Thromb Haemost 2020; 120(10): 1442-1453
DOI: 10.1055/s-0040-1714351
Cellular Haemostasis and Platelets

Patients with Essential Thrombocythemia may be Poor Responders to Enteric-Coated Aspirin, but not to Plain Aspirin

Mariangela Scavone*
1  Laboratory of Hemostasis and Thrombosis, Dipartimento di Scienze della Salute, Università degli Studi di Milan, Milan, Lombardia, Italy
,
Jessica Rizzo*
2  Clinical Biochemistry and Mass Spectrometry, Dipartimento di Scienze della Salute, Università degli Studi di Milan, Milan, Lombardia, Italy
,
Eti A. Femia
1  Laboratory of Hemostasis and Thrombosis, Dipartimento di Scienze della Salute, Università degli Studi di Milan, Milan, Lombardia, Italy
,
Gian Marco Podda
1  Laboratory of Hemostasis and Thrombosis, Dipartimento di Scienze della Salute, Università degli Studi di Milan, Milan, Lombardia, Italy
3  Unità di Medicina, ASST Santi Paolo e Carlo, Ospedale San Paolo, Milan, Italy
,
Elena Bossi
1  Laboratory of Hemostasis and Thrombosis, Dipartimento di Scienze della Salute, Università degli Studi di Milan, Milan, Lombardia, Italy
,
Sabrina Caberlon
3  Unità di Medicina, ASST Santi Paolo e Carlo, Ospedale San Paolo, Milan, Italy
,
Rita Paroni
2  Clinical Biochemistry and Mass Spectrometry, Dipartimento di Scienze della Salute, Università degli Studi di Milan, Milan, Lombardia, Italy
,
Marco Cattaneo
1  Laboratory of Hemostasis and Thrombosis, Dipartimento di Scienze della Salute, Università degli Studi di Milan, Milan, Lombardia, Italy
3  Unità di Medicina, ASST Santi Paolo e Carlo, Ospedale San Paolo, Milan, Italy
› Author Affiliations
Funding The study was partially supported by grant PSR 2015–2017- Linea 2 by Dipartimento di Scienze della Salute - Università degli Studi di Milano, and by Fondazione Carlo Erba in collaboration with Kedrion Biopharma “Guelfo Marcucci-2017.” M.S. was supported by a Post-Doctoral Fellowship by Fondazione Umberto Veronesi (Post-Doctoral Fellowship).

Abstract

Essential thrombocythemia (ET) patients are treated with aspirin (acetylsalicylic acid [ASA]) to prevent thrombosis. Previous studies showed that serum thromboxane (Tx) B2 was high 24 hours after enteric-coated (EC)-ASA in ET patients, due to increased number of noninhibited reticulated platelets (RPs), consequent to high platelet turnover, and that ASA should be given twice a day to ET patients. We studied ET patients (n = 17) and healthy subjects (n = 10) on 100 mg EC-ASA once daily; experiments were repeated after 14-day treatment with 100 mg plain-ASA once daily. Serum TxB2, plasma ASA, and salicylic acid (SA) were measured before the morning dose and up to 8 hours thereafter. Blood activity of ASA-deacethylating esterases, in vitro inhibition of collagen-induced TxB2 production by ASA (10–1,000 µM), and number of RP were measured. TxB2 inhibition by ASA in vitro and esterases activities were normal in all subjects. EC-ASA elicited highly variable responses; 6 ET patients were poor responders, as their serum TxB2 was high after EC-ASA; their plasma levels of ASA and SA were low/undetectable. In contrast to EC-ASA, plain ASA decreased serum TxB2 and increased plasma ASA and SA in all subjects. Serum TxB2 was high in ET patients at 24 hours and significantly correlated with RP count (but not RP percentage) and platelet count. Plain ASA should be used in ET patients to inhibit platelets efficiently. The identification of ET patients who might benefit from twice a day ASA could simply be based on their platelet count: since their platelet turnover is not increased, ET patients with normalized platelet count should not need twice a day ASA treatment.

Authors' Contributions

M.S. and J.R. contributed to the design of the study, performed laboratory analyses, analyzed the data, and contributed to writing the manuscript and critically reviewed it; E.A.F. contributed to the design of the study, performed laboratory analyses, and critically reviewed the manuscript; G.M.P. and S.C. contributed to the design of the study, enrolled the patients, analyzed the data, and critically reviewed the manuscript; E.B. performed laboratory tests and critically reviewed the manuscript; R.P. contributed to the design of the study, set up the methods for measurement of ASA, SA, and esterase activity, supervised the activities of the clinical biochemistry laboratory, contributed to writing the manuscript, and reviewed it critically; M.C. designed the study, coordinated the group, contributed to data analysis and interpretation, and wrote the manuscript. All authors read and approved the final manuscript.


* M.S. and J.R. contributed equally to this study.




Publication History

Received: 24 May 2020

Accepted: 10 June 2020

Publication Date:
27 July 2020 (online)

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