A Pilot Study on Probing of Imatinib Induced Platelet Dysfunction in Patients with Chronic Myeloid Leukemia-Chronic Phase and Absence of Associated Bleeding Manifestation: Trying to Solve an Enigma.

Abstract

Imatinib, the first Tyrosine Kinase Inhibitor (TKI) used for the treatment of chronic myeloid leukaemia (CML) has revolutionized the management by inhibiting BCR-ABL tyrosine kinase. According to earlier reports there are concerns regarding the adverse effect of imatinib on haemostasis by causing platelet dysfunction. Here we studied platelet function usingplatelet aggregometry, in 19 CML chronic phase (CML-CP) patients on imatinib therapy, in complete haematologic response (CHR). The median duration of imatinib therapy before performing the test was 154days. This study reveals that there are large inter-individual variations in platelet functions among imatinib treated patients and different levels of variability have been seen for different agonists. Most common aggregation abnormality (< 50% aggregation) was seen withlow dose collagen (1μg/ml) in 31.57% patients. Despite in-vitro platelet aggregation defects, none of the patients showed any bleeding symptoms. This enigma can possibly be explained by the fact that platelet specific agonists, epinephrine and collagen act in synergy for platelet aggregation compared against individual low dose agonists, supported by ex-vivo experiments in normal healthy control group (n = 5) (p value < 0.0004 for epinephrine, p value < 0.0001 for collagen). This experiment was also confirmed in a CML-CP patient. In future, more studies are needed to find out the exact mechanism of this inhibition.