XXXX -induced @entity882 : drug-dependent GPIb/IX antibodies inhibit megakaryocyte and proplatelet production in vitro.

@entity1 @entity882 @entity1200 @entity4807 @entity5126
The development of @entity1200 is a well-recognized side effect of many drugs. @entity4807 - and @entity5126 -dependent antibodies are classic examples of drug-induced effects that cause severe, life-threatening @entity882 . 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 @entity4807 -induced @entity882 (QITP) @entity1 on highly pure Mks (98% glycoprotein IIb-positive [GPIIb(+)]; 92% GPIX(+)) derived from @entity1 CD34(+) cells cultured with @entity1 thrombopoietin. We demonstrate by flow cytometry and confocal microscopy that QITP IgGs bind Mks efficiently in the presence of @entity4807 . 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(+)/GPIba(+) 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.
