Usage
- Aprotinin + Fibrinogen + Thrombin is prescribed to control bleeding during surgical procedures when standard methods like sutures, ligatures, or cautery are ineffective or impractical. It also aids in tissue adhesion during skin grafting and cosmetic surgeries.
- Pharmacological Classification: Hemostatic agent, Fibrin sealant, Tissue adhesive.
- Mechanism of Action: This combination mimics the final steps of the physiological coagulation cascade. Thrombin converts fibrinogen into fibrin, forming a clot that adheres to the wound surface. Aprotinin, an antifibrinolytic, inhibits the premature breakdown of the fibrin clot, providing sustained hemostasis. Fibrinogen provides the necessary substrate for clot formation.
Alternate Names
- Fibrin Sealant
- Brand Names: TISSEEL, ARTISS, Beriplast P Combi-Set (regional variations exist)
How It Works
- Pharmacodynamics: Thrombin catalyzes the conversion of fibrinogen to fibrin, forming a stable clot which achieves hemostasis. Aprotinin preserves the clot by inhibiting plasmin, a key enzyme in fibrinolysis.
- Pharmacokinetics: The combination is applied topically; therefore, systemic absorption is minimal. The fibrin clot is gradually broken down and absorbed as part of the natural wound healing process. Aprotinin’s presence delays this fibrinolysis.
- Mode of Action: Thrombin directly acts on fibrinogen, cleaving specific peptides to form fibrin monomers, which polymerize to create a cross-linked fibrin clot. Aprotinin inhibits serine proteases, including plasmin, thereby preventing clot lysis.
- Receptor binding, enzyme inhibition, or neurotransmitter modulation: Thrombin interacts with fibrinogen as its substrate. Aprotinin acts as a serine protease inhibitor, primarily targeting plasmin.
- Elimination pathways: The fibrin clot is degraded and resorbed locally at the application site; minimal systemic involvement occurs. Residual aprotinin is minimally absorbed, partially metabolized and excreted renally.
Dosage
Standard Dosage
Adults: Dosage is determined by the size and characteristics of the application area and is at the surgeon’s discretion. Typical doses range from 0.5 mL to 4 mL, with larger volumes possible depending on the procedure (e.g., liver trauma, extensive burns).
Children: Pediatric dosing guidelines are not specifically established, however, data suggest similar efficacy and safety profiles compared to adult populations, especially in burn treatment. Use should be individualized based on the child’s weight, age, and specific clinical context. Pediatric safety considerations are crucial due to potential hypersensitivity reactions.
Special Cases:
- Elderly Patients: While specific geriatric studies are limited, clinical experience doesn’t indicate age-related dose modifications. Individualized assessment based on patient health and comorbid conditions is recommended.
- Patients with Renal Impairment: Dose adjustments are not typically needed due to minimal systemic absorption.
- Patients with Hepatic Dysfunction: Dose adjustments are not typically needed due to minimal systemic absorption.
- Patients with Comorbid Conditions: Careful evaluation and consideration of potential drug interactions are necessary, especially for patients with bleeding disorders or those receiving anticoagulants.
Clinical Use Cases
Dosage is adjusted based on the specific surgical need.
- Intubation: Not typically used.
- Surgical Procedures: Dose depends on the surgical site and the extent of bleeding.
- Mechanical Ventilation: Not applicable for this topical agent.
- Intensive Care Unit (ICU) Use: Applied as needed during surgical procedures performed in the ICU.
- Emergency Situations: Can be used in emergency surgery to control bleeding.
Dosage Adjustments
Dose adjustments are based primarily on the area of application and not on renal/hepatic function, metabolic disorders, or genetic polymorphisms.
Side Effects
Common Side Effects
- Procedural pain
- Nausea
- Constipation
- Incision site pain
- Fever
Rare but Serious Side Effects
- Hypersensitivity reactions (including anaphylaxis)
- Thromboembolic events (primarily with intravascular application)
- Air or gas embolism (when using spray applicators at high pressure or close proximity)
Long-Term Effects
- Antibody formation to aprotinin with repeated exposure.
- Granuloma formation at the application site (rare).
Adverse Drug Reactions (ADR)
- Anaphylaxis (rare but potentially life-threatening) requires immediate medical attention.
Contraindications
- Hypersensitivity to aprotinin, bovine proteins, or any component of the formulation.
- Intravascular application.
- Severe arterial bleeding.
Drug Interactions
- Anticoagulants and antiplatelet agents may increase the risk of bleeding; careful monitoring is required.
- Aprotinin can interact with certain medications used during cardiopulmonary bypass surgery.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Limited human data. Animal reproduction studies have not been conducted. Use only if clearly needed and the potential benefit justifies the potential risk to the fetus.
- Breastfeeding: Information regarding the presence of the drug in human milk is lacking. Weigh the potential benefits against the potential risks before breastfeeding during treatment.
Drug Profile Summary
- Mechanism of Action: Thrombin converts fibrinogen to fibrin, forming a clot; aprotinin inhibits fibrinolysis.
- Side Effects: Procedural pain, nausea, constipation, hypersensitivity reactions, thromboembolic events (with misuse).
- Contraindications: Hypersensitivity, intravascular application, severe arterial bleeding.
- Drug Interactions: Anticoagulants, antiplatelet agents.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
- Dosage: Determined by the area of application; ranges from 0.5 mL to 4 mL or more.
- Monitoring Parameters: Observe for bleeding, signs of hypersensitivity, and thromboembolic complications.
Popular Combinations
This product is generally used as a stand-alone combination of aprotinin, fibrinogen, and thrombin. It is not typically combined with other drugs in the same formulation.
Precautions
- Ensure proper topical application; avoid intravascular administration.
- Screen patients for hypersensitivity to components, especially aprotinin.
- Follow manufacturer guidelines strictly, particularly when using spray applicators.
- Closely monitor patients for bleeding, allergic reactions, and thromboembolic events.
- Exercise caution in pregnant or breastfeeding women.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Aprotinin + Fibrinogen + Thrombin?
A: The dose varies based on application site size, typically ranging from 0.5 mL to 4 mL. Larger volumes might be necessary for larger areas.
Q2: Can Aprotinin + Fibrinogen + Thrombin be used in children?
A: While specific pediatric guidelines are lacking, the combination has shown similar efficacy and safety profiles compared to adults in certain contexts like burn treatments. Careful individualised assessment is crucial.
Q3: What are the contraindications for this combination product?
A: Contraindications include hypersensitivity to any component, intravascular use, and severe arterial bleeding.
Q4: How does this combination work to stop bleeding?
A: Thrombin converts fibrinogen into fibrin, creating a clot, while aprotinin prevents premature clot breakdown.
Q5: What are the potential side effects?
A: Common side effects include procedural pain, nausea, and constipation. Rarely, serious hypersensitivity reactions or thromboembolic events can occur.
Q6: Can Aprotinin + Fibrinogen + Thrombin be injected?
A: No, it is exclusively for topical application. Intravascular injection is contraindicated and can cause thromboembolic complications.
Q7: Is it safe to use this drug during pregnancy or breastfeeding?
A: Limited human data is available. Use only when absolutely necessary and the benefits outweigh the potential risks to the fetus or neonate.
Q8: How is Aprotinin + Fibrinogen + Thrombin administered?
A: It’s applied topically by a healthcare professional during surgery.
Q9: Are there any drug interactions I should be aware of?
A: Concurrent use with anticoagulants or antiplatelet agents requires careful monitoring due to potential increased bleeding risks.
Q10: What should I monitor in a patient receiving this combination product?
A: Monitor for signs of bleeding, hypersensitivity reactions, and thromboembolic complications, especially after intravascular application (which should be avoided).
