Tyrosine kinase inhibitor-induced platelet dysfunction in patients with chronic myeloid leukemia.
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.
Alfonso
A
Quintás-Cardama
Xin
X
Han
Hagop
H
Kantarjian
Jorge
J
Cortes
D001549:Benzamides; D001777:Blood Coagulation / Q000187:drug effects; D001791:Blood Platelet Disorders / Q000139:chemically induced*; D000069439:Dasatinib; D006262:Health; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology*; D010879:Piperazines / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D000069439:Dasatinib