Fibrin Sealants

Definition
Purpose
Description
Preparation
Normal results

Definition

Fibrin sealants are a type of surgical tissue adhesive derived from human and animal blood products. The ingredients in these sealants interact during application to form a stable clot composed of a blood protein called fibrin. Fibrin sealants are also called fibrin glues. They have been used in Japan and Western Europe since the 1980s, but were not approved for use in the United States until 1998 due to the Food and Drug Administration’s (FDA) concerns about virus contamination. As of 2007, all fibrin sealants used in the United States are made from blood plasma taken from carefully screened donors and rigorously tested to eliminate hepatitis viruses, HIV-1, and parvovirus.

Purpose

Originally developed during World War II to stop bleeding from battle injuries, fibrin sealants are presently used during surgery for several different purposes, including:

• to control bleeding in the area where the surgeon is operating
• to speed wound healing
• to seal off hollow body organs or cover holes made by standard sutures
• to provide slow-release delivery of medications to tissues exposed during surgery
• to reduce blood loss from skin grafting during operations to treat severe burns
• to deliver localized doses of antibiotics to lower the risk of infection after surgery

Fibrin sealants have several advantages over older methods of hemostasis (stopping bleeding): they speed up the formation of a stable clot; they can be applied to very small blood vessels and to areas that are difficult to reach with conventional sutures; they reduce the amount of blood lost during surgery; they lower the risk of postoperative inflammation or infection; and they are conveniently absorbed by the body during the healing process. They are particularly useful to minimize blood loss during surgery for severe burns, for minimally invasive procedures, and for treating patients with blood clotting disorders. Fibrin sealants are being replaced for some specialized purposes by newer wound adhesives known as cyanoacrylates. Fibrin sealants have a major advantage over cyanoa-crylates, however, in that they are less likely to cause allergic reactions or inflammation that slows wound healing.

Description

All fibrin sealants in use as of 2007 have two major ingredients: purified fibrinogen (a protein) and purified thrombin (an enzyme) derived from human or bovine (cattle) blood. Many sealants have two additional ingredients: human blood factor XIII and a substance called aprotinin, which is derived from cows’ lungs. Factor XIII is a compound that strengthens blood clots by forming cross-links between strands of fibrin. Aprotinin is a protein that inhibits the enzymes that break down blood clots.

Preparation

The preparation and application of fibrin sealants are somewhat complicated. The thrombin and fibrinogen are freeze-dried and packaged in vials that must be warmed before use. The two ingredients are then dissolved in separate amounts of water. Next, the thrombin and fibrinogen solutions are loaded into a double-barreled syringe that allows them to mix and combine as they are sprayed on the incision. Pieces of surgical gauze or fleece may be moistened with the sealant solutions to cover large incisions or stop heavy bleeding.

KEY TERMS

Aprotinin— A protein derived from cows’ lungs included in some fibrin sealants to prevent the fibrin clot from dissolving.

Coagulation cascade— The process of blood clotting. The cascade itself is a series of chemical reactions involving blood proteins and enzymes that occurs wherever there is a break in a blood vessel. The end product of the cascade is a protein called fibrin.

Collagen— A fibrous protein found in the skin and other connective tissues of mammals. It is used to make patches coated with fibrinogen and thrombin as a wound sealant.

Factor XIII— A substance found in blood that forms cross-links between strands of fibrin during the process of blood coagulation. Factor XIII is an ingredient in some types of fibrin sealants. It is also known as fibrin stabilizing factor.

Fibrin— A blood protein formed as the end result of the coagulation cascade. Fibrin is formed from fibrinogen when it interacts with thrombin.

Fibrinogen— A blood protein made in the liver that is broken up into shorter molecules by the action of thrombin to form fibrin.

Hemostasis— Stopping bleeding from a wound or incision. Fibrin sealants are used to speed up hemostasis.

Plasma— The liquid part of blood. Plasma is a clear pale yellow fluid composed primarily of water and dissolved minerals.

Thrombin— An enzyme found in blood plasma that helps to convert fibrinogen into fibrin.

Fibrin sealants can also be applied in the form of a patch made from collagen, a protein found in the connective tissues of humans and other mammals. The collagen is coated with fibrinogen and thrombin to make a ready-to-use rapid-acting wound sealant. The coated patches are used in neurosurgery as well as cardiovascular, liver, and kidney surgery.

As the thrombin and fibrinogen solutions combine, a clot develops in the same way that it would form during normal blood clotting through a series of chemical reactions known as the coagulation cascade. At the end of the cascade, the thrombin breaks up the fibrinogen molecules into smaller segments of a second blood protein called fibrin. The fibrin molecules

arrange themselves into strands that are then cross-linked by a blood factor known as Factor XIII to form a lattice or net-like pattern that stabilizes the clot.

Fibrin sealants are undergoing rapid refinement as the result of recent advances in tissue adhesives in general. In 1997, the Tissue Adhesive Center (TAC) was founded at University of Virginia Health Sciences Center in order to develop and test new fibrin sealants and other surgical glues. As of 2007, the TAC has been reorganized as a specialty center within the university’s Surgical Therapeutic Advancement Center (STAC). Recent developments include a delivery system that forms a fibrin sealant from the patient’s own blood within a 30-minute cycle, and uses a spray pen rather than a double-barreled syringe for applying the sealant. The use of the patient’s own blood lowers the risk of allergic reactions to blood products derived from animal or donated blood.

Normal results

Reports that have been published between 2003 and 2007 indicate that fibrin sealants are a safe and highly effective form of surgical adhesive. A survey done in 2000 at the University of Virginia hospital found that over 90% of the surgeons who had tried fibrin sealants were pleased with the results. Several American studies have reported that fibrin sealants have improved surgical outcomes significantly by shortening the time required for operations; lowering the rate of infections and other complications; minimizing blood loss during surgery; and reducing the amount of scar tissue formed over incisions. German researchers have found that fibrin sealants containing Factor XIII generally give better results than those that do not.

Resources

BOOKS

Colman, Robert W., et al., eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 5th ed. Philadelphia: Lippincott Williams and Wilkins, 2006.

PERIODICALS

Albala, D.M. “Fibrin Sealants in Clinical Practice.” Cardiovascular Surgery 11 (August 2003): Supply 1, 5–11.

Dodd, R. A., R. Cornwell, N. E. Holm, et al. “The Vivostat Application System: A Comparison with Conventional Fibrin Sealant Application Systems.” Technology and Health Care 10 (2002): 401–411.

Erdogan, D., and T. M. van Gulik. “Evolution of Fibrinogen-Coated Collagen Patch for Use as a Topical Hemostatic Agent: A Review.” Journal of Biomedical Materials Research, Part B, Applied Biomaterials, September 5, 2007 [E-publication ahead of print].

Fortelny, R. H., A. H. Petter-Puchner, N. Walder, et al. “Cyanoacrylate Tissue Sealant Impairs Tissue Integration of Macroporous Mesh in Experimental Hernia Repair.” Surgical Endoscopy 21 (October 2007): 1781–1785.

Foster, K. “The Use of Fibrin Sealant in Burn Operations.” Surgery 142 (October 2007): 4 Suppl, S50–S54.

Tredwell, S., J. K. Jackson, D. Hamilton, et al. “Use of Fibrin Sealants for the Localized, Controlled Release of Cefazolin.” Canadian Journal of Surgery 49 (October 2006): 347–352.

ORGANIZATIONS

Center for Biologics Evaluation and Research (CBER), U.S. Food and Drug Administration (FDA). 1401 Rockville Pike, Rockville, MD 20852-1448. (800) 835-4700 or (301) 827-1800. http://www.fda.gov/cber (accessed March 22, 2008).

Tissue Adhesive Center, Surgical Therapeutic Advancement Center. P. O. Box 801370, Charlottesville, VA 22908. (434) 243-0315. http://www.healthsystem.virginia.edu/internet/stac/overview/home.cfm (accessed March 22, 2008).

OTHER

Smith, Andrew. “Use of Surgical Glue Takes Hold at Temple.” Temple Times, May 18, 2000 [cited February 18, 2003]. http://www.temple.edu/temple_times_archives/2000/5-18-00/glue.html (accessed March 22, 2008).

Rebecca Frey, PhD

Fibroid surgery seeMyomectomy