Introduction

Hemostatic agent.

Uses for Thrombin

Hemorrhage

Aids hemostasis at accessible sites of oozing blood and minor bleeding from capillaries and small venules. In various types of surgery, may be used in conjunction with an absorbable gelatin sponge.

Does not control arterial bleeding when used alone.

Thrombin Dosage and Administration

General

• The concentration of thrombin solutions used depends on the severity of bleeding.

Administration

Topical Administration

Apply topically as a powder or solution; do not inject.

Prepare and administer solution according to manufacturer's recommendations. Use solution promptly upon removal from container.

Spray reconstituted solution directly onto bleeding surfaces (using a sterile syringe and spray tip, spray pump and actuator, or nasal delivery device) or apply with an absorbable gelatin sponge; do not leave solution in syringe as an intermediate step when preparing the spray delivery device.

Alternatively, flood surfaces with thrombin solution using a sterile syringe and small gauge needle. To avoid inadvertent intravascular administration, label syringes containing reconstituted thrombin (bovine) with a warning against IV injection and keep separate from parenteral preparations.

May apply as a dry powder; preferred method of application to oozing surfaces in some cases.

May use in conjunction with a bovine gelatin-based hemostatic matrix (e.g., FloSeal NT).

Before application, sponge (do not wipe) recipient surface free of blood; otherwise, blood may clot on surface layers while bleeding continues underneath clot. After application, avoid sponging treated areas so clot is not disturbed.

When used with an absorbable gelatin sponge, immerse sponge strips of the desired size in the solution and knead vigorously with moistened, gloved fingers to remove trapped air and facilitate saturation. Apply the saturated sponge to the bleeding area and hold in place with a cotton pledget or small gauze sponge until hemostasis occurs. Consult manufacturer's information for detailed instructions on use of absorbable gelatin sponge preparations.

Reconstitution

To prepare a solution containing 1000 units/mL of thrombin (bovine), transfer entire contents of the supplied diluent vial (5 or 20 mL) to a vial containing 5000 or 20,000 units, respectively, of lyophilized thrombin via a syringe or transfer needle. Consult manufacturer's instructions for appropriate use of the transfer device.

Use an appropriate volume of the 0.9% sodium chloride diluent to prepare other concentrations.

Dosage

Adults

Hemorrhage

Topical

Plastic surgery, dental extractions, skin grafting, other general uses: Solutions containing approximately 100 units/mL are frequently used.

Profuse bleeding (e.g., from cut surfaces of the liver or spleen): Solutions containing 1000 units/mL may be required.

Contraindications

• Known sensitivity to any ingredient in the formulation and/or to material of bovine origin.

Warnings/Precautions

Warnings

Effects on Hemostasis

Because of its hemostatic activity, thrombin should not be injected or otherwise allowed to enter large blood vessels; may result in extensive intravascular clotting and even death.

Abnormalities in hemostasis reported, ranging from asymptomatic alterations in coagulation test results (e.g., PT, PTT) to severe bleeding or thrombosis (rarely fatal); may be related to antibody formation. (See Antibody Formation under Cautions.)

Consult an expert in coagulation disorders if patient exhibits abnormal coagulation test results, bleeding, or thrombosis. Consider underlying immunologic mechanisms with any contemplated intervention.

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis with profound bradycardia and hypotension reported rarely.

Potential allergic reactions in patients sensitive to bovine materials.

Antibody Formation

Can stimulate antibody formation against bovine thrombin and/or bovine factor V (a potential contaminant in some bovine thrombin preparations). Such antibodies may cross-react with human factor V, potentially resulting in a factor V deficiency and hemorrhagic complications; paradoxical thrombosis also has occurred. (See Effects on Hemostasis under Cautions.) Antibodies may develop as early as 8 days after use and may persist for months to years following initial exposure. Not known whether highly purified preparations (i.e., containing no detectable levels of factor Va) are associated with reduced risk of immunogenicity.

Patients with evidence of anti-bovine thrombin antibodies should not be reexposed to the drug; increased likelihood of antibody formation with repeated application.

General Precautions

Concomitant Absorbable Gelatin Sponge

Consult prescribing information for absorbable gelatin sponge preparations when used concomitantly.

Specific Populations

Pregnancy

Category C.

Pediatric Use

Safety and efficacy not established.

General

• The concentration of thrombin solutions used depends on the severity of bleeding.

Administration

Topical Administration

Apply topically as a powder or solution; do not inject.

Prepare and administer solution according to manufacturer's recommendations. Use solution promptly upon removal from container.

Spray reconstituted solution directly onto bleeding surfaces (using a sterile syringe and spray tip, spray pump and actuator, or nasal delivery device) or apply with an absorbable gelatin sponge; do not leave solution in syringe as an intermediate step when preparing the spray delivery device.

Alternatively, flood surfaces with thrombin solution using a sterile syringe and small gauge needle. To avoid inadvertent intravascular administration, label syringes containing reconstituted thrombin (bovine) with a warning against IV injection and keep separate from parenteral preparations.

May apply as a dry powder; preferred method of application to oozing surfaces in some cases.

May use in conjunction with a bovine gelatin-based hemostatic matrix (e.g., FloSeal NT).

Before application, sponge (do not wipe) recipient surface free of blood; otherwise, blood may clot on surface layers while bleeding continues underneath clot. After application, avoid sponging treated areas so clot is not disturbed.

When used with an absorbable gelatin sponge, immerse sponge strips of the desired size in the solution and knead vigorously with moistened, gloved fingers to remove trapped air and facilitate saturation. Apply the saturated sponge to the bleeding area and hold in place with a cotton pledget or small gauze sponge until hemostasis occurs. Consult manufacturer's information for detailed instructions on use of absorbable gelatin sponge preparations.

Reconstitution

To prepare a solution containing 1000 units/mL of thrombin (bovine), transfer entire contents of the supplied diluent vial (5 or 20 mL) to a vial containing 5000 or 20,000 units, respectively, of lyophilized thrombin via a syringe or transfer needle. Consult manufacturer's instructions for appropriate use of the transfer device.

Use an appropriate volume of the 0.9% sodium chloride diluent to prepare other concentrations.

Dosage

Adults

Hemorrhage

Topical

Plastic surgery, dental extractions, skin grafting, other general uses: Solutions containing approximately 100 units/mL are frequently used.

Profuse bleeding (e.g., from cut surfaces of the liver or spleen): Solutions containing 1000 units/mL may be required.