Evaluating Performance of Contemporary and Historical von Willebrand Factor (VWF) Assays in the Laboratory Identification of von Willebrand Disease (VWD): The Australasian Experience

Emmanuel J. Favaloro; Elysse Dean; Sandya Arunachalam

doi:10.1055/s-0042-1753528

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2022; 48(06): 711-731
DOI: 10.1055/s-0042-1753528

Review Article

Evaluating Performance of Contemporary and Historical von Willebrand Factor (VWF) Assays in the Laboratory Identification of von Willebrand Disease (VWD): The Australasian Experience

Emmanuel J. Favaloro

¹Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, New South Wales, Australia

²Sydney Centers for Thrombosis and Haemostasis, Westmead, New South Wales Australia

³Faculty of Science and Health, Charles Sturt University, Wagga Wagga, New South Wales, Australia

,

Elysse Dean

⁴RCPAQAP Haematology, St Leonards, New South Wales, Australia

,

Sandya Arunachalam

⁴RCPAQAP Haematology, St Leonards, New South Wales, Australia

› Institutsangaben

Abstract

von Willebrand disease (VWD) is a common bleeding disorder that arises from deficiency and/or defects of von Willebrand factor (VWF). Appropriate diagnosis of VWD, including differential identification of qualitative (types 2A, 2B, 2M, 2N VWD) versus quantitative (types 1 and 3 VWD) defects remains problematic but has important management implications, given differential therapy. Complete assessment for VWD in a patient with a bleeding history requires comprehensive test panels, including VWF activity and antigen. We describe the Australasian experience, using data from the Royal College of Pathologists of Australasia (RCPA) Quality Assurance Program (QAP) related to VWF testing in their VWD test module. The RCPAQAP has been providing samples for VWF testing since 1998, representing 25 years of proficiency testing related to VWD diagnosis. A total of 109 samples have been dispatched to participants over these years, with current assessment involving dispatches of two samples (=4 samples) per year. Samples have represented all types of VWD, as well as normal or other samples, including acquired von Willebrand syndrome and plasma VWF concentrates as used in VWD therapy. Different VWF assays and activity/antigen ratios show different utility in VWD and type identification. In the past 9 years of data capture, a total of 166 errors were identified from a total of 1,839 interpretations, representing a base error rate of 9.0%. Identification errors were highest for type 2 VWD samples (15.3%), intermediate for type 1 VWD samples (7.5%), and lowest for normal samples (2.4%). Errors can be linked to assay limitations, including assay variability and low-level VWF detection limits, as well as laboratory issues (including test result misinterpretation, which accounts for approximately 40% of all errors for type 2 VWD). For test-associated errors, VWF:RCo and VWF:GPIbM were associated with the highest variability and error rate, which was up to 10x higher than that using VWF:CB. As a test group, chemiluminescence-based procedures were associated with lowest inter-laboratory variability, best low-level VWF detection (down to <1 U/dL), and least errors overall. These findings inform on reasons behind high rates of errors associated with VWD diagnosis, with some assays and methodologies performing substantially better than others.

Keywords

von Willebrand disease - diagnosis - exclusion - von Willebrand factor - laboratory testing - interpretation - external quality assessment - proficiency testing - assay variability

Volltext

Referenzen

References
1 Favaloro EJ. Von Willebrand disease: local diagnosis and management of a globally distributed bleeding disorder. Semin Thromb Hemost 2011; 37 (05) 440-455
2 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
3 Colonne CK, Reardon B, Curnow J, Favaloro EJ. Why is misdiagnosis of von Willebrand disease still prevalent and how can we overcome it? A focus on clinical considerations and recommendations. J Blood Med 2021; 12: 755-768
4 Yee A, Kretz CA. Von Willebrand factor: form for function. Semin Thromb Hemost 2014; 40 (01) 17-27
5 Favaloro EJ. Rethinking the diagnosis of von Willebrand disease. Thromb Res 2011; 127 (Suppl. 02) S17-S21
6 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
7 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
8 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
9 Favaloro EJ. Navigating the myriad of von Willebrand factor assays. Hamostaseologie 2020; 40 (04) 431-442
10 Flood VH, Gill JC, Morateck PA. et al. Gain-of-function GPIb ELISA assay for VWF activity in the Zimmerman Program for the Molecular and Clinical Biology of VWD. Blood 2011; 117 (06) e67-e74
11 Patzke J, Favaloro EJ. Laboratory testing for von Willebrand factor activity by glycoprotein Ib binding assays (VWF:GPIb). Methods Mol Biol 2017; 1646: 453-460
12 Favaloro EJ. Evaluation of commercial von Willebrand factor collagen binding assays to assist the discrimination of types 1 and 2 von Willebrand disease. Thromb Haemost 2010; 104 (05) 1009-1021
13 Favaloro EJ, Mohammed S. Evaluation of a von Willebrand factor three test panel and chemiluminescent-based assay system for identification of, and therapy monitoring in, von Willebrand disease. Thromb Res 2016; 141: 202-211
14 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
15 Favaloro EJ, Mohammed S. Laboratory testing for von Willebrand factor collagen binding (VWF:CB). Methods Mol Biol 2017; 1646: 417-433
16 Favaloro EJ, Mohammed S, Vong R. et al. How we diagnose 2M von Willebrand disease (VWD): use of a strategic algorithmic approach to distinguish 2M VWD from other VWD types. Haemophilia 2021; 27 (01) 137-148
17 Favaloro EJ, Pasalic L, Curnow J. Type 2M and Type 2A von Willebrand disease: similar but different. Semin Thromb Hemost 2016; 42 (05) 483-497
18 Favaloro EJ, Franchini M, Lippi G. Biological therapies for von Willebrand disease. Expert Opin Biol Ther 2012; 12 (05) 551-564
19 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
20 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
21 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
22 Hollestelle MJ, Meijers JCM, Meije P. How do laboratories perform von Willebrand disease (VWD) diagnostics and classification of VWD patients? Results from external quality data and an international survey. Semin Thromb Hemost 2022;48(06):in press
23 Jennings I, Reilly-Stitt C, Lowe A, Kitchen S, Walker I. 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. Semin Thromb Hemost 2022;48(06): in press
24 Salazar E, Long TA, Smock KJ. et al. Analysis of College of American Pathologists von Willebrand Factor Proficiency Testing Program. Semin Thromb Hemost 2022;48(06): in press
25 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
26 Ziemba YC, Abdulrehman J, Hollestelle MJ. et al. Diagnostic testing for von Willebrand disease: trends and insights from North American laboratories over the last decade. Semin Thromb Hemost 2022
27 Chen D, Tange JI, Meyers BJ, Pruthi RK, Nichols WL, Heit JA. Validation of an automated latex particle-enhanced immunoturbidimetric von Willebrand factor activity assay. J Thromb Haemost 2011; 9 (10) 1993-2002
28 Mohammed S, Favaloro EJ. Laboratory testing for von Willebrand factor: factor VIII binding (for 2N VWD). Methods Mol Biol 2017; 1646: 461-472
29 Oliver S, Lau KKE, Chapman K, Favaloro EJ. Laboratory testing for Von Willebrand factor multimers. Methods Mol Biol 2017; 1646: 495-511
30 Favaloro EJ, Oliver S, Mohammed S, Vong R. Comparative assessment of von Willebrand factor multimers vs activity for von Willebrand disease using modern contemporary methodologies. Haemophilia 2020; 26 (03) 503-512
31 Flood VH, Gill JC, Morateck PA. et al. Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor. Blood 2010; 116 (02) 280-286
32 Favaloro EJ, Grispo L, Exner T, Koutts J. Development of a simple collagen based ELISA assay aids in the diagnosis of, and permits sensitive discrimination between type I and type II, von Willebrand's disease. Blood Coagul Fibrinolysis 1991; 2 (02) 285-291
33 Favaloro EJ. An update on the von Willebrand factor collagen binding assay: 21 years of age and beyond adolescence but not yet a mature adult. Semin Thromb Hemost 2007; 33 (08) 727-744
34 Favaloro EJ. Utility of the von Willebrand factor collagen binding assay in the diagnosis of von Willebrand disease. Am J Hematol 2017; 92 (01) 114-118
35 Favaloro EJ, Smith J, Petinos P, Hertzberg M, Koutts J. RCPA Quality Assurance Program (QAP) in Haematology Haemostasis Scientific Advisory Panel. Laboratory testing for von Willebrand's disease: an assessment of current diagnostic practice and efficacy by means of a multi-laboratory survey. Thromb Haemost 1999; 82 (04) 1276-1282
36 Favaloro EJ, Thom J, Baker R. Australasian Society for Thrombosis and Haemostasis (ASTH) Emerging Technologies Group. Assessment of current diagnostic practice and efficacy in testing for von Willebrand's disorder: results from the second Australasian multi-laboratory survey. Blood Coagul Fibrinolysis 2000; 11 (08) 729-737
37 Favaloro EJ, Bonar R, Sioufi J. et al; RCPA Quality Assurance Program in Haematology Haemostasis Committee. Laboratory diagnosis of von Willebrand disorder. Current practice in the southern hemisphere. Am J Clin Pathol 2003; 119 (06) 882-893
38 Favaloro EJ, Bonar R, Kershaw G. et al. (on behalf of the RCPA QAP in Haematology). Laboratory diagnosis of von Willebrand Disorder: quality and diagnostic improvements driven by peer review in a multi-laboratory test process. Haemophilia 2004; 10: 232-242
39 Favaloro EJ, Bonar R, Kershaw G. et al; Royal College Of Pathologists Of Australasia Quality Assurance Program In Haematology. Laboratory diagnosis of von Willebrand disorder: use of multiple functional assays reduces diagnostic error rates. Lab Hematol 2005; 11 (02) 91-97
40 Favaloro EJ, 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 (05) 505-513
41 Favaloro EJ, Bonar R, Meiring M, Street A, Marsden K. 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 (02) 346-358
42 Favaloro EJ, Bonar RA, Mohammed S. et al. Type 2M von Willebrand disease - more often misidentified than correctly identified. Haemophilia 2016; 22 (03) e145-e155
43 Favaloro EJ. Rethinking internal quality control and external quality assessment for laboratory diagnostics of von Willebrand disease. Ann Blood 2019; 4: 4
44 Vangenechten I, Mayger K, Smejkal P. et al. A comparative analysis of different automated von Willebrand factor glycoprotein Ib-binding activity assays in well typed von Willebrand disease patients. J Thromb Haemost 2018; 16 (07) 1268-1277
45 Patzke J, Budde U, Huber A. et al. Performance evaluation and multicentre study of a von Willebrand factor activity assay based on GPIb binding in the absence of ristocetin. Blood Coagul Fibrinolysis 2014; 25 (08) 860-870
46 de Maistre E, Volot F, Mourey G. et al. Performance of two new automated assays for measuring von Willebrand activity: HemosIL AcuStar and Innovance. Thromb Haemost 2014; 112 (04) 825-830
47 Graf L, Moffat KA, Carlino SA. et al. Evaluation of an automated method for measuring von Willebrand factor activity in clinical samples without ristocetin. Int J Lab Hematol 2014; 36 (03) 341-351
48 Favaloro EJ, Mohammed S. Towards improved diagnosis of von Willebrand disease: comparative evaluations of several automated von Willebrand factor antigen and activity assays. Thromb Res 2014; 134 (06) 1292-1300
49 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
50 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
51 Favaloro EJ, Pasalic L. Laboratory diagnosis of von Willebrand disease (VWD): geographical perspectives. Semin Thromb Hemost 2022; 48 (06) 750-766