{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:48:47Z","timestamp":1773665327460,"version":"3.50.1"},"reference-count":24,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Haematol"],"published-print":{"date-parts":[[2013]]},"abstract":"<b><i>Background:<\/i><\/b> Patients with myeloproliferative neoplasms (MPN) have an increased risk for thrombosis and bleeding and show a defect in adenosine diphosphate (ADP)-induced platelet aggregation. This risk of thrombosis is further increased in MPN patients bearing the <i>JAK2<\/i>V617F mutation. Two ADP receptors, P2Y<sub>1<\/sub> and P2Y<sub>12<\/sub>, are present on platelets. Although the pattern of defective ADP-induced platelet aggregation in MPN suggests an abnormality in the P2Y<sub>12<\/sub> pathway, no previous studies have specifically evaluated P2Y<sub>12<\/sub> function in MPN or the relationship between P2Y<sub>12<\/sub> function and the <i>JAK2<\/i>V617F mutation. <b><i>Methods:<\/i><\/b> Forty-one MPN patients were enrolled, including 24 with essential thrombocythemia (ET), 16 with polycythemia vera (PV) and 1 with primary myelofibrosis. Platelet P2Y<sub>12<\/sub> function in MPN was evaluated by flow-cytometric measurement of the phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Clinical data were collected by review of medical records. <i>JAK2<\/i>V617F mutation was detected by allele-specific polymerase chain reaction. <i>JAK2<\/i>V617F allele burden was measured by the pyrosequencing method. <b><i>Results:<\/i><\/b> In patients with MPN, platelet P2Y<sub>12<\/sub> function determined by VASP platelet reactivity index (PRI) was inversely correlated with platelet and white blood cell (WBC) counts. In subgroup analysis, PRI was inversely correlated with platelet and WBC counts in PV. PRI was also inversely correlated with platelet counts in ET, but the correlation of PRI and WBC counts did not reach statistical significance. Eight of the 41 patients had a history of thrombosis and only 2 had a bleeding history. Neither thrombosis nor bleeding patients were found to have significantly different PRIs. <i>JAK2<\/i>V617F mutation data were available in 35 cases. PRI was not different between<i> JAK2<\/i>V617F mutation and wild-type patients but PRI had a trend towards an inverse correlation with <i>JAK2<\/i>V617F allele burden for patients with mutations. <b><i>Conclusions:<\/i><\/b> The present study provides the first explicit demonstration of a defect in the P2Y<sub>12<\/sub> pathway in platelets of patients with MPN. Furthermore, platelet P2Y<sub>12<\/sub> function, assayed by VASP, is inversely correlated with platelet and WBC counts in patients with MPN. Platelet P2Y<sub>12<\/sub> function also appears to be inversely correlated with <i>JAK2<\/i>V617F allele burden. This compromised P2Y<sub>12<\/sub> function may be a novel mechanism for the bleeding tendency associated with extreme thrombocytosis in MPN.<\/jats:p>","DOI":"10.1159\/000348413","type":"journal-article","created":{"date-parts":[[2013,6,10]],"date-time":"2013-06-10T14:57:01Z","timestamp":1370876221000},"page":"181-187","source":"Crossref","is-referenced-by-count":4,"title":["Clinical and Laboratory Significance of Defective P2Y<sub>12<\/sub> Pathway Function in Patients with Myeloproliferative Neoplasms: A Pilot Study"],"prefix":"10.1159","volume":"130","author":[{"given":"Hung","family":"Chang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee-Yung","family":"Shih","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan 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