Antibodies against lepirudin are polyspecific and recognize epitopes on bivalirudin

被引:36
作者
Eichler, P [1 ]
Lubenow, N [1 ]
Strobel, U [1 ]
Greinacher, A [1 ]
机构
[1] Univ Greifswald, Sauerbruchstr Diagnost Zentrum, Inst Immunol & Transfus Med, Dept Immunol & Transfus Med, D-17487 Greifswald, Germany
关键词
D O I
10.1182/blood-2003-07-2229
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Bivalirudin is a synthetic antithrombin sharing a sequence of 11 amino acids with the recombinant hirudin lepirudin. We investigated whether antilepirudin antibodies recognize epitopes on bivalirudin. Antilepirudin anti body-positive sera of 43 patients, treated with lepirudin for heparin-induced thrombocytopenia, were analyzed. Lepirudin- and bivalirudin-coated microtiter plates were used for antibody testing in an enzyme-linked immunosorbent assay (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 more than 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 more than 30%. Therefore antihirudin 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 titers 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 antilepirudin 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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收藏
页码:613 / 616
页数:4
相关论文
共 27 条
[1]   STUDIES FOR REVEALING A POSSIBLE SENSITIZATION TO HIRUDIN AFTER REPEATED INTRAVENOUS INJECTIONS IN BABOONS [J].
BICHLER, J ;
GEMMERLI, R ;
FRITZ, H .
THROMBOSIS RESEARCH, 1991, 61 (01) :39-51
[2]   Acute urticaria caused by subcutaneous recombinant hirudin: Evidence for an IgG-mediated hypersensitivity reaction [J].
Bircher, AJ ;
Czendlik, CH ;
Messmer, SL ;
Muller, P ;
Howald, H .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1996, 98 (05) :994-996
[3]   TREATMENT WITH BIVALIRUDIN (HIRULOG) AS COMPARED WITH HEPARIN DURING CORONARY ANGIOPLASTY FOR UNSTABLE OR POSTINFARCTION ANGINA [J].
BITTL, JA ;
STRONY, J ;
BRINKER, JA ;
AHMED, WH ;
MECKEL, CR ;
CHAITMAN, BR ;
MARAGANORE, J ;
DEUTSCH, E ;
ADELMAN, B .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 333 (12) :764-769
[4]  
CHAMBERLIN JR, 1995, CAN J CARDIOL, V11, P511
[5]  
CLOSE P, 1994, CORONARY ARTERY DIS, V5, P943
[6]  
Eichler P, 2000, BLOOD, V96, P2373
[7]   HIRULOG IN THE TREATMENT OF UNSTABLE ANGINA - RESULTS OF THE THROMBIN INHIBITION IN MYOCARDIAL-ISCHEMIA (TIMI) 7 TRIAL [J].
FUCHS, J ;
CANNON, CP ;
BRAUNWALD, E ;
ANTMAN, EM ;
MCCABE, CH ;
DEFEOFRAULINI, T ;
SOLLECITO, B ;
WALLMAN, L ;
TUDOR, G ;
WILLIAMS, DO ;
SHARAF, B ;
FERREIRA, P ;
MIELE, N ;
CHAITMAN, B ;
STOCKE, K ;
HENNEKENS, C ;
KELTON, J ;
FRIESINGER, GC ;
GERSH, B ;
GORLIN, R ;
BORZAK, S ;
GOLDBERG, N ;
HENRY, TD ;
THOMPSON, C ;
KRAFT, PL ;
DOUTHAT, L ;
PALISAITIS, D ;
GAUDETTE, G ;
HERSON, S ;
DAUM, R ;
CAREY, G ;
PALMERI, S ;
CASAZZA, L ;
SEQUEIRA, R ;
DEMARCENA, E ;
PRIETO, C ;
LAPSLEY, D ;
WARNICA, JW ;
CHURCHILLSMITH, T ;
GRANBERG, L ;
DIVER, DJ ;
MARBLE, S ;
MUELLER, H ;
COSICO, J ;
MAGORIEN, R ;
WILMER, J ;
JULIEN, R ;
LEYA, F ;
GALBRAITH, E ;
MCKENDALL, GR .
CIRCULATION, 1995, 92 (04) :727-733
[8]   USE OF HIRULOG IN THE PREVENTION OF VENOUS THROMBOSIS AFTER MAJOR HIP OR KNEE SURGERY [J].
GINSBERG, JS ;
NURMOHAMED, MT ;
GENT, M ;
MACKINNON, B ;
SICURELLA, J ;
BRILLEDWARDS, P ;
LEVINE, MN ;
PANJU, AA ;
POWERS, P ;
STEVENS, P ;
TURPIE, AGG ;
WEITZ, J ;
BULLER, HR ;
TENCATE, JW ;
NEEMEH, J ;
ADELMAN, B ;
FOX, I ;
MARAGANORE, J ;
HIRSH, J .
CIRCULATION, 1994, 90 (05) :2385-2389
[9]   Anaphylactic and anaphylactoid reactions associated with lepirudin in patients with heparin-induced thrombocytopenia [J].
Greinacher, A ;
Lubenow, N ;
Eichler, P .
CIRCULATION, 2003, 108 (17) :2062-2065
[10]   Antihirudin antibodies following low-dose subcutaneous treatment with desirudin for thrombosis prophylaxis after hip-replacement surgery:: incidence and clinical relevance [J].
Greinacher, A ;
Eichler, P ;
Albrecht, D ;
Strobel, U ;
Pötzsch, B ;
Eriksson, BI .
BLOOD, 2003, 101 (07) :2617-2619