Clearance of circulating activated platelets in polycythemia vera and essential thrombocythemia

Norma Maugeri, Simona Malato, Eti A. Femia, Mariateresa Pugliano, Lara Campana, Francesca Lunghi, Patrizia Rovere-Querini, Federico Lussana, GianMarco Podda, Marco Cattaneo, Fabio Ciceri, Angelo A. Manfredi

Research output: Contribution to journalArticle

Abstract

Essential thrombocythemia (ET) and polycythemia vera (PV) are characterized by persistent platelet activation. The mechanisms involved in their clearance are poorly characterized. In the present study, we report that leukocytes were actively involved in platelet disposal in 51 patients with ET and 30 with PV, but not in 70 age- and sex-matched controls. The fraction of circulating neutrophils and monocytes that had phagocytosed platelets, as assessed by flow cytometry, was significantly higher in patients with PV or ET, independently of hydroxyurea treatment, than in controls. Platelet phagocytosis by circulating leukocytes was confirmed by confocal and electron microscopy. The lack of effect of hydroxyurea, which disrupts the P-selectin/ P-selectin glycoprotein ligand 1 (PSGL-1) interaction, suggests a P-selectin-independent mechanism. This hypothesis was confirmed in an ad hoc animal model based on the in vivo injection of activated platelets from P-selectin +/+ and P-selectin -/- mice. P-selectin expression was associated with an earlier and effective clearance of platelets by neutrophils. A second delayed, P-selectin-independent phase actively involved monocytes. Our results suggest that phagocytic clearance of platelets by leukocytes occurs in PV and ET, possibly involving P-selectin-dependent and -independent pathways, thus representing a novel mechanism to remove activated platelets from the circulation.

Original languageEnglish
Pages (from-to)3359-3366
Number of pages8
JournalBlood
Volume118
Issue number12
DOIs
Publication statusPublished - Sep 22 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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  • Cite this

    Maugeri, N., Malato, S., Femia, E. A., Pugliano, M., Campana, L., Lunghi, F., Rovere-Querini, P., Lussana, F., Podda, G., Cattaneo, M., Ciceri, F., & Manfredi, A. A. (2011). Clearance of circulating activated platelets in polycythemia vera and essential thrombocythemia. Blood, 118(12), 3359-3366. https://doi.org/10.1182/blood-2011-02-337337