Semin Thromb Hemost 2009; 35(1): 060-075
DOI: 10.1055/s-0029-1214149
© Thieme Medical Publishers

Toward a New Paradigm for the Identification and Functional Characterization of von Willebrand Disease

Emmanuel J. Favaloro1
  • 1Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, SWAHS, Westmead, Australia
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Publikationsverlauf

Publikationsdatum:
23. März 2009 (online)

ABSTRACT

The diagnosis and functional characterization of von Willebrand disease (VWD) is challenging. There are inherent difficulties in both its identification and classification because of clinical uncertainty, the limitations in the test processes and test panels typically used by laboratories, and because the classification scheme does not always allow unequivocal assignment of any subtype. This article reviews current thoughts and alternatives to the classic approach of the classification and functional characterization of VWD. Of particular interest to this author is the utility of an extended core test panel that includes additional functional VWF assays, such as the collagen binding assay, and the potential for desmopressin (DDAVP) challenge to not only provide therapeutic information but also assist in the better characterization of individuals with defects or deficiencies in von Willebrand factor (VWF). The potential use of supplementary assays such as the PFA-100 and the VWF propeptide assay after DDAVP challenge is also worth noting.

REFERENCES

  • 1 Sadler J E, Budde U, Eikenboom J CJ and the 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 2103-2114
  • 2 Favaloro E J. Laboratory identification of von Willebrand disease: technical and scientific perspectives.  Semin Thromb Hemost. 2006;  32 456-471
  • 3 Favaloro E J. An update on the von Willebrand factor collagen binding (VWF:CB) assay: 21 years of age and beyond adolescence, but not yet a mature adult.  Semin Thromb Hemost. 2007;  33 727-744
  • 4 Favaloro E J, Bonar R, Meiring M, Street A, Marsden K (on behalf of the RCPA QAP in Haematology). 2B or not 2B? Disparate discrimination of functional VWF discordance using different assay panels or methodologies may lead to success or failure in the early identification of type 2B VWD.  Thromb Haemost. 2007;  98 346-358
  • 5 James P, Lillicrap D. The role of molecular genetics in diagnosing von Willebrand disease.  Semin Thromb Hemost. 2008;  34 502-508
  • 6 Favaloro E J, Bonar R, Marsden K. on behalf of the RCPA QAP Haemostasis Committee . Lower limit of assay sensitivity: an under-recognised and significant problem in von Willebrand disease identification and classification.  Clin Lab Sci. 2008;  21 178-185
  • 7 Favaloro E J, Lippi G, Adcock D M. Preanalytical and postanalytical variables: the leading causes of diagnostic error in hemostasis?.  Semin Thromb Hemost. 2008;  34 612-634
  • 8 Duncan E M, Bonar R, Rodgers S E, Favaloro E J, Marsden K. RCPA QAP in Haematology, Haemostasis Committee. Methodology and outcomes of platelet aggregation testing in Australia, New Zealand and the Asia-Pacific region: results of a survey from the Royal College of Pathologists of Australasia Haematology Quality Assurance Program.  Int J Lab Hematol. 2008;  , March 21 (Epub ahead of print)
  • 9 Favaloro E J. Phenotypic identification of platelet type-von Willebrand disease and its discrimination from type 2B von Willebrand disease: a question of 2B or not 2B? A story of nonidentical twins? Or two sides of a multidenominational or multifaceted primary hemostasis coin?.  Semin Thromb Hemost. 2008;  34 113-127
  • 10 Othman M, Favaloro E J. Genetics of type 2B von Willebrand disease: “true 2B,” “tricky 2B,” or “not 2B.” What are the modifiers of the phenotype?.  Semin Thromb Hemost. 2008;  34 520-531
  • 11 Favaloro E J, Bonar R, Kershaw G , et al. Reducing errors in identification of von Willebrand disease: the experience of the Royal College of Pathologists of Australasia Quality Assurance Program.  Semin Thromb Hemost. 2006;  32 505-513
  • 12 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;  109 112-121
  • 13 James P D, Paterson A D, Notley C and Association of Hemophilia Clinic Directors of Canada et al. Genetic linkage and association analysis in type 1 von Willebrand disease: results from the Canadian type 1 VWD study.  J Thromb Haemost. 2006;  4 783-792
  • 14 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;  109 145-154
  • 15 Cumming A, Grundy P, Keeney S et al.. The UK Haemophilia Centre Doctors' Organisation. 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
  • 16 Penas N, Pérez-Rodríguez A, Torea J H et al.. 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
  • 17 Riddell A F, Jenkins P V, Nitu-Whalley I C, McCraw A H, Lee C A, Brown S A. 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
  • 18 James P D, Notley C, Hegadorn C et al.. Challenges in defining type 2M von Willebrand disease: results from a Canadian cohort study.  J Thromb Haemost. 2007;  5 1914-1922
  • 19 Meijer P, Haverkate F. An external quality assessment program for von Willebrand factor laboratory analysis: an overview from the European Concerted Action on Thrombosis and Disabilities Foundation.  Semin Thromb Hemost. 2006;  32 485-491
  • 20 Kitchen S, Jennings I, Woods T A, Kitchen D P, Walker I D, Preston F E. Laboratory tests for measurement of von Willebrand factor show poor agreement among different centers: results from the United Kingdom National External Quality Assessment Scheme for Blood Coagulation.  Semin Thromb Hemost. 2006;  32 492-498
  • 21 Hayes T E, Brandt J T, Chandler W L et al.. External peer review quality assurance testing in von Willebrand disease: the recent experience of the United States College of American Pathologists proficiency testing program.  Semin Thromb Hemost. 2006;  32 499-504
  • 22 Favaloro E J. 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) – a rebuttal.  J Thromb Haemost. 2008;  6 1999-2001
  • 23 Laffan M, Brown S A, Collins P W et al.. The diagnosis of von Willebrand disease: a guideline from the UK Haemophilia Centre Doctors' Organization.  Haemophilia. 2004;  10 199-217
  • 24 Adcock D M, Bethel M, Valcour A. Diagnosing von Willebrand disease: a large reference laboratory's perspective.  Semin Thromb Hemost. 2006;  32 472-479
  • 25 Meiring M, Badenhorst P N, Kelderman M. Performance and utility of a cost-effective collagen-binding assay for the laboratory diagnosis of von Willebrand disease.  Clin Chem Lab Med. 2007;  45 1068-1072
  • 26 Favaloro E J, Thom J, Patterson D et al.. Desmopressin therapy to assist the functional identification and characterisation of von Willebrand disease: differential utility from combining two (VWF:CB and VWF:RCo) von Willebrand factor activity assays?.  Thromb Res. 2008;  , December 7 (Epub ahead of print)
  • 27 Favaloro E J, Dean M, Grispo L, Exner T, von Koutts J. Willebrand's disease: use of collagen binding assay provides potential improvement to laboratory monitoring of desmopressin (DDAVP) therapy.  Am J Hematol. 1994;  45 205-211
  • 28 Michiels J J, van de Velde A, van Vliet H H, van der Planken M, Schroyens W, Berneman Z. Response of von Willebrand factor parameters to desmopressin in patients with type 1 and type 2 congenital von Willebrand disease: diagnostic and therapeutic implications.  Semin Thromb Hemost. 2002;  28 111-132
  • 29 Michiels J J, Berneman Z, Gadisseur A et al.. Characterization of recessive severe type 1 and 3 von Willebrand disease (VWD), asymptomatic heterozygous carriers versus bloodgroup O-related von Willebrand factor deficiency, and dominant type 1 VWD.  Clin Appl Thromb Hemost. 2006;  12 277-295
  • 30 Michiels J J, van Vliet H H, Berneman Z et al.. Intravenous DDAVP and factor VIII-von Willebrand factor concentrate for the treatment and prophylaxis of bleedings in patients with von Willebrand disease type 1, 2 and 3.  Clin Appl Thromb Hemost. 2007;  13 14-34
  • 31 Nichols W L, Hultin M B, James A H et al.. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA).  Haemophilia. 2008;  14 171-232
  • 32 Federici A B, Mazurier C, Berntorp E et al.. 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
  • 33 Pasi K J, Collins P W, Keeling D M et al.. Management of von Willebrand disease: a guideline from the UK Haemophilia Centre Doctors' Organization.  Haemophilia. 2004;  10 218-231
  • 34 Federici A B, Castaman G, Mannucci P M. Italian Association of Hemophilia Centers (AICE) . Guidelines for the diagnosis and management of von Willebrand disease in Italy.  Haemophilia. 2002;  8 607-621
  • 35 Favaloro E J, Kershaw G, Bukuya M, Hertzberg M, Koutts J. Laboratory diagnosis of von Willebrand disorder (VWD) and monitoring of DDAVP therapy: efficacy of the PFA-100® and VWF:CBA as combined diagnostic strategies.  Haemophilia. 2001;  7 180-189
  • 36 Favaloro E J. The utility of the PFA-100 in identification of von Willebrand disease: a concise review.  Semin Thromb Hemost. 2006;  32 537-545
  • 37 Favaloro E J. Laboratory monitoring of therapy in von Willebrand disease: efficacy of the PFA-100® and VWF:CB as coupled strategies.  Semin Thromb Hemost. 2006;  32 566-576
  • 38 Favaloro E J. Clinical utility of the PFA-100.  Semin Thromb Hemost. 2008;  34 709-733
  • 39 van Vliet H HDM, Kappers-Klunne M C, Leebeek F WG et al.. PFA-100 monitoring of von Willebrand factor (VWF) responses to DDAVP and FVIII/VWF concentrate substitution in von Willebrand disease type 1 and 2.  Thromb Haemost. 2008;  100 462-468
  • 40 Favaloro E J. A better approach to monitoring of therapy in von Willebrand disease?.  Thromb Haemost. 2008;  100 371-373
  • 41 Borchiellini A, Fijnvandraat K, ten Cate J W et al.. Quantitative analysis of von Willebrand factor propeptide release in vivo: effect of experimental endotoxemia and administration of 1-deamino-8-D-arginine vasopressin in humans.  Blood. 1996;  88 2951-2958
  • 42 Sztukowska M, Gallinaro L, Cattini M G et al.. Von Willebrand factor propeptide makes it easy to identify the shorter von Willebrand factor survival in patients with type 1 and type Vicenza von Willebrand disease.  Br J Haematol. 2008;  143 107-114
  • 43 Schooten C J, Tjernberg P, Westein E et al.. Cysteine-mutations in von Willebrand factor associated with increased clearance.  J Thromb Haemost. 2005;  3 2228-2237
  • 44 Haberichter S L, Balisteri M, Christopherson P et al.. Assay of the von Willebrand factor (VWF) propeptide to identify type I von Willebrand disease patients with decreased VWF survival.  Blood. 2006;  108 3344-3351
  • 45 Casonato A, Pontara E, Sartorello F et al.. Reduced von Willebrand factor survival in type Vicenza von Willebrand disease.  Blood. 2002;  99 180-184
  • 46 Haberichter S L, Castaman G, Budde U et al.. Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: molecular and clinical markers for the diagnosis and management of type 1 VWD (MCMDM-1VWD).  Blood. 2008;  111 4979-4985
  • 47 Millar C M, Riddell A F, Brown S A et al.. Survival of von Willebrand factor released following DDAVP in a type 1 von Willebrand disease cohort: influence of glycosylation, proteolysis and gene mutations.  Thromb Haemost. 2008;  99 916-924
  • 48 Gallinaro L, Cattini M G, Sztukowska M et al.. A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor.  Blood. 2008;  111 3540-3545
  • 49 Koutts J. A short history of diagnostic tests for von Willebrand disease: in memory of Barry Firkin (1930 to 2001) and Ted Zimmerman (1937 to 1988).  Semin Thromb Hemost. 2006;  32 445-455

Emmanuel J FavaloroPh.D. M.A.I.M.S. 

Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital

SWAHS, Westmead, NSW, 2145, Australia

eMail: emmanuel.favaloro@swahs.health.nsw.gov.au