypertension, and antithrombin antibodies.
Rare but Serious Side Effects:
Allergic reactions (hives, generalized urticaria, tightness of chest, wheezing, hypotension, and anaphylaxis), thromboembolic events (especially with intravascular application), and air or gas embolism (with spray application).
Long-Term Effects: Not typically associated with long-term adverse effects as it is a topical application.
Contraindications
- Intravascular application
- Severe or brisk arterial bleeding
- Known anaphylactic or severe systemic reactions to human blood products
Drug Interactions
No significant drug interactions are specifically listed. However, caution should be used when given concomitantly with other medications.
Pregnancy and Breastfeeding
Animal reproduction studies have not been conducted. Its use during pregnancy and breastfeeding should be considered only if clearly needed. It is unknown if it is excreted in breast milk.
Drug Profile Summary
- Mechanism of Action: Mimics final steps of coagulation cascade, converting fibrinogen to fibrin to form a clot.
- Side Effects: Procedural pain, nausea, constipation, incision site pain, fever, anemia, hypotension, hypertension, itching, and rare but serious allergic reactions or thromboembolic events.
- Contraindications: Intravascular application, severe arterial bleeding, hypersensitivity to human blood products.
- Drug Interactions: No significant drug interactions listed.
- Pregnancy & Breastfeeding: Safety not established. Use only if clearly needed.
- Dosage: Varies by bleeding area size, not exceeding 3g per surgery. Not established for pediatric patients.
- Monitoring Parameters: Observe for signs of bleeding, allergic reaction, and thromboembolic events. Monitor fibrinogen levels as needed.
Popular Combinations
Often used with absorbable gelatin sponge. Some formulations include aprotinin to inhibit fibrinolysis.
Precautions
- Ensure proper topical application and avoid intravascular administration.
- Follow manufacturer’s instructions, especially when using spray applicators to reduce the risk of air embolism.
- Screen for allergies to human blood products.
- Closely monitor patients for hypersensitivity reactions during and after application.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fibrinogen + Thrombin?
A: The dose depends on the size of the bleeding area, not exceeding a total of 3g per surgery. For direct application: 0.5g for up to 25 cm², 1g for up to 50 cm², and 2g for up to 100 cm². For spray application: 0.5g for up to 50 cm², 1g for up to 100 cm², and 2g for up to 200 cm². Pediatric dosage has not been established.
Q2: How is Fibrinogen + Thrombin administered?
A: It is applied topically directly to the bleeding surface during surgery, either directly from the vial or using a spray applicator.
Q3: What are the contraindications to using Fibrinogen + Thrombin?
A: Contraindications include intravascular application, severe or brisk arterial bleeding, and known hypersensitivity to human blood products.
Q4: What are the potential side effects of Fibrinogen + Thrombin?
A: Common side effects include procedural pain, nausea, and constipation. Rare but serious side effects include allergic reactions (including anaphylaxis) and thromboembolic events.
Q5: Can Fibrinogen + Thrombin be used in pregnant or breastfeeding women?
A: Safety in pregnancy and breastfeeding has not been established. Use only if clearly needed and after careful risk-benefit assessment.
Q6: How does Fibrinogen + Thrombin work to stop bleeding?
A: Thrombin converts fibrinogen to fibrin, creating a clot that seals the bleeding area. Some formulations include aprotinin, which helps stabilize the clot by preventing its breakdown.
Q7: What precautions should be taken when using Fibrinogen + Thrombin in patients with hepatic or renal impairment?
A: While specific dosage adjustments are not listed for these patient populations, careful clinical judgment is advised considering the patient’s bleeding severity, overall condition, and potential for complications. Close monitoring of these patients is critical.
Q8: Are there any drug interactions I should be aware of with Fibrinogen + Thrombin?
A: No significant drug interactions are listed, however, this does not preclude the possibility of interactions. Consult with a specialist as needed.
Q9: What is the role of aprotinin in some Fibrinogen + Thrombin products?
A: Aprotinin is an antifibrinolytic agent that inhibits the breakdown of the fibrin clot, contributing to prolonged hemostasis.
