Declined presentation Human platelet antigen genotype : effect on aspirinated platelets in patients with essential thrombocythemia

Abstract

Essential thrombocythemia (ET) is a myeloid neoplasm characterized by platelet hyperaggregation. Low-dose aspirin (ASA) is the standard treatment to normal platelet function and to prevent the thrombosis. It is debated if inherited thrombophilia affects the ASA platelet responsiveness. Therefore, we evaluated human platelet antigen-1 (HPA-1) gene polymorphism, as thrombophilic molecular mutation associated with platelet hyperfunction, platelet count, b-thromboglobulin (b-TG) and platelet factor 4 (PF4), as markers of platelet activation, the platelet functional activity (PFA) as indicator of ASA platelet sensitivity, clot formation time (CFT) and the maximum clot firmness (MCF), as indicator of aspirinated platelet contribution to clot firmness. We studied 48 patients (16 men, 32 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. Fifty subjects served as controls. The HPA-1 genotype was determined using a commercialized polymerase chain reaction kit with sequence-specific primers. Platelets were measured by automated analyzer. b-TG and PF4 were determined by ELISA. ASA platelet sensitivity, CFT and MCF were measured by Platelet Function Analyzer (PFA-100) and by ROTEM delta, respectively. Of 48 patients, 36 were HPA-1a/1a and 12 were HPA-1a/1b. The mean platelet count was 462±240x109/L. All patients had high b-TG and PF4 (244±15 IU/ml vs 20±11 IU/ml and 162±56 IU/ml vs 6±2 IU/ml, respectively) (p<.0001 and p<.0001, respectively), prolonged C/EPI closure time (CT, unit: s, n.v. 84-160 s) (252±48 s), normal CFT (CFT, unit: s, n.v. 30-110 s) (50±7s) and MCF (MCF, unit: mm, n.v. 50-72 mm) (71±2 mm). These findings suggest that HPA-1 gene polymorphism does not affect aspirinated platelets responsiveness in patients with ET as assessed by PFA-100 and thromboelastometry.