Poster No. 005 Platelet Thromboxane Inhibition by Low-Dose Aspirin in Polycythemia Vera:Ex Vivo and In Vivo Measurements and In Silico Simulation

Abstract Background Low-dose aspirin is currently recommended for patients with polycythemia vera (PV), a myeloproliferative neoplasm with increased risk of arterial and venous thromboses. Based on aspirin pharmacodynamics in essential thrombocythemia, a twice-daily regimen is recommended for PV patients deemed at particularly high thrombotic risk. Methods We investigated the effects of low-dose aspirin on platelet cyclooxygenase activity and in vivo platelet activation in 49 PV patients, as assessed by serum thromboxane (TX)B2 and urinary TXA2/TXB2 metabolite (TXM) measurements, respectively. A previously described pharmacokinetic-pharmacodynamic in silico model was used to simulate the degree of platelet TXA2 inhibition by once-daily and twice-daily aspirin, and to predict the effect of missing an aspirin dose during qd and bid regimens. Results Serum TXB2 averaged 8.2 [1.6–54.7] ng/ml and significantly correlated with the platelet count (rho = 0.39) and urinary TXM (rho = 0.52) in multivariable analysis. One-third of aspirin-treated PV patients displayed less-than-maximal platelet TXB2 inhibition, and were characterized by significantly higher platelet counts and platelet-count corrected serum TXB2 than those with adequate inhibition. Eight PV patients were sampled again after 12 ± 4 months, and had reproducible serum TXB2 and urinary TXM values. The in silico model predicted complete inhibition of platelet-derived TXB2 by bid aspirin, a prediction verified in a PV patient with the highest TXB2 value while on aspirin qd and treated short-term with a bid regimen. Conclusions In conclusion, one in three PV patients on low-dose aspirin display less-than-maximal inhibition of platelet TXA2 production. A personalized approach to antiplatelet therapy can be guided by serum TXB2 measurements.