Semin Thromb Hemost 2011; 37(5): 470-479
DOI: 10.1055/s-0031-1281031
© Thieme Medical Publishers

The International Society on Thrombosis and Haematosis von Willebrand Disease Database: An Update

Daniel J. Hampshire1 , Anne C. Goodeve1 , 2
  • 1Haemostasis Research Group, Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom
  • 2Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom
Further Information

Publication History

Publication Date:
18 November 2011 (online)


The online locus-specific database for von Willebrand disease (VWFdb) acts as a repository for sequence variant data and associated resources for those with an interest in the disorder. It currently holds details of 561 mutations and 217 polymorphisms in the von Willebrand factor (VWF) gene. Lists can be queried and displayed by VWF region or disease type. A total of 42% of the mutations are located in the large exon 28, the most heavily studied VWF region, and mutations have been reported in all but 4 of the 51 protein-coding exons. Polymorphisms are reported in the 5′ and 3′ untranslated regions and in 33 exons and 35 introns. Additional resources include references linked to sequence variation entries, descriptors of each VWD type, genomic and cDNA sequences, nomenclature for VWF and its attributes, Human Genome Variation Society sequence variant nomenclature recommendations, multimer images, and related densitometry traces for type 2 VWD. Analysis of recessively inherited VWD indicates that whereas the majority (69%) of type 3 VWD patients are homozygous for their mutations, the majority (62%) of 2N patients are compound heterozygous. Comparison of missense substitutions reported as mutations with those reported as polymorphisms suggests that loss or gain of cysteine, tryptophan, methionine, or glutamate residues are more likely to result in a pathogenic effect than loss/gain of other VWF residues.


  • 1 Ginsburg D, Sadler J E. von Willebrand disease: a database of point mutations, insertions, and deletions. For the Consortium on von Willebrand Factor Mutations and Polymorphisms, and the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis.  Thromb Haemost. 1993;  69 (2) 177-184
  • 2 Ginsberg D, Sadler J E. von Willebrand Factor (VWF) Database. Available at: , using Accessed May 12, 2010
  • 3 VWFdb. International Society on Thrombosis and Haemostasis Scientific and Standardization Committee VWF Information home page. Available at: Accessed November 20, 2010
  • 4 Sadler J E, Budde U, Eikenboom J C Working Party on von Willebrand Disease Classification et al. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.  J Thromb Haemost. 2006;  4 (10) 2103-2114
  • 5 James P D, Notley C, Hegadorn C et al.. The mutational spectrum of type 1 von Willebrand disease: Results from a Canadian cohort study.  Blood. 2007;  109 (1) 145-154
  • 6 Goodeve A, Eikenboom J, Castaman G et al.. 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 (1) 112-121
  • 7 Cumming A, Grundy P, Keeney S UK Haemophilia Centre Doctors' Organisation et al. An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease.  Thromb Haemost. 2006;  96 (5) 630-641
  • 8 Othman M, Chirinian Y, Brown C et al.. Functional characterization of a 13-bp deletion (c.-1522_-1510del13) in the promoter of the von Willebrand factor gene in type 1 von Willebrand disease.  Blood. 2010;  116 (18) 3645-3652
  • 9 Schneppenheim R, Michiels J J, Obser T et al.. A cluster of mutations in the D3 domain of von Willebrand factor correlates with a distinct subgroup of von Willebrand disease: type 2A/IIE.  Blood. 2010;  115 (23) 4894-4901
  • 10 PT-VWD-Registry .Registry on platelet type von Willebrand disease. Available at: Accessed November 20, 2010
  • 11 Othman M, Lillicrap D. Distinguishing between non-identical twins: platelet type and type 2B von Willebrand disease.  Br J Haematol. 2007;  138 (5) 665-666
  • 12 Frontroth J P, Hepner M, Sciuccati G, Feliú Torres A, Pieroni G, Bonduel M. Prospective study of low-dose ristocetin-induced platelet aggregation to identify type 2B von Willebrand disease (VWD) and platelet-type VWD in children.  Thromb Haemost. 2010;  104 (6) 1158-1165
  • 13 Riddell A F, Gomez K, Millar C M et al.. Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.  Blood. 2009;  114 (16) 3489-3496
  • 14 Flood V H, Lederman C A, Wren J S et al.. Absent collagen binding in a VWF A3 domain mutant: utility of the VWF:CB in diagnosis of VWD.  J Thromb Haemost. 2010;  8 (6) 1431-1433
  • 15 Melo-Nava B M, Benítez H, Palacios J J et al.. Molecular study of VWF gene from Mexican mestizo patients with von Willebrand disease, and the finding of three new mutations.  Blood Cells Mol Dis. 2007;  39 (3) 361-365
  • 16 Ribba A S, Loisel I, Lavergne J M et al.. 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 (3) 848-854
  • 17 Hickson N, Hampshire D, Winship P MCMDM-1VWD and ZPMCB-VWD study groups et al. von Willebrand factor variant p.Arg924Gln marks an allele associated with reduced von Willebrand factor and factor VIII levels.  J Thromb Haemost. 2010;  8 (9) 1986-1993
  • 18 Budde U, Schneppenheim R, Eikenboom J et al.. Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD).  J Thromb Haemost. 2008;  6 (5) 762-771
  • 19 Bowen D J, Collins P W, Lester W UK Haemophilia Centre Doctors' Organization et al. The prevalence of the cysteine1584 variant of von Willebrand factor is increased in type 1 von Willebrand disease: co-segregation with increased susceptibility to ADAMTS13 proteolysis but not clinical phenotype.  Br J Haematol. 2005;  128 (6) 830-836
  • 20 O'Brien L A, James P D, Othman M Association of Hemophilia Clinic Directors of Canada et al. Founder von Willebrand factor haplotype associated with type 1 von Willebrand disease.  Blood. 2003;  102 (2) 549-557
  • 21 Kemball-Cook G. The Haemophilia A Mutation, Structure, Test and Resource Site (HAMSTeRS/HADB). Available at:. Accessed March 12, 2010
  • 22 Green P. Haemophilia B Mutation Database 2004. Available at: Accessed March 12, 2010
  • 23 Fokkema I F, den Dunnen J T, Taschner P E. LOVD: easy creation of a locus-specific sequence variation database using an “LSDB-in-a-box” approach.  Hum Mutat. 2005;  26 (2) 63-68
  • 24 HGVS .Nomenclature for the description of sequence variations. Available at: Accessed October 1, 2011
  • 25 Vidal D, Gallardo F. Hemobase. Available at: Accessed January 27, 2011
  • 26 Corrales I, Ramírez L, Altisent C, Parra R, Vidal F. Rapid molecular diagnosis of von Willebrand disease by direct sequencing. Detection of 12 novel putative mutations in VWF gene.  Thromb Haemost. 2009;  101 (3) 570-576

Anne GoodeveB.Sc. Ph.D. 

Head, Haemostasis Research Group, Department of Cardiovascular Science, Faculty of Medicine, Dentistry and Health

Beech Hill Road, Sheffield, S10 2RX, United Kingdom