Effect of thrombopoietin receptor agonists on the apoptotic profile of platelets in patients with chronic immune thrombocytopenia
William Beau Mitchell, Mariana P Pinheiro, Nayla Boulad, David Kaplan, Michele N Edison, Bethan Psaila, Marissa Karpoff, Michael J White, Emma C Josefsson, Benjamin T Kile, James B Bussel
AMERICAN JOURNAL OF HEMATOLOGY | WILEY | Published : 2014
Platelet survival depends upon mediators of apoptosis e.g., Bcl-xL, Bax, and Bak, which are regulated by thrombopoietin (TPO)-mediated AKT signaling. Thrombopoietin receptor (TPO-R) signaling might decrease platelet and/or megakaryocyte apoptosis and increase the platelet count. This study therefore explored anti-apoptotic effects of TPO-R-agonists in vivo on platelets of patients with immune thrombocytopenia. Patients received eltrombopag or romiplostim for two weeks. Total, immature, and large platelet counts were assessed as were Bcl-xL inhibitor assay; Bcl-xL Western blot; and flow cytometric (FACS) analysis of the AKT-signaling pathway. Eight/ten patients had platelet responses to eltro..View full abstract
Awarded by Academy of Medical Sciences (AMS)
Awarded by National Institute for Health Research
JBB has received research funding from Amgen and Glaxo Smith Kline.