High Prevalence Of Aspirin-Resistance In Myeloproliferative Neoplasms

Aspirin is recommended and widely prescribed to MPN patients without any evaluation of its efficacy. We report on 46 patients followed in our institution for a Myeloproliferative Neoplasm and treated by low-dose aspirin (75 to 160 mg p. day) alone or aside a cytoreductive therapy, mainly hydroxy-urea ; on the occasion of a routine visit we measured the response of their platelets to arachidonic acid in order to assess their sensibility to aspirin. Most patients (25) had ET, 15 had PV, 4 had CML and 2 Myelofibrosis. Response to arachidonic acid was measured on a citrated whole blood sample using an impedance-based semi-automatic aggregometer (Multiplate®) ; TRAP (Thrombin Receptor Activating Peptide) aggregation was performed systematically as a positive control. In 20 patients out of 46 (43,5%) there was persistence of a significant aggregability to arachidonic acid defining the resistance to aspirin according to our reference values : 10/25 ET (38%), 9/15 PV (62%)and 1/4 LMC. These proportions are much higher than those we note in heart or vascular diseases as well as those reported in published series. The observance of aspirin treatment could be considered doubtful only in a minority of patients (5/46) ; as the resistance appeared more frequent in PV we could assume a biais linked to the utilization of whole blood, but most PV patients were well controlled and did not have an elevated hematocrit. In untreated or refractory ET patients, the persistence of an increased platelet count suggests that aspirin dosage was not adequate although there was no statistical significance between daily dose and resistance. We observed an ischemic complication (transient stroke) in a single patient whose platelet count was not controlled despite hydroxy-urea but remained sensible to aspirin.

We conclude that aspirin resistance is frequent in MPN treated with low-dose aspirin and that a monitoring is worth to increase the dose or change for another inhibitor.