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Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-01-0275.
Submitted January 29, 2003
Accepted August 28, 2003
Ultrastructural study shows morphological 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 T M de Wolf*
Department of Hematology, University Hospital, Groningen, The Netherlands
Department of Medical Oncology, University Hospital, Groningen, The Netherlands
Laboratory for Cell Biology and Electron Microscopy, University of Groningen, Groningen, The Netherlands
Department of Nuclear Medicine, Martini Hospital, Groningen, The Netherlands
* Corresponding author; email: j.th.m.de.wolf{at}int.azg.nl.
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 to normal (28 ± 4% versus 0%). No difference, however, was observed in the number of bone marrow colony-forming units-megakaryocyte (ITP: 118 ± 93 versus controls: 128 ± 101; p=0.7). 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 (2/10 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=0.009) and correlated with the proportion of megakaryocytes showing (para-)apoptotic ultrastructure (p=0.02; r=0.7). In conclusion, the majority of ITP megakaryocytes show ultrastructural features of (para-)apoptosis, probably due to action of factors present in ITP plasma.
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