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.
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.
Chouhan
V D
VD
Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
De La Cadena
R A
RA
Nagaswami
C
C
Weisel
J W
JW
Kajani
M
M
Rao
A K
AK
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D001780:Blood Coagulation Tests; D002417:Cattle; D004844:Epistaxis / Q000209:etiology; D005165:Factor V / Q000276:immunology*; D005340:Fibrinogen / Q000276:immunology*; D006474:Hemorrhagic Disorders / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D006488:Hemostasis, Surgical; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D010974:Platelet Aggregation; D011183:Postoperative Complications / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D011486:Protein C / Q000378:metabolism; D013045:Species Specificity; D013917:Thrombin / Q000008:administration & dosage / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D011486:Protein C; D005165:Factor V; D005340:Fibrinogen; D013917:Thrombin