Fibrin Sealant (Monograph)

Drug class: Basic Ointments and Protectants

Medically reviewed by Drugs.com on May 10, 2024. Written by ASHP.

Introduction

Fibrin sealant, a combination of 2 components (sealer protein concentrate [human] and thrombin [human]) derived from pooled human plasma, mimics the final stage of the blood coagulation cascade.

Uses for Fibrin Sealant

Adherence of Autologous Skin Grafts to Burn Wounds

Fibrin sealant is used to adhere autologous skin grafts to surgically prepared wound beds resulting from burns.

Safety and efficacy of fibrin sealant for adherence of split-thickness skin sheet grafts have been evaluated in a randomized, controlled, evaluator-blinded clinical study in 138 patients (mean age: about 31 years [13.8% were 6 years of age or younger, 15.2% were 7–18 years of age, 71% were older than 18 years of age]; 31.9% were female) with deep partial-thickness or full-thickness burns requiring excision and skin grafting. In the study population, the mean estimated total body surface area for all burn wounds was 13.6%; burn wound thickness was classified as full thickness in 76.8% of patients and as partial thickness in 23.2% of patients. In each patient, 2 comparable test sites were identified after burn wound excision; skin grafts were affixed at one site using fibrin sealant and at the other site using staples. The mean estimated total body surface area treated was 1.7% for both fibrin sealant and staple sites; the mean calculated dosing volume of fibrin sealant was 1.8 mL/100 cm² (range: 0.2–6 mL/100 cm²). The rate of complete wound closure (defined as total coverage of the wound with a contiguous layer of viable epithelium) for sites treated with fibrin sealant was considered to be at least comparable to those treated with staples. By day 28, complete wound closure was achieved in 43.3 or 37% of sites treated with fibrin sealant or staples, respectively.

Fibrin sealant is not indicated for hemostasis.

Related/similar drugs

thrombin topical, Evarrest, Recothrom, Artiss

Fibrin Sealant Dosage and Administration

Reconstitution and Administration

Fibrin sealant is commercially available as a kit (containing freeze-dried sealer protein concentrate [human], fibrinolysis inhibitor solution [synthetic], freeze-dried thrombin [human], and calcium chloride solution) and as a prefilled dual-chamber syringe (containing frozen sealer protein solution and thrombin solution). The manufacturer’s labeling should be consulted for information on the proper handling, storage, and preparation of fibrin sealant. Vials and prefilled syringes of fibrin sealant are for single use only; unused contents should be discarded.

The commercially available freeze-dried fibrin sealant (in the kit) must be prepared according to the manufacturer’s directions prior to administration by reconstituting the freeze-dried sealer protein concentrate with fibrinolysis inhibitor solution and by reconstituting thrombin with calcium chloride solution. The kit should not be exposed to temperatures exceeding 37°C. Separate syringes should be used for reconstituting sealer protein and thrombin solutions to prevent premature clotting. The resultant sealer protein solution and thrombin solution are combined using the Duploject Preparation and Application System (or an equivalent delivery device approved by the US Food and Drug Administration [FDA] for use with fibrin sealant). Following reconstitution, the product should not be refrigerated and must be used within 4 hours.

Commercially available frozen prefilled syringes containing fibrin sealant must be thawed according to the manufacturer’s directions prior to administration. Fibrin sealant in prefilled syringes should not be used unless completely thawed and warmed to liquid consistency. The frozen prefilled syringes should not be exposed to temperatures exceeding 37°C and should not be microwaved, refrigerated, or refrozen. The protective syringe cap should not be removed until use. The fibrin sealant should be applied according to the manufacturer’s directions using the Duo Set. After thawing, the product must be stored at 15–37°C and used within 12 hours after warming to 33–37°C or removal from original pouches.

Prepared fibrin sealant should be administered using the Easyspray and Spray Set (or an equivalent device approved by FDA for application of fibrin sealant). The surgically prepared wound surface should be as dry as possible before application of fibrin sealant. The aerosolized drug should be applied to the wound in a thin layer, using a painting motion from side to side to achieve a single thin application. Excessive clot thickness may reduce product efficacy and interfere with wound healing. The skin graft should be attached to the wound bed immediately after applying fibrin sealant, which will take approximately 60 seconds to polymerize; 0.9% sodium chloride should be applied on gloves to prevent adherence. The graft should be held in the desired position using gentle compression for at least 3 minutes to ensure that the fibrin sealant sets properly and adheres firmly to the surrounding tissue. The solidified fibrin sealant reaches its final strength approximately 2 hours after application. The cannulas included with the Duploject Preparation and Application System or Duo Set may be used for small wounds or for edges of a skin graft that did not adhere to the wound bed.

Sealer protein solutions and thrombin solutions can be denatured by alcohol, iodine, or heavy metal ions. If any of these substances have been used to clean the wound area, the area must be rinsed thoroughly and made as dry as possible prior to application of fibrin sealant. Iodine- or heavy metal-containing preparations (e.g., betadine) should not be used for disinfection of vial stoppers. Alcohol-based disinfectants should be allowed to evaporate before puncturing the stopper.

Dosage

Adherence of Autologous Skin Grafts to Burn Wounds

In adults and children 1 year of age or older, the required dosage of fibrin sealant depends on the size of the surface to be covered. Fibrin sealant package sizes of 2, 4, and 10 mL will cover areas of approximately 100, 200, and 500 cm², respectively.

Cautions for Fibrin Sealant

Contraindications

Known hypersensitivity to aprotinin (a component of the fibrinolysis inhibitor solution in the kit [see Description]).

Intravascular application. Administration directly into blood vessels may result in life-threatening thromboembolic events.

Warnings/Precautions

Warnings

Risk of Transmissible Agents in Plasma-derived Preparations

Because fibrin sealant is prepared from pooled human plasma, it may carry a risk of transmitting infectious agents (e.g., viruses) and, theoretically, the causative agent of Creutzfeldt-Jakob disease (CJD). The risk of transmission of infectious agents associated with fibrin sealant has been reduced by donor screening practices, testing for the presence of certain viral infections, and by inactivating and removing certain viruses. Vapor heat and chemical (solvent/detergent) treatment steps in the manufacturing of fibrin sealant have been shown to reduce substantially the viral infectious potential of the preparation. However, no method has been shown to be totally effective in removing the risk of viral infectivity from preparations derived from pooled human plasma and there is still a possibility of human viral transmission from these preparations. All infections thought possibly to have been transmitted by the use of fibrin sealant should be reported by the clinician to Baxter Healthcare Corporation at 866-888-2472.

Sensitivity Reactions

Hypersensitivity or allergic/anaphylactoid reactions may occur with the use of fibrin sealant. Such reactions may progress to severe anaphylaxis. The risk of such reactions may be increased if fibrin sealant is applied repeatedly over time or in the same setting or in patients who previously have received systemic aprotinin (see Description). Such reactions also may occur in patients receiving fibrin sealant for the first time or in patients who previously received and tolerated well treatment with fibrin sealant or systemic aprotinin.

If hypersensitivity reactions occur, administration of fibrin sealant should be discontinued; the already applied, polymerized product should be removed from the surgical field. Mild reactions may be managed with antihistamines; severe hypotensive reactions should be treated immediately using currently accepted treatment measures for shock.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether fibrin sealant is distributed into human milk. Caution is advised if the drug is administered in nursing women.

Pediatric Use

No substantial differences in safety and efficacy in pediatric patients (age: 1–16 years of age) relative to adults.

Geriatric Use

No experience to date with use of fibrin sealant in patients 65 years of age or older.

Common Adverse Effects

Adverse effects occurring in more than 1% of patients receiving fibrin sealant include skin graft failure and pruritus.

Drug Interactions

Drug interaction studies with fibrin sealant have not been performed to date.

Description

Fibrin sealant consists of 2 components (sealer protein [human] and thrombin [human]) derived from pooled human plasma. When combined, the 2 components mimic the final stage of the blood coagulation cascade. The active ingredient in sealer protein is fibrinogen; sealer protein is available as a freeze-dried powder (in a kit) for reconstitution with fibrinolysis inhibitor solution or as a frozen solution prefilled into one side of a dual-chambered syringe. Each mL of reconstituted or frozen sealer protein solution contains 96–125 mg of total protein, 67–106 mg of fibrinogen, and 2250–3750 kallikrein inactivator units (KIU) of fibrinolysis inhibitor; other ingredients include human albumin, trisodium citrate, histidine, niacinamide, polysorbate 80, and water for injection. The fibrinolysis inhibitor solution contains aprotinin, a polyvalent protease inhibitor that prevents premature degradation of fibrin and delays fibrinolysis. (See Cautions: Contraindications.) Thrombin, a highly specific protease that transforms the fibrinogen contained in sealer protein into fibrin, is available as a freeze-dried powder for reconstitution with calcium chloride solution (in the kit) or as a frozen liquid solution prefilled into one side of the dual-chambered syringe. Each mL of reconstituted or frozen thrombin solution contains 2.5–6.5 international units (IU) of thrombin and 36–44 µmol of calcium chloride; other ingredients include human albumin, sodium chloride, and water for injection.

Upon combination of sealer protein and thrombin, soluble fibrinogen is transformed into fibrin, which adheres to the burn wound surface and the skin graft to be affixed. The low thrombin concentration present in the combined product results in a 60-second period before polymerization occurs, providing time for the clinician to manipulate and position the skin graft on the surgically prepared wound bed. Fibrin sealant is applied only topically; systemic exposure or distribution to other organs and tissues is not expected.

Advice to Patients

Importance of advising patients of potential risk of infection from products derived from pooled human plasma.

Importance of patients informing clinicians if symptoms of parvovirus B19 infection (e.g., fever, drowsiness, chills, and rhinitis followed about 2 weeks later by rash and joint pain) develop.

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

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

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

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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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