Thrombin

Usage

Thrombin is prescribed as a topical hemostatic agent to control oozing blood and minor bleeding from capillaries and small venules when standard surgical techniques are ineffective or impractical. It is frequently used in various surgical settings such as spinal surgery, hepatic resection, peripheral arterial bypass surgery, arteriovenous graft formation for hemodialysis access, plastic surgery, dental extractions, and skin grafting. Its pharmacological classification is hemostatic agent (coagulation factor). Thrombin’s mechanism of action involves converting fibrinogen to fibrin, which is essential for blood clot formation.

Alternate Names

Thrombin is also known as Thrombin, Topical (Human) and Thrombin, Topical (Bovine). Brand names include Evithrom, Recothrom, Thrombogen, Thrombin-JMI, Thrombinar, and Thrombostat. Other preparations containing Thrombin may have other names, such as Floseal, Surgiflo, Thrombi-Gel, and Thrombi-Pad.

How It Works

Pharmacodynamics: Thrombin’s primary effect is to promote hemostasis by converting fibrinogen to fibrin, the building block of blood clots. It acts locally at the application site.

Pharmacokinetics: When applied topically, minimal systemic absorption is expected. Any absorbed thrombin is rapidly inactivated in the circulation. Elimination pathways for systemically absorbed thrombin are not fully characterized but would likely involve hepatic and renal mechanisms.

Mode of Action: Thrombin, a serine protease, directly cleaves fibrinogen to form fibrin monomers. These monomers polymerize to form a fibrin clot, which helps stop bleeding. Thrombin also activates platelets, further enhancing clot formation. It does not bind to specific receptors but acts directly on fibrinogen. Elimination is primarily local via enzymatic degradation within the formed clot, with minimal systemic involvement under normal use.

Dosage

Standard Dosage

Adults: Dosage depends on the area of bleeding and the method of application. Standard preparations may range from 100-2000 IU/mL. For profuse bleeding from surfaces such as liver or spleen, concentrations of 1000 IU/mL may be necessary. For general surgical use, concentrations of 100 IU/mL are often sufficient. The solution can be sprayed, or the surface may be flooded using a sterile syringe and needle. Thrombin can also be applied in dry form to oozing surfaces.

Children: Safety and efficacy in children have not been fully established. For children over 1 month of age, the dose is dependent on the treatment area. Consultation with a pediatric specialist is recommended.

Special Cases:

• Elderly Patients: No specific dosage adjustments are required, but caution should be exercised due to potential age-related organ dysfunction.

• Patients with Renal Impairment: No specific dosage adjustments indicated for topical use.

• Patients with Hepatic Dysfunction: No specific dosage adjustments indicated for topical use.

• Patients with Comorbid Conditions: Consider underlying bleeding disorders and potential drug interactions.

Clinical Use Cases:

Dosing follows standard adult recommendations adjusted to the specific bleeding site and severity. Systemic injection is contraindicated.

• Intubation: Not applicable for intubation procedures.

• Surgical Procedures: Commonly used to control capillary and small venule bleeding.

• Mechanical Ventilation: Not applicable for mechanical ventilation.

• Intensive Care Unit (ICU) Use: As needed for topical hemostasis during procedures or for managing bleeding complications.

• Emergency Situations: As needed for topical hemostasis.

Dosage Adjustments: Dosage should be titrated based on the extent and severity of bleeding.

Side Effects

Common Side Effects:

Allergic reactions (especially to bovine-derived products), fever, procedural pain, nausea, and vomiting.

Rare but Serious Side Effects:

Hypersensitivity reactions, bleeding, anemia, postoperative wound infection, thromboembolic events, hypotension, tachycardia, thrombocytopenia, thrombosis, and antibody formation (especially with bovine thrombin), disseminated intravascular coagulation (DIC), and anaphylaxis.

Long-Term Effects: Not applicable for topical application, unless systemic absorption occurs.

Adverse Drug Reactions (ADR):

Anaphylaxis, thrombosis, and DIC.

Contraindications

Hypersensitivity to thrombin (human or bovine), known antibodies to bovine thrombin or factor V. Systemic injection is absolutely contraindicated due to the risk of thrombosis.

Drug Interactions

Few clinically significant drug interactions are known for topical thrombin. However, it may theoretically interact with anticoagulants. It is crucial to inform the patient’s doctor about all medications and supplements the patient is taking.

Pregnancy and Breastfeeding

Pregnancy Safety Category C. Animal studies have not been conducted. Human data are limited. Use only if clearly needed, weighing benefits against risks. It is unknown if thrombin is excreted in breast milk. Caution is advised.

Drug Profile Summary

• Mechanism of Action: Converts fibrinogen to fibrin, promoting clot formation.
• Side Effects: Allergic reactions, fever, bleeding complications, thrombosis, DIC.
• Contraindications: Hypersensitivity to thrombin, systemic injection.
• Drug Interactions: Limited data, potential interaction with anticoagulants.
• Pregnancy & Breastfeeding: Category C, caution advised.
• Dosage: Topical application 100-2000 IU/mL depending on the clinical scenario.
• Monitoring Parameters: Observe bleeding site for hemostasis and signs of complications. Monitor coagulation parameters if systemic absorption is suspected.

Popular Combinations

Thrombin is often used in combination with absorbable gelatin sponges or hemostatic matrices. These provide a scaffold for clot formation and enhance hemostasis.

Precautions

• General Precautions: Evaluate for allergies, bleeding disorders, and pre-existing antibodies (especially for bovine thrombin). Avoid systemic administration.
• Specific Populations:
  • Pregnant Women: Use with caution only if clearly needed.
  • Breastfeeding Mothers: Caution is advised; the risk of neonatal exposure is unknown.
  • Children & Elderly: Use with caution, adjusting dosage as needed.
  • Menstruating Individuals: No specific precautions.
• Lifestyle Considerations: No specific lifestyle restrictions associated with topical use.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Thrombin?

A: The dosage varies based on the clinical setting, from 100 IU/mL for general use to 1000 IU/mL or higher for profuse bleeding.

Q2: How is Thrombin administered?

A: Topically applied as a solution or powder, or in combination with a matrix. Never inject directly into the circulatory system.

Q3: What are the major contraindications for Thrombin?

A: Hypersensitivity, known antibodies (especially to bovine thrombin), and systemic injection.

Q4: What are the potential side effects of Thrombin?

A: Allergic reactions, bleeding, thrombosis, and (rarely) DIC and anaphylaxis.

Q5: Can Thrombin be used in pregnant or breastfeeding women?

A: Use with caution only if clearly needed. Safety data are limited. It is unknown if it is excreted in breast milk.

Q6: What is the difference between bovine and human thrombin?

A: Bovine thrombin carries a higher risk of antibody formation, which can lead to bleeding or thrombotic complications. Human thrombin is generally preferred due to its lower immunogenicity.

Q7: How does Thrombin work at the molecular level?

A: It cleaves fibrinogen to form fibrin monomers, leading to fibrin clot formation and platelet activation.

Q8: What are the clinical uses of Thrombin?

A: Primarily used for hemostasis during surgical procedures, especially for controlling capillary and small venule bleeding.

Q9: What precautions should be taken when administering Thrombin?

A: Always apply topically, avoid systemic administration. Be aware of potential hypersensitivity reactions, especially with bovine-derived products.

Q10: Are there any drug interactions I should be aware of?

A: Though limited data are available regarding drug interactions for topical application, it’s essential to consider potential interactions with anticoagulants and consult a specialist if there is ambiguity. Monitor the patient for potential adverse effects.