Effect of Imatinib Mesylate on Platelet Aggregation Abnormalities in BCR-ABL + CML Patients

Bleeding and thrombotic events complicate the clinical course of chronic myeloproliferative disorders (CMPDs). A spectrum of platelet aggregation abnormalities have been described in CML. Clonal involvement of megakaryocytopoiesis is regarded as the main origin of these abnormalities. Effects of cytoreductive drugs on platelet aggregation abnormalities have been studied which showed no significant corrective effect. Effect of Imatinib mesylate on platelet aggregation abnormalities has not been studied so far. Our study aims at assessing the effect of imatinib mesylate on platelet aggregation abnormalities in BCR-ABL positive CML patients. A total of 50 newly diagnosed BCR-ABL positive CML patients and 30 normal healthy volunteers were enrolled in the study. BCR-ABL by RT-PCR and Platelet aggregation parameters by CHRONOLOG aggregometer using arachidonic acid (AA), collagen, adrenaline (ADR), adenosine diphosphate (ADP) and ristocetin as agonists were measured both at diagnosis and after a minimum of 3 months of imatinib therapy. Platelet aggregation parameters measured for each agonist were Degree of aggregation (DOA) and Rate of Aggregation (ROA). DOA was calculated by increase of transmissions for 1 minute/total maximum transmissions in 2 minutes measurement of platelet aggregation and expressed as percentage. ROA was calculated as the number of 1mm squares under the platelet aggregation curve in 60 seconds. These parameters were calculated for each agonist for all patients and controls and their mean ± 2SD were analyzed. Forty-eight cases were in chronic phase (CP), accelerated (AP) and blast phase (BP) constituted one each. DOA and ROA parameters in 39/48(81%) cases in CP and both AP and BP cases measured with ADP, AA, and ADP as agonists in the pre-imatinib phase showed a statistically significant lower values compared to healthy controls. 3/48 (6%)CP cases showed hyper aggregation with ADR and 6/48(13%) showed normal aggregation parameters. In the post-imatinib phase, aggregation parameters normalized in 32/39 CP cases. AP and BP cases showed persistently lower values. No significant difference is noted in parameters measured using ristocetin and collagen as agonists when compared among pre and post imatinib phases and controls. The normalization of aggregation parameters may be attributed to either partial or complete suppression of clonal abnormal megakaryocytopoiesis and restoration of normal megakaryocytopoiesis by imatinib mesylate therapy in BCR-ABL positive CML.