Download PDF
Semin Thromb Hemost 2022; 48(06): 739-749
DOI: 10.1055/s-0042-1754354
Review Article

How Do Laboratories Perform von Willebrand Disease Diagnostics and Classification of von Willebrand Disease Patients? Results from External Quality Data and an International Survey

Martine J. Hollestelle
1   External Quality Control for Assays and Tests (ECAT) Foundation, Voorschoten, the Netherlands
,
Joost C. M. Meijers
2   Department of Experimental Vascular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
3   Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands
,
Piet Meijer
1   External Quality Control for Assays and Tests (ECAT) Foundation, Voorschoten, the Netherlands
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

Background Reduced or dysfunctional von Willebrand factor (VWF) may lead to von Willebrand disease (VWD), which is a common inherited bleeding disorder. VWD is classified into three major types: type 1 is a partial quantitative deficiency of VWF, type 3 is a complete quantitative deficiency of VWF, and type 2 consists of qualitative abnormalities of VWF. To arrive at a correct VWD diagnosis, multiple tests and a correct interpretation of these tests are needed.

Aim The aim of the present study was to gain insight into the approach of laboratories toward VWD diagnosis.

Methods Data from four samples of the external quality assessment (EQA) VWF surveys of the ECAT (External Quality Control for Assays and Tests) were evaluated. Furthermore, results were analyzed of a questionnaire that was sent to hemostasis laboratories about VWD diagnostic approaches.

Results For most EQA samples, the majority of participants indicated the correct classification. However, 6 to 60% indicated another classification. For all samples, significant differences in VWF results were observed between the correct and incorrect classifications. The questionnaire demonstrated that the testing approach varied between the laboratories, especially for parameters that were essential for discrimination between VWD type 1 and healthy individuals, as well as the cutoff values used to discriminate VWD types 1 and 2.

Conclusions Diagnosis of VWD is heterogeneous in diagnostic approach, guidelines, and cutoff values within large ranges of VWF results between laboratories. Harmonization of approaches and increased accuracy of VWF measurements may help to establish a correct diagnosis.

Keywords

von Willebrand disease - laboratory - external quality assessment

Supplementary Material



Publication History

Article published online:
02 September 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Sadler JE, Mannucci PM, Berntorp E. et al. Impact, diagnosis and treatment of von Willebrand disease. Thromb Haemost 2000; 84 (02) 160-174
    Google Scholar
  • 2 James PD, Connell NT, Ameer B. et al. ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease. Blood Adv 2021; 5 (01) 280-300
    Google Scholar
  • 3 Sadler JE, Budde U, Eikenboom JC. et al; Working Party on von Willebrand Disease Classification. 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
    Google Scholar
  • 4 Sadler JE, Rodeghiero F. ISTH SSC Subcommittee on von Willebrand Factor. Provisional criteria for the diagnosis of VWD type 1. J Thromb Haemost 2005; 3 (04) 775-777
    Google Scholar
  • 5 Nichols WL, Rick ME, Ortel TL. et al. Clinical and laboratory diagnosis of von Willebrand disease: a synopsis of the 2008 NHLBI/NIH guidelines. Am J Hematol 2009; 84 (06) 366-370
    Google Scholar
  • 6 Laffan MA, Lester W, O'Donnell JS. et al. The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology. Br J Haematol 2014; 167 (04) 453-465
    Google Scholar
  • 7 Favaloro EJ, Pasalic L, Curnow J. Laboratory tests used to help diagnose von Willebrand disease: an update. Pathology 2016; 48 (04) 303-318
    Google Scholar
  • 8 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 (05) 485-491
    Google Scholar
  • 9 Chandler WL, Peerschke EI, Castellone DD, Meijer P. NASCOLA Proficiency Testing Committee. Von Willebrand factor assay proficiency testing. The North American Specialized Coagulation Laboratory Association experience. Am J Clin Pathol 2011; 135 (06) 862-869
    Google Scholar
  • 10 Favaloro EJ, Dean E, Arunachalam S, Vong R, Mohammed S. Evaluating errors in the laboratory identification of von Willebrand disease using contemporary von Willebrand factor assays. Pathology 2022; 54 (03) 308-317
    Google Scholar
  • 11 Kitchen S, Jennings I, Woods TA, Kitchen DP, Walker ID, Preston FE. 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 (05) 492-498
    Google Scholar
  • 12 Hayes TE, Brandt JT, Chandler WL. 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 (05) 499-504
    Google Scholar
  • 13 Favaloro EJ, Bonar RA, Meiring M. et al. Evaluating errors in the laboratory identification of von Willebrand disease in the real world. Thromb Res 2014; 134 (02) 393-403
    Google Scholar
  • 14 ISO13528:2015. Statistical methods for use in proficiency testing by interlaboratory comparisons.
    Google Scholar
  • 15 Nichols WL, Hultin MB, James AH. 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 (02) 171-232
    Google Scholar
  • 16 Gill JC, Endres-Brooks J, Bauer PJ, Marks Jr WJ, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69 (06) 1691-1695
    Google Scholar
  • 17 Makris M, Hermans C. The 2021 von Willebrand disease guidelines: clarity and controversy. Haemophilia 2022; 28 (01) 1-3
    Google Scholar
  • 18 Othman M, Favaloro EJ. 2B von Willebrand disease diagnosis: considerations reflecting on 2021 multisociety guidelines. Res Pract Thromb Haemost 2021; 5 (08) e12635
    Google Scholar
  • 19 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the full-term infant. Blood 1987; 70 (01) 165-172
    Google Scholar
  • 20 Kalot MA, Husainat N, El Alayli A. et al. von Willebrand factor levels in the diagnosis of von Willebrand disease: a systematic review and meta-analysis. Blood Adv 2022; 6 (01) 62-71
    Google Scholar
  • 21 van Mourik JA, Boertjes R, Huisveld IA. et al. von Willebrand factor propeptide in vascular disorders: a tool to distinguish between acute and chronic endothelial cell perturbation. Blood 1999; 94 (01) 179-185
    Google Scholar
  • 22 Doshi BS, Rogers RS, Whitworth HB. et al. Utility of repeat testing in the evaluation for von Willebrand disease in pediatric patients. J Thromb Haemost 2019; 17 (11) 1838-1847
    Google Scholar
  • 23 Rodeghiero F, Tosetto A, Abshire T. et al; ISTH/SSC joint VWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost 2010; 8 (09) 2063-2065
    Google Scholar