Thrombin (Monograph)

Brand name: Thrombin-JMI
Drug class: Hemostatics
CAS number: 9002-04-4

Medically reviewed by Drugs.com on Jan 22, 2024. Written by ASHP.

Introduction

Hemostatic agent.^{100 b}

Uses for Thrombin

Hemorrhage

Aids hemostasis at accessible sites of oozing blood and minor bleeding from capillaries and small venules.¹⁰⁰ In various types of surgery, may be used in conjunction with an absorbable gelatin sponge.¹⁰⁰

Does not control arterial bleeding when used alone.^b

Thrombin Dosage and Administration

General

• The concentration of thrombin solutions used depends on the severity of bleeding.^{100 109 b}

Administration

Topical Administration

Apply topically as a powder or solution; do not inject.^{100 102}

Prepare and administer solution according to manufacturer's recommendations.¹⁰⁰ Use solution promptly upon removal from container.¹⁰⁰

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;¹⁰⁰ do not leave solution in syringe as an intermediate step when preparing the spray delivery device.¹⁰²

Alternatively, flood surfaces with thrombin solution using a sterile syringe and small gauge needle.¹⁰⁰ To avoid inadvertent intravascular administration, label syringes containing reconstituted thrombin (bovine) with a warning against IV injection and keep separate from parenteral preparations.¹⁰²

May apply as a dry powder; preferred method of application to oozing surfaces in some cases.^{100 102}

May use in conjunction with a bovine gelatin-based hemostatic matrix (e.g., FloSeal NT).¹⁰⁰

Before application, sponge (do not wipe) recipient surface free of blood; otherwise, blood may clot on surface layers while bleeding continues underneath clot.¹⁰⁰ After application, avoid sponging treated areas so clot is not disturbed.¹⁰⁰

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.¹⁰⁰ Apply the saturated sponge to the bleeding area and hold in place with a cotton pledget or small gauze sponge until hemostasis occurs.¹⁰⁰ Consult manufacturer's information for detailed instructions on use of absorbable gelatin sponge preparations.¹⁰⁰

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.¹⁰⁰ Consult manufacturer's instructions for appropriate use of the transfer device.¹⁰⁰

Use an appropriate volume of the 0.9% sodium chloride diluent to prepare other concentrations.¹⁰⁰

Dosage

Adults

Hemorrhage

Topical

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

Profuse bleeding (e.g., from cut surfaces of the liver or spleen): Solutions containing 1000 units/mL may be required.^{100 b}

Cautions for Thrombin

Contraindications

• Known sensitivity to any ingredient in the formulation and/or to material of bovine origin.¹⁰⁰

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.^{100 102}

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.^{100 103 105 106 108 109 110 111 112} (See Antibody Formation under Cautions.)

Consult an expert in coagulation disorders if patient exhibits abnormal coagulation test results, bleeding, or thrombosis.¹⁰⁰ Consider underlying immunologic mechanisms with any contemplated intervention.^{100 106}

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis with profound bradycardia and hypotension reported rarely.^{101 b}

Potential allergic reactions in patients sensitive to bovine materials.¹⁰⁰

Antibody Formation

Can stimulate antibody formation against bovine thrombin and/or bovine factor V (a potential contaminant in some bovine thrombin preparations).^{100 103 104 105 106 109 110 111 112} Such antibodies may cross-react with human factor V, potentially resulting in a factor V deficiency and hemorrhagic complications; paradoxical thrombosis also has occurred.^{100 103 105 106 107 109 111 112} (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.^{103 105 106 111} Not known whether highly purified preparations (i.e., containing no detectable levels of factor Va) are associated with reduced risk of immunogenicity.^{100 109}

Patients with evidence of anti-bovine thrombin antibodies should not be reexposed to the drug; increased likelihood of antibody formation with repeated application.^{100 103 104 105 106 107 109 111}

General Precautions

Concomitant Absorbable Gelatin Sponge

Consult prescribing information for absorbable gelatin sponge preparations when used concomitantly.¹⁰⁰

Specific Populations

Pregnancy

Category C.¹⁰⁰

Pediatric Use

Safety and efficacy not established.¹⁰⁰

Stability

Storage

Topical

Powder

2–25°C.¹⁰⁰ May refrigerate reconstituted solution at 2–8°C for up to 24 hours or store at room temperature for up to 8 hours.¹⁰⁰

Actions

• Causes clotting of whole blood or plasma without the addition of other substances.^{100 b} Affects hemostasis principally by converting fibrinogen to fibrin; several other mechanisms (e.g., stimulation of platelet release reaction, aggregation of platelets) may be involved.^{100 109 b}

• Rate of blood clotting depends on concentration of thrombin and fibrinogen.^{100 b}

• Does not clot blood when clotting defect is the rare absence of fibrinogen.¹⁰⁰

Advice to Patients

• Importance of informing clinician of allergy to bovine materials. (See Cautions.)¹⁰⁰

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹⁰⁰

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹⁰⁰

• Importance of informing patients of other important precautionary information.¹⁰⁰ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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