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Thromb Haemost 1992; 67(02): 193-199
DOI: 10.1055/s-0038-1648411
Original Articles
Schattauer GmbH Stuttgart

Partial Characterization of an Autoantibody Recognizing the Secondary Binding Site(s) of Thrombin in a Patient with Recurrent Spontaneous Arterial Thrombosis

J M Costa
Laboratoire d’Hémostase et Centre Claude Bernard de Recherche sur les Maladies vasculaires périphériques, Hôpital Broussais, Paris, France
,
J N Fiessinger
Laboratoire d’Hémostase et Centre Claude Bernard de Recherche sur les Maladies vasculaires périphériques, Hôpital Broussais, Paris, France
,
L Capron
Laboratoire d’Hémostase et Centre Claude Bernard de Recherche sur les Maladies vasculaires périphériques, Hôpital Broussais, Paris, France
,
M Aiach
Laboratoire d’Hémostase et Centre Claude Bernard de Recherche sur les Maladies vasculaires périphériques, Hôpital Broussais, Paris, France
› Author Affiliations
Further Information

Publication History

Received 02 July 1991

Accepted after revision 21 August 1991

Publication Date:
02 July 2018 (online)

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Summary

A patient with an 18 year history of recurrent arterial thrombosis and no evidence of atherosclerosis or embolism of cardiac origin presented with a prolonged thrombin clotting time when performed with human thrombin. The bovine thrombin clotting time was only slightly prolonged. During 30 months of follow-up, the thrombin time fluctuated, but remained prolonged. The patient has been treated with an oral anticoagulant for the past 8 years, with no thrombotic recurrence.

The inhibitor activity was due to the presence of polyclonal IgGs which bound to thrombin-Sepharose. The influence of IgGs purified from the patient’s serum was compared to the influence of normal IgGs in several systems exploring the catalytic activity of thrombin and the binding of the enzyme to macromolecular substrates through secondary binding site(s). We found that the IgGs did not impair the catalytic activity toward small synthetic substrates, but inhibited the binding of thrombin to fibrinogen, thrombomodulin and heparin cofactor II. Such proteins are known to require a secondary binding site of thrombin to interact with the enzyme.

The anti-thrombin antibody might have resulted from an abnormal generation of thrombin. This would be the consequence of the process favouring thrombosis. Alternatively, the autoantibody might have favoured thrombosis primarily, by impairing natural antithrombotic mechanisms triggered by thrombin.

 

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