Aspirin-Platelet Sensitivity in Patients with Essential Thrombocythemia: Role βfibrinogen G-455-a Gene Polymorphism

Essential thrombocythemia (ET) is a myeloid neoplasm characterized by platelet activation and thrombotic risk. Aspirin (ASA) is the standard therapy to normal platelet hyperaggregation and to prevent the thrombosis. It is reported that thrombocythaemic patients are ASA insensitive. It is debated if inherited thrombophilia increases the thrombocythemic platelet activation and, hence, the ASA platelet insensitivity. Therefore, we evaluated βFibrinogen G-455-A gene polymorphism, as thrombophilic molecular mutation associated with increased platelet aggregation, platelet count, β-thromboglobulin (β-TG) and platelet factor 4(PF4) as markers of platelet activation, fibrinogen (Fg), platelet functional activity (PFA), as indicator of ASA platelet sensitivity, clot formation time (CFT) and the maximum clot firmness (MCF), as indicators of aspirinated platelet contribution to clot firmness. We studied 40 patients (24 men, 16 women; mean age 56 years, range 37-77) with ET according to WHO criteria. The mean duration of disease was 11 years. All patients were on ASA 100 mg once daily. The βFibrinogen G455-A genotype was determined using a commercialized polymerase chain reaction kit with sequence-specific primers. Platelets were measured by automated analyzer. β-TG and PF4 were determined by ELISA. PFA, CFT and MCF were measured by Platelet Function Analyzer (PFA-100) and by ROTEM delta, respectively. All patients had heterozygous βFibrinogen G455-A. The mean platelet count was 441±72x109/L. All patients had normal Fg (244±47 mg/dl) high β-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 βFibrinogen G-455-A gene polymorphism does not affect the clonal platelet hyperaggregation in ET.