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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 14, 2006 Accepted April 12, 2006 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 Centre de Reference des Pathologies Plaquettaires,Institut Federatif de Recherche 4. Pessac, France Inserm U.790, Villejuif, France INSERM U.790, Villejuif, France Inserm U.689, Hopital Lariboisiere, Paris, France Inserm U.689, Hopital Lariboisiere, Paris, france CRPP, Institut Federatif de Recherche 4. Pessac, France Inserm U.143, Le Kremlin-Bicetre, France, Inserm U.143, Le Kremlin-Bicetre, France Inserm U.143, Le Kremlin-Bicetre, France Centre de Reference des Pathologies Plaquettaires, Institut Federatif de Recherche 4. Pessac, France * Corresponding author; email: paquita.nurden{at}cnrshl.u-bordeaux2.fr. In type 2B von Willebrand disease, there is spontaneous binding of mutated 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 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 megakaryoctes 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: P. Nurden, A. T Nurden, S. La Marca, M. Punzo, L. Baronciani, and A. B. Federici Platelet morphological changes in 2 patients with von Willebrand disease type 3 caused by large homozygous deletions of the von Willebrand factor gene Haematologica, November 1, 2009; 94(11): 1627 - 1629. [Full Text] [PDF] 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] S. Vettore, R. Scandellari, S. Moro, A. M. Lombardi, M. Scapin, M. L. Randi, and F. Fabris Novel point mutation in a leucine-rich repeat of the GPIb{alpha} chain of the platelet von Willebrand factor receptor, GPIb/IX/V, resulting in an inherited dominant form of Bernard-Soulier syndrome affecting two unrelated families: the N41H variant Haematologica, November 1, 2008; 93(11): 1743 - 1747. [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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