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Prepublished online as a Blood First Edition Paper on September 25, 2003; DOI 10.1182/blood-2003-07-2229.

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2003-07-2229v1
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Submitted July 7, 2003
Accepted September 11, 2003

Antibodies against lepirudin are polyspecific and recognize epitopes on bivalirudin

Petra Eichler, Norbert Lubenow, Ulrike Strobel, and Andreas Greinacher*

Department of Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany

* Corresponding author; email: greinach{at}uni-greifswald.de.

Bivalirudin is a synthetic anti-thrombin, sharing a sequence of 11 amino acids with the recombinant hirudin lepirudin. We investigated whether anti-lepirudin-antibodies recognize epitopes on bivalirudin. Anti-lepirudin antibody positive sera of 43 patients, treated with lepirudin for heparin-induced thrombocytopenia, were analysed. Lepirudin- and bivalirudin coated microtiter plates were used for antibody testing in an ELISA system. Of the 43 sera containing antibodies binding to lepirudin, 22 (51.2%) contained antibodies that also recognized bivalirudin. Binding of these antibodies to bivalirudin was inhibited by >70% by preincubation with high doses of bivalirudin. However, if lepirudin coated microtiter plates were used, high concentrations of bivalirudin inhibited only 2 of the 43 positive sera by >30%. Therefore anti-hirudin antibodies must be polyspecific. The clinical consequences of this cross-reactivity are unknown but bivalirudin, targeted by antibodies of patients treated with lepirudin previously, could potentially boost antibody titres in such patients, or even trigger an immune response by itself. Clinically significant antibody formation in response to bivalirudin monotherapy has not been observed, however. Yet, as lepirudin and anti-lepirudin antibodies have recently been implicated in severe anaphylactic reactions, caution is warranted when using bivalirudin in patients previously treated with lepirudin.


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