Current applications of fibrin sealant in urologic surgery

REVIEW ARTICLE   Current applications of fibrin sealant in urologic surgery     L. Andrew Evans; Allen F. Morey Urology Service; Brooke Army Medical Center; Fort Sam Houston; Texas, USA Correspondence     ABSTRACT Biosurgical preparations designed to promote surgical hemostasis and tissue adhesion are being increasingly employed across all surgical disciplines. Fibrin sealant is the most widely studied and utilized biosurgical adjunct in urology. Complex reconstructive, oncologic, and laparoscopic genitourinary procedures are those most appropriate for sealant use. This article details the diverse urologic applications of fibrin sealant in the management of genitourinary injuries, surgery, and complications. Key words: fibrin sealant; urology; hemostasis; complications; surgery; biologics     INTRODUCTION Although most applications are off-label, tissue sealants and hemostatic agents are being increasingly employed across all surgical disciplines. Biosurgical compounds can serve as adjuncts to primary surgical therapy or may assist in managing or preventing surgical complications. In urology, hemostatic agents and tissue sealants are finding increasing roles in managing traumatic and iatrogenic urologic injuries and promoting optimal wound healing. Among the variety of hemostatic products now available in the United States (Table-1), fibrin sealant is the most widely utilized biosurgical agent in urologic surgery. This article details the diverse urologic applications of fibrin sealant for hemostasis, tissue adhesion, and urinary tract sealing.   FIBRIN SEALANT Development Mixtures of coagulation factors have been used in surgery for almost a century, dating back to the use of a fibrin emulsion by Bergel in 1909 to promote wound healing (1). Purified thrombin became available in 1938, and was first combined with fibrinogen in 1944 to enhance adhesion of skin grafts to burned soldiers (2). Although commercial fibrin sealant has been widely used in Europe since the 1970’s, concerns about possible viral transmission limited sealant use in the United States until recently. In 1998, Tisseel® (Baxter Healthcare, Deerfield, Illinois) became the first fibrin sealant approved by the Food and Drug Administration (FDA) for use in the United States. Although the three FDA approved indications for fibrin sealant are reoperative cardiac surgery, colon anastomosis, and treatment of splenic injury, fibrin sealants have been successfully employed in countless numbers of non-urologic surgical applications, including liver laceration, hepatic resection, bowel and vascular anastomoses, enterocutaneous and anorectal fistulae closure, cardiothoracic surgery, and neurosurgery. A review in 2002 by Shekarriz & Stoller (3) was the first major contemporary urological publication addressing the use of fibrin sealant in urologic surgery, and an increasing number of urological sealant applications have followed. Composition Fibrin sealant contains 2 major components (thrombin and highly concentrated fibrinogen) which replicate and augment the final stage of the coagulation cascade—the cleavage of fibrinogen into fibrin by the action of thrombin—when mixed together. It is important to note that the fibrinogen concentration of sealant is supraphysiologic, 15 to 25 times higher than that of circulating plasma. The resultant clot tends to form more rapidly and more reliably than normal. Other key components of fibrin sealant are Factor XIII, which covalently crosslinks the fibrin polymer to produce an insoluble fibrin coagulum, and an antifibrinolytic agent which inhibits fibrinolysis thus preserving the stable fibrin clot (Figure-1). Tisseel® (Baxter Healthcare, Deerfield, Illinois) and Crosseal® (Omrix Biopharmaceuticals, Ltd, Israel) are the two fibrin sealants currently marketed in the United States. Tisseel® contains bovine aprotinin as its antifibrinolytic agent. Aprotinin is a serine protease inhibitor derived from bovine lung that works to limit fibrinolysis by inhibiting plasmin, kallikrein, and trypsin. Crosseal utilizes only human-derived proteins by including tranexamic acid as its antifibrinolytic agent instead of bovine aprotinin. Tranexamic acid is a synthetic analogue of the amino acid lysine and competes for lysine binding sites on plasminogen and plasmin, preventing binding to fibrin and inhibiting fibrinolysis (4). Safety All approved fibrin sealant preparations utilize a combination of donor screening, serum testing and retesting after 90 days storage, and a two-step vapor heating process to ensure viral safety (5,6). These steps are highly effective in ensuring viral safety and, to our knowledge, there are in 2005 still no reported transmissions of blood-borne viral pathogens associated with the use of FDA approved fibrin sealants (5). One parvovirus B19 transmission involving a non-FDA approved fibrin sealant was reported from Japan, but most adults have preexisting antibodies to this virus and the infection is usually a self-limited diarrhea (7). Delivery Methods Fibrin sealants are administered using a dual-chamber delivery system in which one chamber containing fibrinogen and factor XIII is admixed with the other chamber containing thrombin directly at the site of application using a “Y” adaptor, allowing an immediate conversion of fibrinogen to fibrin as the solutions exit the syringe. Dual lumen catheters ensure smooth, rapid sealant delivery, and a variety of specialized catheters and cannulae are available for endoscopic, laparoscopic, and open surgical application. We have also successfully used a dual lumen peripherally inserted central catheter (PICC) line for percutaneous transrenal application (8). Polymerization into the biocompatible fibrin clot is completed within 3 minutes (9), and the clot is gradually broken down and removed from the site by macrophages within 2-4 weeks, eventually becoming histopathologically invisible, without fibrosis or foreign-body reaction (10).   UROLOGICAL APPLICATIONS Commercial fibrin sealant is employed for three major reasons in urologic surgery - as a hemostatic agent, a urinary tract sealant, and/or a tissue adhesive. A list of the most common urological applications is presented in Table-2. Fibrin sealant’s unique properties as a hemostatic agent, urinary tract sealant, and tissue adhesive make it an effective adjunct for managing complex urologic injury and promoting wound healing in the genitourinary tract.   Hemostasis Partial Nephrectomy Fibrin sealant has been used since 1979 in open partial nephrectomy (11). The recent advent of minimally invasive techniques for nephron sparing surgery has resulted in widespread fibrin sealant use during laparoscopic partial nephrectomy today (12-15). A recent survey of 193 members of the World Congress of Endourology discovered 68% of surgeons routinely utilized fibrin sealant to assist with hem (...truncated)