Medline ® Abstract for Reference 83
of 'Clinical use of tyrosine kinase inhibitors for chronic myeloid leukemia'
Tyrosine kinase inhibitor-induced platelet dysfunction in patients with chronic myeloid leukemia.
Quintás-Cardama A, Han X, Kantarjian H, Cortes J
Blood. 2009;114(2):261. Epub 2009 May 4.
Dasatinib is associated with increased risk of bleeding among patients with chronic myeloid leukemia, even in the absence of thrombocytopenia, suggesting the presence of a hemostatic defect. We tested platelet aggregation in 91 patients with chronic myeloid leukemia in chronic phase either off-therapy (n = 4) or receiving dasatinib (n = 27), bosutinib (n = 32), imatinib (n = 19), or nilotinib (n = 9). All but 3 patients simultaneously receiving imatinib and warfarin had normal coagulation studies. All 4 patients off therapy had normal platelet aggregation. Impaired platelet aggregation on stimulation with arachidonic acid, epinephrine, or both was observed in 70%, 85%, and 59% of patients on dasatinib, respectively. Eighty-five percent of patients on bosutinib, 100% on nilotinib, and 33% on imatinib had normal platelet aggregation. Dasatinib 400 nM induced rapid and marked prolongation of closure time to collagen/epinephrine in normal whole blood on the PFA-100 system. In conclusion, dasatinib and, to some extent, imatinib produce abnormalities in platelet aggregometry testing.
Departments of Leukemia, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.