Simultaneous occurrence of human antibodies directed against fibrinogen, thrombin, and factor V following exposure to bovine thrombin: effects on blood coagulation, protein C activation and platelet function

Thromb Haemost. 1997 Feb;77(2):343-9.


We describe a patient with severe epistaxis, prolonged coagulation tests and decreased plasma factor V following exposure to bovine topical thrombin. Patient IgG, but not normal IgG, showed binding to immobilized thrombin (bovine > human) and fibrinogen, and to factor V by Western blotting; the binding to thrombin was inhibited by hirudin fragment 54-65. Electron microscopy of rotary shadowed preparations showed complexes with IgG molecules attached near the ends of trinodular fibrinogen molecules. Patient IgG inhibited procoagulant, anticoagulant and cell-stimulating functions of thrombin demonstrated by inhibition of fibrinogen clotting, protein C activation and platelet aggregation; thrombin hydrolysis of S-2238 was not inhibited. The results suggest that the antibody is targeted against anion-binding exosite and not catalytic site of thrombin. Antifibrinogen antibodies have not been reported in patients exposed to bovine thrombin. There is a pressing need to re-evaluate the role of bovine thrombin as a therapeutic agent.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Antibody Specificity
  • Autoantibodies / biosynthesis*
  • Autoantibodies / immunology
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / chemically induced*
  • Autoimmune Diseases / immunology
  • Blood Coagulation Tests
  • Cattle
  • Epistaxis / etiology
  • Factor V / immunology*
  • Fibrinogen / immunology*
  • Hemorrhagic Disorders / blood
  • Hemorrhagic Disorders / chemically induced*
  • Hemorrhagic Disorders / immunology
  • Hemostasis, Surgical
  • Humans
  • Immunoglobulin G / immunology
  • Male
  • Platelet Aggregation
  • Postoperative Complications / blood
  • Postoperative Complications / chemically induced*
  • Postoperative Complications / immunology
  • Protein C / metabolism
  • Species Specificity
  • Thrombin / administration & dosage
  • Thrombin / immunology*


  • Autoantibodies
  • Immunoglobulin G
  • Protein C
  • Factor V
  • Fibrinogen
  • Thrombin