TY - JOUR T1 - Ponatinib Exerts an Inhibitory Effect on Collagen-induced Platelet Aggregation and Generation of Coated-Platelets JF - Anticancer Research JO - Anticancer Res SP - 4867 LP - 4874 DO - 10.21873/anticanres.15300 VL - 41 IS - 10 AU - GABRIELLA MEZEI AU - PÉTER BATÁR AU - LAURA KOZMA AU - ÁRPÁD ILLÉS AU - JÁNOS KAPPELMAYER AU - ILDIKÓ BEKE DEBRECENI Y1 - 2021/10/01 UR - http://ar.iiarjournals.org/content/41/10/4867.abstract N2 - 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. ER -