Platelet thromboxane inhibition by low‐dose aspirin in polycythemia vera: Ex vivo and in vivo measurements and in silico simulation

Petrucci, Giovanna; Giaretta, Alberto; Ranalli, Paola; Cavalca, Viviana; Dragani, Alfredo; Porro, Benedetta; Hatem, Duaa; Habib, Aı̈da; Tremoli, Elena; Patrono, Carlo; Rocca, Bianca

doi:10.1111/cts.13415

Cited by 8 publications

(10 citation statements)

References 51 publications

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“…The primary metabolite of arachidonic acid, thromboxane A2 (TXA2), can be inhibited by aspirin. Aspirin’s therapeutic effectiveness in reducing the risk of atherothrombosis and its side effect of bleeding can be explained by the fact that TXA2 is a potent inducer of platelet aggregation ( Patrono, 2015 ; Petrucci et al, 2022 ). Controversial recommendations made by European and US guidelines reflect the uncertainty over the relative benefits and risks of using aspirin for the primary prevention of CVD.…”

Section: Discussionmentioning

confidence: 99%

Low- or high-dose preventive aspirin use and risk of death from all-cause, cardiovascular disease, and cancer: A nationally representative cohort study

Chen

Chen²,

Liao³

et al. 2023

Front. Pharmacol.

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Background and aim: For a long time, aspirin has been recommended for the prevention of cardiovascular disease (CVD). However, results of long-term effects of aspirin use on the risk of CVD and all-cause death as well as cause-specific mortality are not consistent. This study aims to investigate the relationship between low- or high-dose preventive aspirin use and the risk of death from all-cause, CVD, and cancer among US adults aged 40 years and older.Methods: A prospective cohort study was conducted by utilizing four cycles of the National Health and Nutrition Examination Survey (NHANES) and linked 2019 mortality files. Cox proportional hazard models accounting for multiple covariates were used to calculate hazard ratio (HR) and 95% confidence interval (CI) for the associations between low- or high-dose aspirin use and risk of death.Results: A total of 10,854 individuals (5,364 men and 5,490 women) were enrolled in the study. During a median follow-up of 4.8 years, 924 death events including 294 CVD death and 223 cancer death were documented. We found no evidence that taking low-dose aspirin decreased the chance of dying from any cause (HR: 0.92, 95% CI: 0.79–1.06), CVD (HR: 1.03, 95% CI: 0.79–1.33), or cancer (HR: 0.80, 95% CI: 0.60–1.08). High-dose aspirin users had a higher risk of CVD death compared to participants who had never used aspirin (HR: 1.63, 95% CI: 1.11–2.41).Conclusion: Using low-dose aspirin has no effect on the risk of death from any causes, whereas taking high doses of aspirin increases the risk of CVD death.

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Section: Discussionmentioning

confidence: 99%

Low- or high-dose preventive aspirin use and risk of death from all-cause, cardiovascular disease, and cancer: A nationally representative cohort study

Chen

Chen²,

Liao³

et al. 2023

Front. Pharmacol.

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“…Urine samples from 703 subjects (51 healthy individuals 19 , 20 , 61 patients with diabetes mellitus 20 , 21 [Petrucci et al accepted for publication], 242 patients with hematologic 22 , 23 and 349 with solid cancers 10 were assayed a first time in previously-published studies 10 , 19 – 23 [Petrucci et al accepted for publication]. In the original protocols, all urine samples were collected from study participants and frozen within 2–3 h from collection at −40 °C, under controlled temperature (PDF 440W, EVERmed, Medical Refrigeration; Motteggiana, MN and KBPF600 PP, KW Apparecchi Scientifici srl, Monteriggioni, SI, all in Italy) until first measurement.…”

Section: Methodsmentioning

confidence: 99%

“…For creatinine, 610 urine samples from 53 healthy individuals 19 , 20 , 189 patients with diabetes mellitus [Petrucci et al submitted], 110 patients with hematologic 21 , 22 , and 258 with solid cancers 10 , were assayed for a second time for creatinine using a commercial kit (Creatinine Colorimetric Detection Kit; Enzo Life Sciences, Farmingdale, NY, USA). The inter-assay coefficient of variation using a commercial standard (Creatinine Standard, Cayman Chemical) was 7% over the study duration (n = 523 determinations).…”

Section: Methodsmentioning

confidence: 99%

Effect of very long-term storage and multiple freeze and thaw cycles on 11-dehydro-thromboxane-B2 and 8-iso-prostaglandin F2α, levels in human urine samples by validated enzyme immunoassays

Petrucci,

Hatem,

Langley

et al. 2024

Sci Rep

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Biological samples are often frozen and stored for years and/or thawed multiple times, thus assessing their stability on long-term storage and repeated freeze–thaw cycles is crucial. The study aims were to assess:—the long-term stability of two major enzymatic and non-enzymatic metabolites of arachidonic acid, i.e. urinary 11-dehydro-thromboxane-(Tx) B2, 8-iso-prostaglandin (PG)F2α, and creatinine in frozen urine samples;—the effect of multiple freeze–thaw cycles. Seven-hundred and three urine samples measured in previously-published studies, stored at −40 °C, and measured for a second time for 11-dehydro-TxB2 (n = 677) and/or 8-iso-PGF2α (n = 114) and/or creatinine (n = 610) were stable over 10 years and the 2 measurements were highly correlated (all rho = 0.99, P < 0.0001). Urine samples underwent 10 sequential freeze–thaw cycles, with and without the antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (10 mM); urinary 11-dehydro-TxB2 and creatinine were stable across all cycles (11-dehydro-TxB2: 100.4 ± 21%; creatinine: 101 ± 7% of baseline at cycle ten; n = 17), while 8-iso-PGF2α significantly increased by cycle 6 (151 ± 22% of baseline at cycle ten, n = 17, P < 0.05) together with hydrogen peroxide only in the absence of antioxidant. Arachidonic acid metabolites and creatinine appear stable in human urines stored at −40 °C over 10 years. Multiple freeze–thaw cycles increase urinary 8-iso-PGF2α in urine samples without antioxidants. These data are relevant for studies using urine samples stored over long-term and/or undergoing multiple freezing–thawing.

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“…It is interesting to note that in a different myeloproliferative neoplasm (ie, polycythemia vera), only 1 out of 3 patients treated with low-dose aspirin displayed less-than-maximal inhibition of platelet TXA 2 production. These patients were characterized by significantly higher platelet count and platelet-count corrected serum TXB 2 than those with adequate inhibition [ 57 ].…”

Section: Aspirin and Precision Dosingmentioning

confidence: 99%

“…Dotted lines indicate the values of 3 (blue), 6 (gold), and 9 (red) ng/mL of serum TXB 2 , corresponding to the 99%, 98%, and 97% inhibition levels of serum TXB 2 , respectively, measured in healthy subjects. Reproduced modified from reference [ 57 ] with permission from Wiley. …”

Section: Aspirin and Precision Dosingmentioning

confidence: 99%

Precision antiplatelet therapy

Rocca¹,

Patrono²

2023

Research and Practice in Thrombosis and Haemostasis

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Platelet thromboxane inhibition by low‐dose aspirin in polycythemia vera: Ex vivo and in vivo measurements and in silico simulation

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 8 publications

References 51 publications

Low- or high-dose preventive aspirin use and risk of death from all-cause, cardiovascular disease, and cancer: A nationally representative cohort study

Low- or high-dose preventive aspirin use and risk of death from all-cause, cardiovascular disease, and cancer: A nationally representative cohort study

Effect of very long-term storage and multiple freeze and thaw cycles on 11-dehydro-thromboxane-B2 and 8-iso-prostaglandin F2α, levels in human urine samples by validated enzyme immunoassays

Precision antiplatelet therapy

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