Clinical use of topical thrombin as a surgical hemostat

When surgical ligation of bleeding fails, or is not possible, surgeons rely on a number of hemostatic aids, including thrombin. This review discusses the history, pharmacology and clinical application of thrombin as a surgical hemostat. The initial thrombin was bovine in origin, but its use has been complicated by the formation of antibodies that cross react with human coagulation factors. This has been associated with life threatening bleeding and in some circumstances anaphylaxis and death. Human thrombin, isolated from pooled plasma of donors, has been developed in an effort to minimize these risks, but its downside is the potential of transmitting blood-borne pathogens and limited availability. Recently a recombinant thrombin has been developed and approved for use by the FDA. It has the advantage of being minimally antigenic and devoid of the risk if viral transmission. Thrombin is often used in conjunction with other hemostatic aids, including absorbable agents (like gelfoam, collagen, and cellulose), and with fibrinogen in fibrin glues. The last part of this review will discuss these agents in detail, and review their clinical applications.

[1]  A. Tobler,et al.  Fibrin glue in surgery: frequent development of inhibitors of bovine thrombin and human factor V , 1993, British journal of haematology.

[2]  W. Stummer,et al.  The use of local agents: Surgicel and Surgifoam. , 2005 .

[3]  K. Mann,et al.  Isolation and characterization of an acquired antithrombin antibody. , 1990, Blood.

[4]  S. Canonico The use of human fibrin glue in the surgical operations. , 2003, Acta bio-medica : Atenei Parmensis.

[5]  A. Gheissari,et al.  A polymeric sealant inhibits anastomotic suture hole bleeding more rapidly than gelfoam/thrombin: results of a randomized controlled trial. , 2002, Archives of surgery.

[6]  L. Taylor,et al.  Prospective randomized multicenter trial of fibrin sealant versus thrombin-soaked gelatin sponge for suture- or needle-hole bleeding from polytetrafluoroethylene femoral artery grafts. , 2003, Journal of vascular surgery.

[7]  T. Ortel,et al.  Antibodies to topical bovine thrombin correlate with access thrombosis. , 2000, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[8]  M. Streiff,et al.  Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombin exposure , 2002, Transfusion.

[9]  L. Niklason,et al.  Antihuman factor V antibodies after use of relatively pure bovine thrombin. , 2005, The Annals of thoracic surgery.

[10]  L. Kraiss,et al.  Severe Coagulopathy following Intraoperative Use of Topical Thrombin , 2004, Annals of vascular surgery.

[11]  J. Zehnder,et al.  Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin. , 1990, Blood.

[12]  S. Israels,et al.  Development of Antibodies to Bovine and Human Factor V in Two Children After Exposure to Topical Bovine Thrombin , 1994, American Journal Of Pediatric Hematology/Oncology.

[13]  M. Kajitani,et al.  Severe Hemorrhagic Complication Due to Acquired Factor V Inhibitor After Single Exposure to Bovine Thrombin Product , 2000, Journal of cardiac surgery.

[14]  M. Runge,et al.  New tricks for old dogs: nonthrombotic effects of thrombin in vessel wall biology. , 2001, Circulation research.

[15]  J. Lawson The clinical use and immunologic impact of thrombin in surgery. , 2006, Seminars in thrombosis and hemostasis.

[16]  R. Lattes,et al.  Hemostasis With Absorbable Gauze (Oxidized Cellulose). , 1944, Annals of surgery.

[17]  T. Ortel,et al.  Topical thrombin and acquired coagulation factor inhibitors: Clinical spectrum and laboratory diagnosis , 1994, American journal of hematology.

[18]  W. Chapman,et al.  A phase 3, randomized, double-blind comparative study of the efficacy and safety of topical recombinant human thrombin and bovine thrombin in surgical hemostasis. , 2007, Journal of the American College of Surgeons.

[19]  W. Wagner,et al.  Comparative in vitro analysis of topical hemostatic agents. , 1996, The Journal of surgical research.

[20]  Erika Giste,et al.  Preclinical safety of recombinant human thrombin. , 2007, Regulatory toxicology and pharmacology : RTP.

[21]  W. Chapman,et al.  Phase 2, randomized, double‐blind, placebo‐controlled, multicenter clinical evaluation of recombinant human thrombin in multiple surgical indications , 2006, Journal of thrombosis and haemostasis : JTH.

[22]  M. Walther,et al.  Antibody induced coagulopathy from bovine thrombin use during partial nephrectomy. , 2001, The Journal of urology.

[23]  J. Spero Bovine thrombin-induced inhibitor of factor V and bleeding risk in postoperative neurosurgical patients. Report of three cases. , 1993, Journal of neurosurgery.

[24]  T. Ortel,et al.  Immunologic Impact and Clinical Outcomes After Surgical Exposure to Bovine Thrombin , 2001, Annals of surgery.

[25]  S. Israels,et al.  Acquired inhibitors to factors V and X after exposure to topical thrombin: interference with monitoring of low molecular weight heparin and warfarin. , 1997, The Journal of pediatrics.

[26]  W. Muntean,et al.  Inhibitor to factor V after exposure to fibrin sealant during cardiac surgery in a two‐year‐old child , 1994, Acta paediatrica.

[27]  A. Poynton,et al.  Bovine Thrombin Induces an Acquired Coagulopathy in Sensitized Patients Undergoing Revision Spinal Surgery: A Report of Two Cases , 2003, Spine.

[28]  T. Ortel,et al.  Exposure of mice to topical bovine thrombin induces systemic autoimmunity. , 2001, The American journal of pathology.

[29]  M. Wener,et al.  Iatrogenic immunization with bovine thrombin: a mechanism for prolonged thrombin times after surgery. , 1989, Annals of internal medicine.

[30]  N. Heaton,et al.  Comparison of a new fibrin sealant with standard topical hemostatic agents. , 2004, Archives of surgery.

[31]  Wesley K. Lew,et al.  A comparison of recombinant thrombin to bovine thrombin as a hemostatic ancillary in patients undergoing peripheral arterial bypass and arteriovenous graft procedures. , 2008, Journal of vascular surgery.

[32]  S. Rapaport,et al.  Clinical significance of antibodies to bovine and human thrombin and factor V after surgical use of bovine thrombin. , 1992, American journal of clinical pathology.

[33]  A. Imbriano [Blood coagulation]. , 1955, La Semana medica.

[34]  B. Brost,et al.  Development of antibodies to topical bovine thrombin after abdominal hysterectomy. A case report. , 2001, The Journal of reproductive medicine.

[35]  C. Takemoto,et al.  Acquired coagulation factor inhibitors in children after topical bovine thrombin exposure , 2007, Pediatric blood & cancer.

[36]  J. Amiral,et al.  Immunization by bovine thrombin used with fibrin glue during cardiovascular operations. Development of thrombin and factor V inhibitors. , 1993, Journal of Thoracic and Cardiovascular Surgery.

[37]  D. Hormuth,et al.  Antiphospholipid antibodies in left-ventricular assist system recipients after exposure to topical bovine thrombin. , 1999, Transplantation proceedings.

[38]  M. R. Jackson,et al.  Fibrin sealants in surgical practice: An overview. , 2001, American journal of surgery.