- Arthur J Silvergleid, MD
Arthur J Silvergleid, MD
- Section Editor — Transfusion Medicine
- Affiliate Associate Professor, Department of Pathology and Cell Biology
- University of South Florida, College of Medicine
- Medical Director, OneBlood, Inc.
- Elizabeth Peralta, MD
Elizabeth Peralta, MD
- Clinical Associate Professor
- Southern Illinois University School of Medicine
- Section Editors
- Steven Kleinman, MD
Steven Kleinman, MD
- Section Editor — Transfusion Medicine
- Clinical Professor of Pathology
- University of British Columbia, Vancouver
- Hilary Sanfey, MD
Hilary Sanfey, MD
- Section Editor — General Surgical Principles; Quality and Safety
- Professor of Surgery
- SIU School of Medicine
Fibrin sealant, or fibrin "glue," is a unique surgical hemostatic/sealant/adhesive material that is being used with increasing frequency in a variety of surgical situations. In practice, it is a two-component system in which a solution of concentrated fibrinogen and factor XIII are combined with a solution of thrombin and calcium to form a coagulum, simulating the final stage of the clotting cascade. Once the thrombin/calcium is combined with the fibrinogen/factor XIII, a fibrin clot forms in seconds, or somewhat slower if a more dilute form of thrombin is used. In some preparations, or in selected indications, an antifibrinolytic agent is included, presumably to prevent lysis of the clot [1,2]. In another preparation, chromatographic filtering techniques are used to reduce the amounts of plasminogen in the product, eliminating the need for any antifibrinolytic.
Commercially prepared fibrin sealants, including Tisseel, Beriplast, and Biocol have been used extensively in Europe for over 30 years. During much of this time, these products were not commercially available in the United States due to the reluctance of the Food and Drug Administration (FDA) to approve fibrinogen prepared from pooled human plasma, given the previously demonstrated increased risk of hepatitis transmission . Instead, cryoprecipitate, prepared from a single (autologous or allogeneic) donor, most often served as the fibrinogen source in the United States. However, in 1998, the FDA approved the first commercial fibrin sealant, Tisseel.
The use of fibrin sealant will be discussed here. Reviews of other agents used primarily for the purpose of reducing bleeding by causing blood to clot, sealing vessels, or gluing tissues are discussed separately (table 1) [4,5]. (See "Overview of topical hemostatic agents and tissues adhesives used in surgery".)
The search for the perfect operative sealant began in the first decade of the 20th century. By the 1940s, fibrinogen and thrombin were combined in operative settings. When Cohn fractionation led to the ability to generate highly concentrated fibrinogen preparations (in the 1960s), fibrin sealants were used to promote wound healing, skin grafting, and dural sealing; to provide hemostasis in microvascular surgery and parenchymal injury; and to serve as a matrix for bony chips and fragments in the repair of bone defects .
Much of the literature generated during the past 30 years has come from Europe, but later studies have also been performed in the United States as well as Asia. Although many early studies were anecdotal or lacking a reasonable control group, it appeared that fibrin sealant systems were effective for controlling slowly bleeding foci, diffuse oozing, bleeding from needle puncture sites, lymphatic leaks, serous fluid collections, and diffuse parenchymal organ hemorrhage [7,8].
- Kram HB, Nathan RC, Mackabee JR, et al. Clinical use of nonautologous fibrin glue. Am Surg 1988; 54:570.
- Harris DM, Siedentop KH, Ham KR, Sanchez B. Autologous fibrin tissue adhesive biodegration and systemic effects. Laryngoscope 1987; 97:1141.
- Bove JR. Fibrinogen--is the benefit worth the risk? Transfusion 1978; 18:129.
- Spotnitz WD, Burks S. Hemostats, sealants, and adhesives: components of the surgical toolbox. Transfusion 2008; 48:1502.
- Achneck HE, Sileshi B, Jamiolkowski RM, et al. A comprehensive review of topical hemostatic agents: efficacy and recommendations for use. Ann Surg 2010; 251:217.
- Alving BM, Weinstein MJ, Finlayson JS, et al. Fibrin sealant: summary of a conference on characteristics and clinical uses. Transfusion 1995; 35:783.
- Gibble JW, Ness PM. Fibrin glue: the perfect operative sealant? Transfusion 1990; 30:741.
- Radosevich M, Goubran HI, Burnouf T. Fibrin sealant: scientific rationale, production methods, properties, and current clinical use. Vox Sang 1997; 72:133.
- Matthew TL, Spotnitz WD, Kron IL, et al. Four years' experience with fibrin sealant in thoracic and cardiovascular surgery. Ann Thorac Surg 1990; 50:40.
- Ochsner MG, Maniscalco-Theberge ME, Champion HR. Fibrin glue as a hemostatic agent in hepatic and splenic trauma. J Trauma 1990; 30:884.
- Rakocz M, Mazar A, Varon D, et al. Dental extractions in patients with bleeding disorders. The use of fibrin glue. Oral Surg Oral Med Oral Pathol 1993; 75:280.
- Nervi C, Gamelli RL, Greenhalgh DG, et al. A multicenter clinical trial to evaluate the topical hemostatic efficacy of fibrin sealant in burn patients. J Burn Care Rehabil 2001; 22:99.
- Atkinson JB, Gomperts ED, Kang R, et al. Prospective, randomized evaluation of the efficacy of fibrin sealant as a topical hemostatic agent at the cannulation site in neonates undergoing extracorporeal membrane oxygenation. Am J Surg 1997; 173:479.
- Wang GJ, Goldthwaite CA Jr, Burks S, et al. Fibrin sealant reduces perioperative blood loss in total hip replacement. J Long Term Eff Med Implants 2003; 13:399.
- Schenk WG 3rd, Burks SG, Gagne PJ, et al. Fibrin sealant improves hemostasis in peripheral vascular surgery: a randomized prospective trial. Ann Surg 2003; 237:871.
- Chalmers RT, Darling Iii RC, Wingard JT, et al. Randomized clinical trial of tranexamic acid-free fibrin sealant during vascular surgical procedures. Br J Surg 2010; 97:1784.
- Saha SP, Muluk S, Schenk W 3rd, et al. Use of fibrin sealant as a hemostatic agent in expanded polytetrafluoroethylene graft placement surgery. Ann Vasc Surg 2011; 25:813.
- Vaiman M, Eviatar E, Segal S. Effectiveness of second-generation fibrin glue in endonasal operations. Otolaryngol Head Neck Surg 2002; 126:388.
- Tisseel [package insert]. Deerfield, IL: Baxter International Inc; 2012.
- Cain JE Jr, Dryer RF, Barton BR. Evaluation of dural closure techniques. Suture methods, fibrin adhesive sealant, and cyanoacrylate polymer. Spine (Phila Pa 1976) 1988; 13:720.
- Silberstein LE, Williams LJ, Hughlett MA, et al. An autologous fibrinogen-based adhesive for use in otologic surgery. Transfusion 1988; 28:319.
- Stuart JD, Kenney JG, Lettieri J, et al. Application of single-donor fibrin glue to burns. J Burn Care Rehabil 1988; 9:619.
- Foster K, Greenhalgh D, Gamelli RL, et al. Efficacy and safety of a fibrin sealant for adherence of autologous skin grafts to burn wounds: results of a phase 3 clinical study. J Burn Care Res 2008; 29:293.
- Hester TR Jr, Shire JR, Nguyen DB, et al. Randomized, controlled, phase 3 study to evaluate the safety and efficacy of fibrin sealant VH S/D 4 s-apr (Artiss) to improve tissue adherence in subjects undergoing rhytidectomy. Aesthet Surg J 2013; 33:487.
- Kram HB, Bansal M, Timberlake O, Shoemaker WC. Antibacterial effects of fibrin glue-antibiotic mixtures. J Surg Res 1991; 50:175.
- Kawasaki H, Shimizu T, Takakura K, Umezawa Y. [Pharmacodynamic study of mitomycin C mixed with fibrin glue for treatment of malignant brain tumors]. No Shinkei Geka 1994; 22:819.
- Burnouf-Radosevich M, Burnouf T, Huart JJ. Biochemical and physical properties of a solvent-detergent-treated fibrin glue. Vox Sang 1990; 58:77.
- Artiss [package insert]. Deerfield, IL: Baxter International Inc; 2011
- Bänninger H, Hardegger T, Tobler A, et al. Fibrin glue in surgery: frequent development of inhibitors of bovine thrombin and human factor V. Br J Haematol 1993; 85:528.
- Zehnder JL, Leung LL. Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin. Blood 1990; 76:2011.
- Streiff MB, Ness PM. Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombin exposure. Transfusion 2002; 42:18.
- Lundblad RL, Bradshaw RA, Gabriel D, et al. A review of the therapeutic uses of thrombin. Thromb Haemost 2004; 91:851.
- Ortel TL, Mercer MC, Thames EH, et al. Immunologic impact and clinical outcomes after surgical exposure to bovine thrombin. Ann Surg 2001; 233:88.
- Randleman CD Jr, Singla NK, Renkens KL, et al. Persistence of antibodies to the topical hemostat bovine thrombin. J Am Coll Surg 2010; 211:798.
- Chapman WC, Lockstadt H, Singla N, et al. Phase 2, randomized, double-blind, placebo-controlled, multicenter clinical evaluation of recombinant human thrombin in multiple surgical indications. J Thromb Haemost 2006; 4:2083.
- Ballard JL, Weaver FA, Singla NK, et al. Safety and immunogenicity observations pooled from eight clinical trials of recombinant human thrombin. J Am Coll Surg 2010; 210:199.
- Hoffman M, Jenner P. Variability in the fibrinogen and von Willebrand factor content of cryoprecipitate. Implications for reducing donor exposure. Am J Clin Pathol 1990; 93:694.
- Tamaki T, Aoki N. Cross-linking of alpha 2-plasmin inhibitor to fibrin catalyzed by activated fibrin-stabilizing factor. J Biol Chem 1982; 257:14767.
- Reiss RF, Oz MC. Autologous fibrin glue: production and clinical use. Transfus Med Rev 1996; 10:85.
- Oz MC, Jeevanandam V, Smith CR, et al. Autologous fibrin glue from intraoperatively collected platelet-rich plasma. Ann Thorac Surg 1992; 53:530.
- Quigley RL, Perkins JA, Gottner RJ, et al. Intraoperative procurement of autologous fibrin glue. Ann Thorac Surg 1993; 56:387.
- Vitagel [package insert]. Malvern, PA: Orthovita; 2006.
- Chapman WC, Clavien PA, Fung J, et al. Effective control of hepatic bleeding with a novel collagen-based composite combined with autologous plasma: results of a randomized controlled trial. Arch Surg 2000; 135:1200.
- Sherman R, Chapman WC, Hannon G, Block JE. Control of bone bleeding at the sternum and iliac crest donor sites using a collagen-based composite combined with autologous plasma: results of a randomized controlled trial. Orthopedics 2001; 24:137.
- Basu S, Marini CP, Bauman FG, et al. Comparative study of biological glues: cryoprecipitate glue, two-component fibrin sealant, and "French" glue. Ann Thorac Surg 1995; 60:1255.
- Soffer E, Ouhayoun JP, Anagnostou F. Fibrin sealants and platelet preparations in bone and periodontal healing. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003; 95:521.
- Liu L, Hartwig D, Harloff S, et al. Corneal epitheliotrophic capacity of three different blood-derived preparations. Invest Ophthalmol Vis Sci 2006; 47:2438.
- Sum R, Hager S, Pietramaggiori G, et al. Wound-healing properties of trehalose-stabilized freeze-dried outdated platelets. Transfusion 2007; 47:672.
- Spotnitz WD. Fibrin Sealant: The Only Approved Hemostat, Sealant, and Adhesive-a Laboratory and Clinical Perspective. ISRN Surg 2014; 2014:203943.
- Milde LN. An anaphylactic reaction to fibrin glue. Anesth Analg 1989; 69:684.
- Kawamura M, Sawafuji M, Watanabe M, et al. Frequency of transmission of human parvovirus B19 infection by fibrin sealant used during thoracic surgery. Ann Thorac Surg 2002; 73:1098.
- Dubrow T, Schwartz RJ, McKissock J, Wilson SE. Effect of aerosolized fibrin solution on intraperitoneal contamination. Arch Surg 1991; 126:80.
- Narakas A. The use of fibrin glue in repair of peripheral nerves. Orthop Clin North Am 1988; 19:187.
- Olsen PS, Hjelms E. Intravascular air after fibrin sealing by spray gun in cardiovascular surgery. Eur J Cardiothorac Surg 1989; 3:376.
- Umegaki T, Nishi K, Murao K, et al. [Lethal air embolism after spray of tissue adhesive-fibrinogen and factor XIII aerosol during laparoscopic partial nephrectomy]. Masui 2007; 56:1203.
- Ebner FM, Paul A, Peters J, Hartmann M. Venous air embolism and intracardiac thrombus after pressurized fibrin glue during liver surgery. Br J Anaesth 2011; 106:180.
- Felema GG, Bryskin RB, Heger IM, Saswata R. Venous air embolism from Tisseel use during endoscopic cranial vault remodeling for craniosynostosis repair: a case report. Paediatr Anaesth 2013; 23:754.
- CLINICAL APPLICATIONS
- COMPONENTS OF COMMERCIAL AND ALTERNATIVE PREPARATIONS
- - Source of thrombin
- Other coagulation factors
- Cryoprecipitate preparations
- Platelet derived products
- TECHNICAL CONSIDERATIONS
- ADVERSE REACTIONS
- Bleeding diathesis
- Transmission of disease
- Interference with tissue repair
- Air/gas embolism