Thrombin

Class: Hemostatics
CAS Number: 9002-04-4
Brands: Thrombin-JMI

Warning(s)

  • Use of topical thrombin (bovine) can stimulate antibody formation against bovine thrombin and/or bovine factor V, potentially resulting in severe hemorrhagic or thrombotic complications; rarely fatal.100 103 104 105 106 107 109 110 111 112 (See Antibody Formation under Cautions.)

  • Consult expert in coagulation disorders if patient exhibits abnormal coagulation test results, bleeding, or thrombosis.100 Do not readminister drug to patients with evidence of anti-bovine thrombin antibodies.100 103 104 105 106 107 109 111

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

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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.

Thrombin (Bovine)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Powder

5000 units

Thrombin-JMI (with 0.9% sodium chloride diluent)

King

Thrombin-JMI (with 0.9% sodium chloride diluent; epistaxis kit also contains nasal delivery device and syringe)

King

20,000 units

Thrombin-JMI (with 0.9% sodium chloride diluent)

King

Thrombin-JMI (with 0.9% sodium chloride diluent; syringe spray kit also contains sterile syringe with transfer device and spray tip)

King

Thrombin-JMI (with 0.9% sodium chloride diluent; pump spray kit also contains spray pump and actuator)

King

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 1, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

100. King Pharmaceuticals, Inc. Thrombin-JMI (thrombin, topical USP) bovine origin prescribing information. Bristol, TN; 2007 Nov.

101. Rothenberg DM, Moy JN. Anaphylactic reaction to topical bovine thrombin. Anesthesiology. 1993; 78:779-82. [IDIS 316352] [PubMed 8096685]

102. Cohen MR, Smetzer JL. ISMP medical error report analysis: Danger of giving topical thrombin intravascularly. Hosp Pharm. 2007; 42:284-5.

103. Winterbottom N, Kuo JM, Nguyen K et al. Antigenic responses to bovine thrombin exposure during surgery: a prospective study of 309 patients. J Applied Research. 2002; 2:1–11.

104. Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Ferraris VA, Ferraris SP et al. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg. 2007; 83:S27-86. [PubMed 17462454]

105. Ortel TL, Mercer MC, Thames EH et al. Immunologic impact and clinical outcomes after surgical exposure to bovine thrombin. Ann Surg. 2001; 233:88-96. [PubMed 11141230]

106. Streiff MB, Ness PM. Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombin exposure. Transfusion. 2002; 42:18-26. [PubMed 11896308]

107. Doria C, Fischer CP, Wood CG et al. Phase 3, randomized, double-blind study of plasma-derived human thrombin versus bovine thrombin in achieving hemostasis in patients undergoing surgery. Curr Med Res Opin. 2008; 24:785-94. [PubMed 18241525]

108. Chapman WC, Singla N, Genyk Y et al. A phase 3, randomized, double-blind comparative study of the efficacy and safety of topical recombinant human thrombin and bovine thrombin in surgical hemostasis. J Am Coll Surg. 2007; 205:256-65. [PubMed 17660072]

109. Cheng CM, Meyer-Massetti C, Kayser SR. A review of three stand-alone topical thrombins for surgical hemostasis. Clin Ther. 2009; 31:32-41. [PubMed 19243705]

110. Clark J, Crean S, Reynolds MW. Topical bovine thrombin and adverse events: a review of the literature. Curr Med Res Opin. 2008; 24:2071-87. [PubMed 18549663]

111. Dorion RP, Hamati HF, Landis B et al. Risk and clinical significance of developing antibodies induced by topical thrombin preparations. Arch Pathol Lab Med. 1998; 122:887-94. [PubMed 9786349]

112. Lundblad RL, Bradshaw RA, Gabriel D et al. A review of the therapeutic uses of thrombin. Thromb Haemost. 2004; 91:851-60. [PubMed 15116244]

b. AHFS Drug Information 2004. McEvoy GK, ed. Heparin. Bethesda, MD: American Society of Health-System Pharmacists; 2004: 1454-5.

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