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Quinine-induced thrombocytopenia: drug-dependent GPIb/IX antibodies inhibit megakaryocyte and proplatelet production in vitro.

Author(s): Perdomo J, Yan F, Ahmadi Z, Jiang XM, Stocker R, Chong BH

Affiliation(s): Department of Medicine, St George Clinical School, University of New South Wales, Gray Street, Kogarah, Australia.

Publication date & source: 2011-06-02, Blood., 117(22):5975-86. Epub 2011 Apr 12.

Publication type: In Vitro; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

The development of immune cytopenias is a well-recognized side effect of many drugs. Quinine- and quinidine-dependent antibodies are classic examples of drug-induced effects that cause severe, life-threatening thrombocytopenia. Whereas the effects of drug-dependent antibodies on platelets have been well documented, their effects on megakaryocyte (Mk) biology are still unclear. We analyzed sera from several quinine-induced thrombocytopenia (QITP) patients on highly pure Mks (98% glycoprotein IIb-positive [GPIIb(+)]; 92% GPIX(+)) derived from human CD34(+) cells cultured with human thrombopoietin. We demonstrate by flow cytometry and confocal microscopy that QITP IgGs bind Mks efficiently in the presence of quinine. Incubation of day-4 Mks with QITP sera or purified IgG resulted in induction of apoptosis, a significant decrease in cell viability, and an increase in cell death. Furthermore, QITP sera preferentially reduced the number of late GPIX(+)/GPIbalpha(+) Mks and the number of receptors per cell in the surviving population. Ploidy distribution, lobularity, and average cell size of Mks remained unchanged after treatment. In addition, treated Mks showed a marked decrease in their proplatelet production capacity, suggesting that drug-dependent antibodies hinder platelet production. Therefore, QITP antibodies considerably reduce the proplatelet production capabilities of Mks despite undetectable effects on DNA content, morphology, and cell size.

Page last updated: 2011-12-09

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