Ponatinib Exerts an Inhibitory Effect on Collagen-induced Platelet Aggregation and Generation of Coated-Platelets

This is the authors' abstract. We don't add key points for this paper.

BACKGROUND/AIM: BCR-ABL tyrosine kinase inhibitors (TKIs) are exceptionally effective drugs in the treatment of chronic myeloid leukemia, nevertheless, TKIs have also an effect on platelets. We aimed to investigate the effect of a third-generation TKI, ponatinib on platelet functions. MATERIALS AND METHODS: Collagen-induced platelet aggregation and coated-platelet formation were examined using in vitro and in ex vivo samples of patients on ponatinib therapy. RESULTS: In platelet rich plasma of healthy volunteers, ponatinib at a supra-therapeutic concentration (1,000 nM) significantly impaired collagen induced platelet aggregation (p≤0.01) and reduced the formation of coated-platelets at 150 nM ponatinib concentration (p≤0.05). In addition, upon glycoprotein VI (GPVI) receptor activation, a significantly lower percentage of PAC1 binding platelets (p≤0.05) was observed at 1,000 nM final concentration of ponatinib. Platelets, isolated from patients on ponatinib therapy showed impaired collagen elicited aggregation response, already in pre-dose samples compared to healthy donors. CONCLUSION: The therapeutic concentration of ponatinib impairs platelet activation processes elicited by GPVI receptor agonists.

May warrant bleeding monitoring in ponatinib patients; hypothesis-generating for GPVI effects in vivo.