External Quality Assessment Data for Investigation of von Willebrand Disease: Focus on Relative Utility of Contemporary Functional von Willebrand Factor Assays. The United Kingdom National External Quality Assessment Scheme (UK NEQAS) Experience

Abstract

Von Willebrand disease (VWD) is one of the most common hereditary bleeding disorders. Effective management of patients and their families depends on accurate diagnosis and subtype classification, and quality assurance including participation in proficiency testing programs is essential to ensure the accuracy of the panel of assays required to achieve this diagnosis. We report here findings from recent external quality assessment (EQA) exercises, as well as from a questionnaire about diagnostic practices employed by centers in the United Kingdom National Quality Assessment Scheme (UK NEQAS) performing von Willebrand factor (VWF) assays. Plasma samples from donors with VWD, “normal” donors, the International Society for Thrombosis and Haemostasis Scientific Subcommittee (ISTH SSC) plasma standard, and whole blood samples were sent to participants in the UK NEQAS BC program for VWF investigation. Calibration of lot#5 of the ISTH SSC plasma standard was shown to give improved comparability between the recovered value from an EQA exercise and the assigned potency for VWF activity assays. Diagnostic accuracy and precision amongst UK NEQAS participants was good, with an average 99% of centers reporting the correct interpretation for normal, type 1 and type 2 VWD samples, 100% diagnostic accuracy for centers performing FVIII binding assays, and good agreement amongst centers performing multimeric analysis. Genetic analysis of the VWF gene by specialist centers demonstrated errors in the genotyping process in one center, but also demonstrated failings in the interpretation of results in other centers. Despite evidence of good laboratory accuracy and precision in their assays, a questionnaire identified marked variation in diagnostic criteria employed, underlining the importance of guidelines to support the diagnosis of VWD.

Keywords

von Willebrand factor - functional assays - external quality assessment

Publication History

Article published online:
02 September 2022

• References

• 1 Connell NT, Flood VH, Brignardello-Petersen R. et al. ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease. Blood Adv 2021; 5 (01) 301-325
• 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
• 3 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
• 4 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
• 5 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
• 6 Favaloro EJ, Bonar R, Hollestelle MJ. et al. Differential sensitivity of von Willebrand factor activity assays to reduced VWF molecular weight forms: a large international cross-laboratory study. Thromb Res 2018; 166: 96-105
• 7 Favaloro EJ, Bonar R, Marsden K. Lower limit of assay sensitivity: an under-recognised and significant problem in von Willebrand disease identification and classification. Clin Lab Sci 2008; 21 (03) 178-183
• 8 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; Apr; 54 (03) 308-317
• 9 Abdulrehman J, Ziemba YC, Hsu P. et al. Diagnosis of von Willebrand disease: an assessment of the quality of testing in North American laboratories. Haemophilia 2021; 27 (06) e713-e720
• 10 Sharma R, Haberichter SL. New advances in the diagnosis of von Willebrand disease. Hematology (Am Soc Hematol Educ Program) 2019; 2019 (01) 596-600
• 11 Perry DJ, Cumming T, Goodeve A. et al. The UK National External Quality Assessment Scheme for heritable bleeding disorders. Semin Thromb Hemost 2014; 40 (02) 261-268
• 12 Jennings I, Kitchen DP, Woods TA, Kitchen S, Preston FE, Walker ID. Stability of coagulation proteins in lyophilized plasma. Int J Lab Hematol 2015; 37 (04) 495-502
• 13 Bodó I, Eikenboom J, Montgomery R, Patzke J, Schneppenheim R, Di Paola J. von Willebrand factor Subcommittee of the Standardization and Scientific Committee of the International Society for Thrombosis and Haemostasis. Platelet-dependent von Willebrand factor activity. Nomenclature and methodology: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13 (07) 1345-1350
• 14 Favaloro EJ. Commentary on the ASH ISTH NHF WFH 2021 guidelines on the diagnosis of VWD: reflections based on recent contemporary test data. Blood Adv 2022; 6 (02) 416-419