(Circulation. 1999;100:1528-1532.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Generation of Anti-Hirudin Antibodies in Heparin-Induced Thrombocytopenic Patients Treated With R-Hirudin
From the First Department of Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg.
Correspondence to Job Harenberg, MD, Professor of Medicine, First Department of Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer, 68167 Mannheim, Germany. E-mail J-Harenberg{at}t-online.de
Background—Hirudin is a small
protein with strong thrombin inhibition that may be antigenic. The
generation and disappearance of anti-hirudin antibodies were
investigated in patients with heparin-induced thrombocytopenia who were
treated with recombinant hirudin (r-hirudin) for 
5 days.
Methods and Results—The IgA, IgE, IgG, and IgM isotypes of
anti-hirudin antibodies were determined by ELISA before and after the
start of r-hirudin therapy. A total of 56% of patients (13 of 23)
developed 1 antibody isotype during therapy. No IgE antibodies were
generated. IgA, IgG, and IgM antibodies were detected in 30% (7 of
23), 52% (12 of 23), and 17% (4 of 23) of patients, respectively.
Four patients generated only IgG, 2 patients developed either IgM or
IgG and IgM, 5 patients IgG and IgA, and 2 patients IgG, IgM, and IgA
antibodies. IgM antibodies disappeared within 8 days of the cessation
of r-hirudin. IgA and IgG antibodies disappeared within 1 year in all
but 1 patient. Binding of purified IgG to r-hirudin in IgG
antibody–positive patients (n=7) was demonstrated by competitive ELISA
for r-hirudin. Of the 7 IgG antibody samples, 1 each neutralized or
enhanced the anticoagulant activity of r-hirudin.
Conclusions—R-hirudin may be antigenic in patients with heparin-induced thrombocytopenia. More comprehensive investigations will be required to determine the biological relevance of this and to establish the antibody-generation pattern in other diseases.
Key Words: antibodies • anticoagulants • proteins • thrombosis
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