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Blood, 1 August 2006, Vol. 108, No. 3, pp. 922-927.
Prepublished online as a Blood First Edition Paper on April 11, 2006; DOI 10.1182/blood-2006-01-009803.
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Submitted January 27, 2006
Accepted March 21, 2006
Patients with quinine-induced immune thrombocytopenia have both " drug-dependent " and " drug-specific " antibodies
Daniel W Bougie*, Peter R Wilker, and Richard H Aster
The Blood Research Institute, BloodCenter of Wisconsin
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
Blood Research Institute,BloodCenter of Wisconsin; Medical College of Wisconsin
* Corresponding author; email: dan.bougie{at}bcw.edu.
Immune thrombocytopenia induced by quinine and many
other drugs is caused by antibodies that bind to
platelet membrane glycoproteins 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
macromolecules by a mechanism that has not yet been
defined. How drug provides the stimulus for production
of such antibodies is also unknown. We studied seven
patients who experienced severe thrombocytopenia after
ingestion of quinine. As expected, drug-dependent,
platelet-reactive antibodies specific for glycoproteins
IIb/IIIa and/or Ib/IX were identified in each case.
Unexpectedly, each of six 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 two 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.
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