The Functional Platelet Response to Aspirin in Patients with Essential Thrombocythemia

The essential thrombocythemia (ET) is a myeloid neoplasm characterized by platelet hyperreactivity and thrombosis. The daily low-dose aspirin (ASA) is a cornerstone in the prevention of the thrombotic events. In the ET an accelerated platelet turnover translates in a renewal of the drug target shortening the duration of cyclooxygenase (COX-1) inhibition and may dictate new dosing strategies particularly ASA "low-responders" patients. Therefore, we evaluated platelet count, β-thromboglobulin (β-TG) and platelet factor 4 (PF4), as markers of platelet activation, the platelet function activity (PFA), as indicator of ASA platelet sensitivity and the clotting time (CT), as indicator of aspirinated platelet contribution to clot formation. We studied 60 patients (20 men, 40 women; mean age 51 years, range 32-70) with ET according to WHO criteria. The mean duration of disease was 11 years. All patients were on ASA 100 mg once daily. Of the 60 patients, 45 were on anagrelide hydrochloride (daily dose 1.5 mg) (10 men, 35 women), 15 were on hydroxyurea (daily dose 2 mg) (10 men 5 women). None had inherited or acquired thrombotic risk factors. Sixty subjects served as controls. Platelets were measured by automated analyzer. β-TG and PF4 were determined by ELISA. ASA platelet sensitivity and CT were measured by Platelet Function Analyzer (PFA-100) and by ROTEM delta, respectively. The mean platelet count was 455±200x109/L. All patients had normal β-TG and PF4 (12±5 IU/ml and 4±1 IU/ml), prolonged C/EPI closure time (T, unit: s, n.v. 84-160 s) (249±40 s), normal CT (CT, unit: s. n.v. 100-240 s) ( 110±20 s). These findings suggest that in ET patients the daily low-dose ASA represents an optimal dosing strategy.