Thrombotic complications in essential thrombocythemia (ET): Clinical facts and biochemical riddles

Petrides, Petro E.; Siegel, Fabian

doi:10.1016/j.bcmd.2005.12.031

Cited by 30 publications

(24 citation statements)

References 39 publications

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“…8 Hemorrhagic complications are less frequent in ET, estimated at 0.3%-0.7% per year, possibly because of an acquired von Willebrand factorlike defect, and are often associated with the highest platelet counts. [2][3][4][5]12 Several studies have reported evidence of platelet activation in ET. 13,14 In particular, we reported previously enhanced urinary excretion of thromboxane (TX) metabolites in untreated ET patients.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4][5][6] However, up to 60% of ET patients experience a thrombotic event in their lifetimes, such as a transient ischemic attack, 2-8 myocardial infarction, or stroke. [2][3][4][5][6][7][8] Annual thrombotic event rates range from 2%-7% in ET patients treated with cytoreductive agents with or without coadministration of antiplatelet drugs, 2,4,[9][10][11] with estimates up to 13% in the absence of cytoreduction. 9 In the United Kingdom Medical Research Council Primary Thrombocythemia 1 study, the rate of a composite cardiovascular end point was approximately 2.8% per year in high-risk ET patients treated with hydroxyurea (HU) on a background of aspirin (98% of enrolled patients were on aspirin 75 mg daily).…”

Section: Introductionmentioning

confidence: 99%

“…Its prevalence is calculated to be approximately 20 of 100 000 people, 1 with estimates likely to increase in the near future because of the continuous rise of occasional asymptomatic diagnoses. [2][3][4] ET usually occurs in 50-to 60-year-old patients and has a longer life expectancy and a lower leukemic transformation rate compared with other myeloproliferative neoplasms. [2][3][4][5][6] However, up to 60% of ET patients experience a thrombotic event in their lifetimes, such as a transient ischemic attack, 2-8 myocardial infarction, or stroke.…”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4] ET usually occurs in 50-to 60-year-old patients and has a longer life expectancy and a lower leukemic transformation rate compared with other myeloproliferative neoplasms. [2][3][4][5][6] However, up to 60% of ET patients experience a thrombotic event in their lifetimes, such as a transient ischemic attack, 2-8 myocardial infarction, or stroke. [2][3][4][5][6][7][8] Annual thrombotic event rates range from 2%-7% in ET patients treated with cytoreductive agents with or without coadministration of antiplatelet drugs, 2,4,[9][10][11] with estimates up to 13% in the absence of cytoreduction.…”

Section: Introductionmentioning

confidence: 99%

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Aspirin-insensitive thromboxane biosynthesis in essential thrombocythemia is explained by accelerated renewal of the drug target

Pascale

Petrucci

Dragani

et al. 2012

Blood

190

210

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Essential thrombocythemia (ET) is characterized by enhanced platelet generation and thrombotic complications. Oncedaily low-dose aspirin incompletely inhibits platelet thromboxane A 2 (TXA 2 ) in the majority of ET patients. In the present study, we investigated the determinants of aspirin-insensitive platelet TXA 2 biosynthesis and whether it could be further suppressed by changing the aspirin dose, formulation, or dosing interval. In 41 aspirin-treated ET patients, the immature platelet count predicted serum TXB 2 independently of platelet count, age, JAK-2 V617F mutation, or cytoreduction (␤ ‫؍‬ 3.53, P ‫؍‬ .001). Twenty-one aspirintreated patients with serum TXB 2 > 4 ng/mL at 24 hours after dosing were randomized to the following 7-day regimens in a crossover design: enteric-coated aspirin 100 mg twice daily, enteric-coated aspirin 200 mg once daily, or plain aspirin 100 mg once daily. A twice-daily regimen caused a further 88% median (IQR, 78%-92%, P < .001) TXB 2 reduction and normalized the functional platelet response to aspirin, as assessed by urinary 11-dehydro-TXB 2 excretion and the VerifyNow Aspirin assay. Doubling the aspirin dose reduced serum TXB 2 only partially by 39% median (IQR, 29%-54%, P < .05). We conclude that the abnormal megakaryopoiesis characterizing ET accounts for a shorterlasting antiplatelet effect of low-dose aspirin through faster renewal of platelet cyclooxygenase-1, and impaired platelet inhibition can be rescued by modulating the aspirin dosing interval rather than the dose. (Blood. 2012;119(15):3595-3603)

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Aspirin-insensitive thromboxane biosynthesis in essential thrombocythemia is explained by accelerated renewal of the drug target

Pascale

Petrucci

Dragani

et al. 2012

Blood

190

210

View full text Add to dashboard Cite

show abstract

“…[2] An episode of arterial thrombosis may complicate the course of disease in 30-40% of cases. [4] Petrides and Siegel [5] reported that thrombosis clinically presents with an incidence of 6.6% per patient in a year. Moreover, a significant increase in the risk of thromobosis and mortality occurs with patients who have a history of previous thrombotic events and who are older than 60 years of age.…”

Section: Discussionmentioning

confidence: 99%