Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions
Marie Levade, Elodie David, Cedric Garcia, Pierre-Alexandre Laurent, Sarah Cadot, Anne-Sophie Michallet, Jean-Claude Bordet, Constantine Tam, Pierre Sie, Loic Ysebaert, Bernard Payrastre
BLOOD | AMER SOC HEMATOLOGY | Published : 2014
The oral Bruton's tyrosine kinase inhibitor, ibrutinib, has recently demonstrated high efficiency in patients with relapsed B-cell malignancies. Occurrence of bleeding events has been reported in a subgroup of ibrutinib-treated patients. We demonstrate that ibrutinib selectively inhibits platelet signaling and functions downstream of the collagen receptor glycoprotein VI and strongly affects firm platelet adhesion on von Willebrand factor (VWF) under arterial flow. A longitudinal study of 14 patients indicated a correlation between occurrence of bleeding events and decreased platelet aggregation in response to collagen in platelet-rich plasma and firm adhesion on VWF under arterial flow. The..View full abstract
Awarded by Cancer Pharmacology of Toulouse Oncopole & Region (CAPTOR) project
This work was supported by grants from INSERM, Fondation Pour la Recherche Medicale, and the Cancer Pharmacology of Toulouse Oncopole & Region (CAPTOR) project (Investissements d'Avenir ANR11-PHUC001).