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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2587-2595. Prepublished online as a Blood First Edition Paper on May 23, 2006; DOI 10.1182/blood-2006-03-009449. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-03-009449v1 108/8/2587    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 Nurden, P. Articles by Enouf, J. Search for Related Content PubMed PubMed Citation Articles by Nurden, P. Articles by Enouf, J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Impaired megakaryocytopoiesis in type 2B von Willebrand disease with severe thrombocytopenia Paquita Nurden, Najet Debili, William Vainchenker, Regis Bobe, Raymonde Bredoux, Elisabeth Corvazier, Robert Combrie, Edith Fressinaud, Dominique Meyer, Alan T. Nurden, and Jocelyne Enouf From the Centre de Référence des Pathologies Plaquettaires and Institut Fédératif de Recherche No. 4, Hôpital Cardiologique, Pessac; Institut National de la Santé et de la Recherche Médicale (INSERM) U.790, Villejuif; INSERM U.689, Hôpital Lariboisière, Paris; and INSERM U.710, Le Kremlin-Bicêtre, France. In type 2B von Willebrand disease, there is spontaneous binding of mutated von Willebrand factor (VWF) multimers to platelets. Here we report a family in which severe thrombocytopenia may also be linked to abnormal megakaryocytopoiesis. A heterozygous mutation in the VWF A1 domain gave a R1308P substitution in an interactive site for glycoprotein Ib (GPIb). Electron microscopy showed clusters of platelets in close contact. Binding of antibodies to the GPIb N-terminal domain was decreased, whereas GPIX and GPV were normally detected. In Western blotting (WB), GPIb, IIb, and 3 were normally present. Proteins involved in Ca2+ homeostasis were analyzed by quantitating platelet mRNA or by WB. Plasma membrane Ca2+ ATPase (PMCA)-4b and type III inositol trisphosphate receptor (InsP3-R3) were selectively increased. The presence of degradation products of polyadenosine diphosphate (ADP)-ribose polymerase protein (PARP) suggested ongoing caspase-3 activity. These were findings typical of immature normal megakaryocytes cultured from peripheral blood CD34+ cells with TPO. Significantly, megakaryocytes from the patients in culture produced self-associated and interwoven proplatelets. Immunolocalization showed VWF not only associated with platelets, but already on the megakaryocyte surface and within internal channels. In this family, type 2B VWD is clearly associated with abnormal platelet production. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Impaired megakaryocytopoiesis in type 2B von Willebrand disease Augusto B. Federici Blood 2006 108: 2498-2499. [Full Text] [PDF] This article has been cited by other articles: C. Strassel, A. Eckly, C. Leon, C. Petitjean, M. Freund, J.-P. Cazenave, C. Gachet, and F. Lanza Intrinsic impaired proplatelet formation and microtubule coil assembly of megakaryocytes in a mouse model of Bernard-Soulier syndrome Haematologica, June 1, 2009; 94(6): 800 - 810. [Abstract] [Full Text] [PDF] P. Nurden The VWD2B saga continues to Montreal Blood, April 2, 2009; 113(14): 3134 - 3135. [Full Text] [PDF] S. C. Jackson, G. D. Sinclair, S. Cloutier, Z. Duan, M. L. Rand, and M.-C. Poon The Montreal platelet syndrome kindred has type 2B von Willebrand disease with the VWF V1316M mutation Blood, April 2, 2009; 113(14): 3348 - 3351. [Abstract] [Full Text] [PDF] A. B. Federici, P. M. Mannucci, G. Castaman, L. Baronciani, P. Bucciarelli, M. T. Canciani, A. Pecci, P. J. Lenting, and P. G. De Groot Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B: a cohort study of 67 patients Blood, January 15, 2009; 113(3): 526 - 534. [Abstract] [Full Text] [PDF] C. Ghevaert, A. Salsmann, N. A. Watkins, E. Schaffner-Reckinger, A. Rankin, S. F. Garner, J. Stephens, G. A. Smith, N. Debili, W. Vainchenker, et al. A nonsynonymous SNP in the ITGB3 gene disrupts the conserved membrane-proximal cytoplasmic salt bridge in the {alpha}IIb{beta}3 integrin and cosegregates dominantly with abnormal proplatelet formation and macrothrombocytopenia Blood, April 1, 2008; 111(7): 3407 - 3414. [Abstract] [Full Text] [PDF] L. J. Suva, E. Hartman, J. D. Dilley, S. Russell, N. S. Akel, R. A. Skinner, W. R. Hogue, U. Budde, K. I. Varughese, T. Kanaji, et al. Platelet Dysfunction and a High Bone Mass Phenotype in a Murine Model of Platelet-Type von Willebrand Disease Am. J. Pathol., February 1, 2008; 172(2): 430 - 439. [Abstract] [Full Text] [PDF] A. T. Nurden and P. Nurden Inherited thrombocytopenias Haematologica, September 1, 2007; 92(9): 1158 - 1164. [Full Text] [PDF] A. T. Nurden ROCK and Rho(ll) in bone marrow Blood, July 1, 2007; 110(1): 5 - 6. [Full Text] [PDF]

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