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المؤلفPetrucci, Giovanna
المؤلفGiaretta, Alberto
المؤلفRanalli, Paola
المؤلفCavalca, Viviana
المؤلفDragani, Alfredo
المؤلفPorro, Benedetta
المؤلفHatem, Duaa
المؤلفHabib, Aida
المؤلفTremoli, Elena
المؤلفPatrono, Carlo
المؤلفRocca, Bianca
تاريخ الإتاحة2023-07-12T04:38:02Z
تاريخ النشر2022-12-01
اسم المنشورClinical and Translational Science
المعرّفhttp://dx.doi.org/10.1111/cts.13415
الاقتباسPetrucci, G, Giaretta, A, Ranalli, P, et al. Platelet thromboxane inhibition by low-dose aspirin in polycythemia vera: Ex vivo and in vivo measurements and in silico simulation. Clin Transl Sci. 2022; 15: 2958- 2970. doi:10.1111/cts.13415
الرقم المعياري الدولي للكتاب17528054
معرّف المصادر الموحدhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85139426245&origin=inward
معرّف المصادر الموحدhttp://hdl.handle.net/10576/45377
الملخصLow-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 patients with PV deemed at particularly high thrombotic risk. We investigated the effects of low-dose aspirin on platelet cyclooxygenase activity and in vivo platelet activation in 49 patients with PV, 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 (q.d.) and twice-daily (b.i.d.) aspirin, and to predict the effect of missing an aspirin dose during q.d. and b.i.d. regimens. Serum TXB2 averaged 8.2 (1.6–54.7) ng/ml and significantly correlated with the platelet count (γ = 0.39) and urinary TXM (γ = 0.52) in multivariable analysis. One-third of aspirin-treated patients with PV 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 patients with PV 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 b.i.d. aspirin, a prediction verified in a patient with PV with the highest TXB2 value while on aspirin q.d. and treated short-term with a b.i.d. regimen. In conclusion, one in three patients with PV on low-dose aspirin display less-than-maximal inhibition of platelet TXA2 production. Serum TXB2 measurement can be a valuable option to guide precision dosing of antiplatelet therapy in patients with PV.
راعي المشروعSupported by Cancer Research UK (Catalyst Award–Aspirin for Cancer Prevention Collaboration C569/A24 to C.P. and B.R.).
اللغةen
الناشرWiley
الموضوعAspirin
polycythemia vera
Ex vivo
vivo measurements
silico simulation
العنوانPlatelet thromboxane inhibition by low-dose aspirin in polycythemia vera: Ex vivo and in vivo measurements and in silico simulation
النوعArticle
الصفحات2958 - 2970
رقم العدد12
رقم المجلد15
ESSN1752-8062


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