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 2003, 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:
to control bleeding in the area where the surgeon is operating
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
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 for minimally invasive procedures and for treating patients with blood clotting disorders. Fibrin sealants are, however, being replaced for some specialized purposes by newer wound adhesives known as cyanoacrylates.
Description
All fibrin sealants in use as of 2003 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.
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 was founded at the University of Virginia Health Sciences Center in order to develop and test new fibrin sealants and other surgical glues. 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 spraypen 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 2001 and 2003 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.
"Hemostasis and Coagulation Disorders." Section 11, Chapter 131, The Merck Manual of Diagnosis and Therapy. Ed. Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 1999-2001.
PERIODICALS
Dickneite, G., H. J. Metzner, M. Kroez, et al. "The Importance of Factor XIII as a Component of Fibrin Sealants." Journal of Surgical Research 107 (October 2002): 186-195.
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.
Jackson, M. R. "Fibrin Sealants in Surgical Practice: An Overview." American Journal of Surgery 182 (August 2001) (2 Suppl): 1S-7S.
Mankad, P. S., and M. Codispoti. "The Role of Fibrin Sealants in Hemostasis." American Journal of Surgery 182 (August 2001) (2 Suppl): 21S-28S.
Morikawa, T. "Tissue Sealing." American Journal of Surgery 182 (August 2001) (2 Suppl): 29S-35S.
ORGANIZATIONS
Center for Biologics Evaluation and Research (CBER), U.S. Food and Drug Administration (FDA). 1401 Rockville Pike, Rockville, MD 20852-1448. (800) 835-4709 or (301) 827-1800. <www.fda.gov/cber>.
Tissue Adhesive Center. University of Virginia Health Sciences Center, MR4 Building, Room 3122, Charlottesville, VA 22908. (434) 243-0315. <www.hsc.virginia.edu/tac>.
OTHER
Food and Drug Administration (FDA) Talk Paper T98-22. NewFibrin Sealant Approved to Help Control Bleeding inSurgery. Rockville, MD: U. S. Department of Health and Human Services, May 1, 1998.
