von Willebrand disease (VWD) type 2M is a distinct entity and clearly differs from type 1. The genotype-phenotype correlation for cases with ristocetin cofactor activity (RCo)/antigen (Ag) ratios <0.60 is clear, whereas the von Willebrand factor (VWF):collagen binding (CB)/VWF:Ag ratio is normal in VWD 2M. Typical laboratory features of VWD type 2 M are decreased ristocetin-induced platelet aggregation in the presence of a normal or near normal VWF multimeric pattern on a low-resolution agarose gel, a poor response to desmopressin (DDAVP) of VWF:RCo, and a good response of both VWF:CB and VWF:Ag to DDAVP. The phenotypic definition of VWD type 2M may need to be more stringent and should be the subject of an international standardization initiative.

Keywords:
Desmopressin response, Multimeric patterns, Phenotype, Platelet adhesion, Type 2M, von Willebrand disease
1.
Ruggeri ZM: The role of von Willebrand factor and fibrinogen in the initiation of platelet adhesion to thrombogenic surfaces. Thromb Haemost 1995;74:460–463.
2.
Sadler JE, Budde U, Eikenboom JC, Favaloro EJ, Hill FG, Holmberg L, Ingerslev J, Lee CA, Lillicrap D, Mannucci PM, Mazurier C, Meyer D, Nichols WL, Nishino M, Peake IR, Rodeghiero F, Schneppenheim R, Ruggeri ZM, Srivastava A, Montgomery RR, Federici AB: Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost 2006;4:2103–2114.
3.
Meyer D, Fressinaud E, Hilbert L, Ribba AS, Lavergne JM, Mazurier C: Type 2 von Willebrand disease causing defective von Willebrand factor-dependent platelet function. Best Pract Res Clin Haematol 2001;14:349–364.
4.
Lillicrap D: Von Willebrand disease – phenotype versus genotype: deficiency versus disease. Thromb Res 2007;120(suppl 1):S11–S16.
5.
Ribba AS, Loisel I, Lavergne JM, Juhan-Vague I, Obert B, Cherel G, Meyer D, Girma JP: Ser968Thr mutation within the A3 domain of von Willebrand factor (VWF) in two related patients leads to a defective binding of VWF to collagen. Thromb Haemost 2001;86:848–854.
6.
James PD, Notley C, Hegadorn C, Leggo J, Tuttle A, Tinlin S, Brown C, Andrews C, Labelle A, Chirinian Y, O’Brien L, Othman M, Rivard G, Rapson D, Hough C, Lillicrap D: The mutational spectrum of type 1 von Willebrand disease: results from a Canadian cohort study. Blood 2007;109:145–154.
7.
Goudemand J, Schneppenheim R, Budde U, Ingerslev J, Habart D, Vorlova Z, Holmberg L, Lethagen S, Pasi J, Hill F, Hashemi SM, Baronciani L, Hallden C, Guilliatt A, Lester W, Peake I: Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD). Blood 2007;109:112–121.
8.
Cumming A, Grundy P, Keeney S, Lester W, Enayat S, Guilliatt A, Bowen D, Pasi J, Keeling D, Hill F, Bolton-Maggs PH, Hay C, Collins P: An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease. Thromb Haemost 2006;96:630–641.
9.
Nitu-Whalley IC, Riddell A, Lee CA, Pasi KJ, Owens D, Enayat MS, Perkins SJ, Jenkins PV: Identification of type 2 von Willebrand disease in previously diagnosed type 1 patients: a reappraisal using phenotypes, genotypes and molecular modelling. Thromb Haemost 2000;84:998–1004.
10.
Penas N, Perez-Rodriguez A, Torea JH, Loures E, Noya MS, Lopez-Fernandez MF, Batlle J: von Willebrand disease R1374C: type 2A or 2M? A challenge to the revised classification. High frequency in the northwest of Spain (Galicia). Am J Hematol 2005;80:188–196.
11.
University of Sheffield: ISTH SSC VWF Database. http://www.vwf.group.shef.ac.uk/index.html
12.
Hilbert L, Gaucher C, Mazurier C: Identification of two mutations (Arg611Cys and Arg611His) in the A1 loop of von Willebrand factor (vWF) responsible for type 2 von Willebrand disease with decreased platelet-dependent function of vWF. Blood 1995;86:1010–1018.
13.
Casonato A, Pontara E, Sartorello F, Bertomoro A, Durante C, Girolami A: Type 2M von Willebrand disease variant characterized by abnormal von Willebrand factor multimerization. J Lab Clin Med 2001;137:70–76.
14.
Lethagen S, Frick K, Isaksson C, Kristoffersson A-C, Holmberg L: Revised classification and treatment of von Willebrand disease. Thromb Haemost 1998;80:199–200.
15.
Hoyer LW, Rizza CR, Tuddenham GD, Carta CA, Armitage H, Rotblat F: von Willebrand factor multimer patterns in von Willebrand’s disease. Br J Haematol 1983;55:493–507.
16.
Schneppenheim R, Budde U, Ruggeri ZM: A molecular approach to the classification of von Willebrand disease (review). Best Pract Res Clin Haematol 2001;14:281–298.
17.
Michiels JJ, Berneman Z, Gadisseur A, van der Planken M, Schroyens W, van de Velde A, van Vliet H: Classification and characterization of hereditary types 2A, 2B, 2C, 2D, 2E, 2M, 2N, and 2U (unclassifiable) von Willebrand disease. Clin Appl Thromb Hemost 2006;12:397–420.
18.
Favaloro EJ: Collagen binding assay for von Willebrand factor (VWF:CBA): detection of von Willebrands disease (VWD), and discrimination of VWD subtypes, depends on collagen source. Thromb Haemost 2000;83:127–135.
19.
Riddell AF, Jenkins PV, Nitu-Whalley IC, McCraw AH, Lee CA, Brown SA: Use of the collagen-binding assay for von Willebrand factor in the analysis of type 2M von Willebrand disease: a comparison with the ristocetin cofactor assay. Br J Haematol 2002;116:187–192.
20.
Federici AB, Mazurier C, Berntorp E, Lee CA, Goudemand J, Lethagen S, Nitu I, Ludwig G, Hilbert L, Mannucci PM: Biologic response to desmopressin in patients with severe type 1 and type 2 von Willebrand disease: results of a multicenter European study. Blood 2004;103:2032–2038.
21.
Batlle J, Pérez-Rodríguez A, Franqueira MD, López-Fernández MF: Type 2M von Willebrand disease: a variant of type 2A? J Thromb Haemost 2008;6:388–390.
© 2009 S. Karger AG, Basel
2009
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.