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Blood, 15 January 2004, Vol. 103, No. 2, pp. 500-506. Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-01-0275. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0275v1 103/2/500    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Houwerzijl, E. J. Articles by de Wolf, J. Th. M. Search for Related Content PubMed PubMed Citation Articles by Houwerzijl, E. J. Articles by de Wolf, J. Th. M. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura Ewout J. Houwerzijl, Nel R. Blom, Johannes J. L. van der Want, Mariet T. Esselink, Jan J. Koornstra, Jan W. Smit, Henk Louwes, Edo Vellenga, and Joost Th. M. de Wolf From the Department of Hematology and Department of Medical Oncology, University Hospital Groningen, The Netherlands; Laboratory for Cell Biology and Electron Microscopy, University of Groningen, The Netherlands; and Department of Nuclear Medicine, Martini Hospital, Groningen, The Netherlands. To investigate whether altered megakaryocyte morphology contributes to reduced platelet production in idiopathic thrombocytopenic purpura (ITP), ultrastructural analysis of megakaryocytes was performed in 11 ITP patients. Ultrastructural abnormalities compatible with (para-)apoptosis were present in 78% ± 14% of ITP megakaryocytes, which could be reversed by in vivo treatment with prednisone and intravenous immunoglobulin. Immunohistochemistry of bone marrow biopsies of ITP patients with extensive apoptosis showed an increased number of megakaryocytes with activated caspase-3 compared with normal (28% ± 4% versus 0%). No difference, however, was observed in the number of bone marrow megakaryocyte colony-forming units (ITP, 118 ± 93/105 bone marrow cells; versus controls, 128 ± 101/105 bone marrow cells; P = .7). To demonstrate that circulating antibodies might affect megakaryocytes, suspension cultures of CD34+ cells were performed with ITP or normal plasma. Morphology compatible with (para-)apoptosis could be induced in cultured megakaryocytes with ITP plasma (2 of 10 samples positive for antiplatelet autoantibodies). Finally, the plasma glycocalicin index, a parameter of platelet and megakaryocyte destruction, was increased in ITP (57 ± 70 versus 0.7 ± 0.2; P = .009) and correlated with the proportion of megakaryocytes showing (para-) apoptotic ultrastructure (P = .02; r = 0.7). In conclusion, most ITP megakaryocytes show ultrastructural features of (para-) apoptosis, probably due to action of factors present in ITP plasma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. K. Kruit, A. L. Drayer, V. W. Bloks, N. Blom, S. G. Olthof, P. J. J. Sauer, G. de Haan, I. P. Kema, E. Vellenga, and F. Kuipers Plant Sterols Cause Macrothrombocytopenia in a Mouse Model of Sitosterolemia J. Biol. Chem., March 7, 2008; 283(10): 6281 - 6287. 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Houwerzijl, N. R. Blom, J. J. L. van der Want, H. Louwes, M. T. Esselink, J. W. Smit, E. Vellenga, and J. Th. M. de Wolf Increased peripheral platelet destruction and caspase-3-independent programmed cell death of bone marrow megakaryocytes in myelodysplastic patients Blood, May 1, 2005; 105(9): 3472 - 3479. [Abstract] [Full Text] [PDF] L. Centurione, A. Di Baldassarre, M. Zingariello, D. Bosco, V. Gatta, R. A. Rana, V. Langella, A. Di Virgilio, A. M. Vannucchi, and A. R. Migliaccio Increased and pathologic emperipolesis of neutrophils within megakaryocytes associated with marrow fibrosis in GATA-1low mice Blood, December 1, 2004; 104(12): 3573 - 3580. [Abstract] [Full Text] [PDF]

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