Thrombin

Pronunciation: THROM-bin
Class: Hematologic agent

Trade Names

Evithrom
- Solution, frozen, topical 800 to 1,200 units/mL (human origin)

Recothrom
- Powder for solution, lyophilized, topical 1,000 units/mL when reconstituted (recombinant)

Thrombi-Gel 10
- Pad, lyophilized, topical 1,000 units (bovine origin)

Thrombi-Gel 40
- Pad, lyophilized, topical 1,000 units (bovine origin)

Thrombi-Gel 100
- Pad, lyophilized, topical 20,000 units (bovine origin)

Thrombi-Pad 3×3
- Pad, lyophilized, topical 200 units (bovine origin)

Thrombin-JMI
- Powder for solution, lyophilized, topical 1,000 units/mL when reconstituted (bovine origin)

Pharmacology

Thrombin activates platelets and catalyzes the conversion of fibrinogen to fibrin, which are the steps that are essential for blood clot formation. The fibrin clot is stabilized by cross-linking that occurs as a result of activation of the patient's endogenous factor XIII, which requires the presence of calcium.

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Pharmacokinetics

Pharmacokinetic studies have not been performed.

Indications and Usage

Evithrom , Recothrom , Thrombin-JMI

As an aid to hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques is ineffective or impractical.

Thrombi-Gel , Thrombi-Pad

As a trauma dressing for temporary control of moderately to severely bleeding wounds and for the control of surface bleeding from vascular access sites and percutaneous catheters and tubes.

Contraindications

Evithrom

Individuals known to have anaphylactic or severe systemic reaction to human blood products; injection directly into the circulatory system; for the treatment of severe or brisk arterial bleeding.

Recothrom

Known hypersensitivity to thrombin, hamster proteins, or any component of the product; injection directly into the circulatory system; for the treatment of massive or brisk arterial bleeding.

Thrombi-Gel

Known hypersensitivity to any component of the product (including material of bovine origin); use in the closure of skin incisions.

Thrombi-Pad and Thrombin-JMI

Known sensitivity to any component of the product and/or material of bovine origin.

Dosage and Administration

Hemostasis

The amount of thrombin required will vary depending on the size and number of bleeding sites and the method of application.

Evithrom Adults and Children

Topical As an approximate guide, volumes up to 10 mL were used in clinical studies when human thrombin was used in conjunction with an absorbable gelatin sponge.

Thrombin-JMI Adults

Topical Where bleeding is profuse, as from abraded surfaces of liver or spleen, concentrations of 1,000 units/mL may be required. For general use in plastic surgery, dental extractions, skin grafting, etc, solutions containing approximately 100 units/mL are frequently used.

General Advice

  • For topical use only. Do not inject. Topically apply on the surface of bleeding tissue only.
  • The health care provider should determine the number of vials required to produce a sufficient volume of reconstituted product. See prescribing information for preparation instructions.
  • Inspect the package and contents for damage prior to use; do not use if the package has been damaged or opened.
  • The recipient surface should be sponged (not wiped) or suctioned free of blood before thrombin is applied. A spray may be used or the surface may be flooded using a sterile syringe and small gauge needle. The most effective hemostasis results occur when the thrombin mixes freely with the blood as soon as it reaches the surface. Sponging of the treated surfaces should be avoided to ensure that the clot remains securely in place.
  • Thrombin solution may be used with an absorbable gelatin sponge. Prepare thrombin solution to desired strength. Transfer solution from syringe to a sterile bowl or basin. Immerse sponge of the desired size in solution. Knead the sponge vigorously with moistened gloved fingers to remove trapped air, thereby facilitating saturation of the sponge. Remove the saturated sponge(s) and squeeze gently to remove excess solution. Apply saturated sponge to bleeding area in a single layer. Hold in place with a pledget of cotton or a small gauze sponge until hemostasis occurs.
  • Epistaxis kit: Insert the nasal drug delivery device into the naris and spray the solution onto the nasal mucosa by depressing the syringe plunger using mild or moderate pressure. If feasible, the bleeding site on the patient's nasal mucosa may be placed in a dependent position during administration. After administration, the device may be removed immediately or briefly held in the nasal passage.
  • Pad: Place the wetted pad directly over the source of the bleeding and apply adjunct manual compression until hemostasis is achieved. The Thrombi-Pad 3×3 pad may be left in place for up to 24 h. Upon removal, do not disrupt the clot by physical manipulation. If the pad adheres to the placement site, gently irrigate the pad with nonheparinized saline and carefully remove it.

Storage/Stability

Evithrom

Store frozen vials at −0.4°F or colder for up to 2 y. Unopened thawed vials can be stored at 36° to 46°F for up to 30 days or at room temperature for up to 24 h. Do not refreeze. Do not refrigerate after reaching room temperature. Discard unused product.

Recothrom

Store vials at 36° to 77°F. Reconstituted solutions may be stored for up to 24 h at 36° to 77°F. Discard reconstituted solution after 24 h. Discard unused product.

Thrombi-Gel , Thrombi-Pad

Store at 36° to 77°F in a cool, dry place. Discard Thrombi-Gel 3 h and Thrombi-Pad 1 h after preparation.

Thrombin-JMI

Store vials at 36° to 77°F. Solutions should be used promptly upon removal from the container. However, the solution may be refrigerated at 36° to 46°F for up to 24 h or stored at room temperature for up to 8 h following reconstitution. Discard unused contents.

Drug Interactions

None well documented.

Adverse Reactions

Cardiovascular

Cardiac adverse reaction (20%); thromboembolic adverse reaction (6%).

GI

Nausea and vomiting (40%); nausea (35%);

Lab Tests

Increased APTT, prolonged PT (5%); decreased lymphocytes, increased INR (3%); increased neutrophils (2%).

Miscellaneous

Incision-site complication (63%); procedural pain (34%); hypersensitivity (18%); other infection (15%); bleeding (13%); postoperative wound infection (11%); pruritus (2%); antibody formation.

Precautions

Warnings

The use of topical bovine thrombin has occasionally been associated with abnormalities in hemostasis ranging from asymptomatic alterations in laboratory determinations, such as PT and PTT, to severe bleeding or thrombosis, which rarely have been fatal. These hemostatic effects appear to be related to the formation of antibodies against bovine thrombin and/or factor V, which in some cases may cross-react with human factor V, potentially resulting in factor V deficiency. Repeated clinical applications of bovine thrombin increase the likelihood that antibodies against thrombin and/or factor V may be formed. Consultation with an expert in coagulation disorders is recommended if a patient exhibits abnormal coagulation laboratory values, abnormal bleeding, or abnormal thrombosis following the use of topical thrombin. Patients with antibodies to bovine thrombin should not be reexposed to these products.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established for Recothrom , Thrombi-Gel , Thrombi-Pad , or Thrombin-JMI .

Elderly

Greater sensitivity of some older individuals cannot be ruled out.

Hypersensitivity

In patients with known hypersensitivity to snake proteins, there may be a potential for an allergic reaction to Recothrom .

Administration

Thrombin must not be injected or otherwise allowed to enter large blood vessels; extensive intravascular clotting and even death may result. Do not use Thrombi-Pad 3×3 as a replacement for absorbable hemostats; the product contains nonabsorbable materials and is not intended to be left in the body. Thrombi-Gel should not used in the closure of skin incisions because it may interfere with the healing of skin edges.

Human plasma

Some of these products are prepared from human plasma; there is a risk of transmitting infectious agents (eg, viruses), including Creutzfeldt-Jakob disease.

Immunogenicity

Antibody formation may occur.

Infections

Do not use Thrombi-Gel or Thrombi-Pad in the presence of infection; use with caution in contaminated areas of the body.

Thrombosis

Potential risk of thrombosis if absorbed systemically.

Overdosage

Symptoms

None reported.

Patient Information

  • Advise patients to notify health care provider immediately if they experience the following symptoms: abdominal pain, chills, dark urine, drowsiness, fatigue, fever, joint pain, nausea, poor appetite, rash, runny nose, vomiting, and/or yellow complexion.

Copyright © 2009 Wolters Kluwer Health.

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