Medical College of Wisconsin
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Patients with quinine-induced immune thrombocytopenia have both "drug-dependent" and "drug-specific" antibodies. Blood 2006 Aug 01;108(3):922-7

Date

07/25/2006

Pubmed ID

16861345

Pubmed Central ID

PMC1895854

DOI

10.1182/blood-2006-01-009803

Scopus ID

2-s2.0-33746653756 (requires institutional sign-in at Scopus site)   97 Citations

Abstract

Immune thrombocytopenia induced by quinine and many other drugs is caused by antibodies that bind to platelet membrane glycoproteins (GPs) only when the sensitizing drug is present in soluble form. In this disorder, drug promotes antibody binding to its target without linking covalently to either of the reacting macro-molecules by a mechanism that has not yet been defined. How drug provides the stimulus for production of such antibodies is also unknown. We studied 7 patients who experienced severe thrombocytopenia after ingestion of quinine. As expected, drug-dependent, platelet-reactive antibodies specific for GPIIb/IIIa or GPIb/IX were identified in each case. Unexpectedly, each of 6 patients with GPIIb/IIIa-specific antibodies was found to have a second antibody specific for drug alone that was not platelet reactive. Despite recognizing different targets, the 2 types of antibody were identical in requiring quinine or desmethoxy-quinine (cinchonidine) for reactivity and in failing to react with other structural analogues of quinine. On the basis of these findings and previous observations, a model is proposed to explain drug-dependent binding of antibodies to cellular targets. In addition to having implications for pathogenesis, drug-specific antibodies may provide a surrogate measure of drug sensitivity in patients with drug-induced immune cytopenia.

Author List

Bougie DW, Wilker PR, Aster RH

Author

Richard H. Aster MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Antibodies
Humans
Immunoassay
Platelet Glycoprotein GPIIb-IIIa Complex
Platelet Glycoprotein GPIb-IX Complex
Platelet Membrane Glycoproteins
Quinine
Thrombocytopenia