Laboratory Testing for von Willebrand’s Disease: An Assessment of Current Diagnostic Practice and Efficacy by Means of a Multi-laboratory Survey

Emmanuel J. Favaloro; Julian Smith; Penny Petinos; Mark Hertzberg; Jerry Koutts; the RCPA Quality Assurance Program (QAP) in Haematology Haemostasis Scientific Advisory Panel; on behalf of

doi:10.1055/s-0037-1614375

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(04): 1276-1282
DOI: 10.1055/s-0037-1614375

Review Article

Schattauer GmbH

Laboratory Testing for von Willebrand’s Disease: An Assessment of Current Diagnostic Practice and Efficacy by Means of a Multi-laboratory Survey

Emmanuel J. Favaloro

¹From the Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Western Sydney Area Health Service, Westmead, NSW, Australia

,

Julian Smith

¹From the Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Western Sydney Area Health Service, Westmead, NSW, Australia

,

Penny Petinos

¹From the Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Western Sydney Area Health Service, Westmead, NSW, Australia

,

Mark Hertzberg

¹From the Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Western Sydney Area Health Service, Westmead, NSW, Australia

,

Jerry Koutts

¹From the Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Western Sydney Area Health Service, Westmead, NSW, Australia

› Author Affiliations

the RCPA Quality Assurance Program (QAP) in Haematology Haemostasis Scientific Advisory Panel

Abstract

Summary

We report an evaluation of current laboratory practice for the diagnosis of von Willebrand’s disease (VWD) by means of a multilaboratory survey. This assessment was undertaken with the RCPA Quality Assurance Program (QAP) in Haematology, which covers a wide geographic area encompassing Australia, New Zealand and Asia. A total of 25 laboratories actively involved in testing for VWD were selected to participate in a sample testing assessment exercise. Samples comprised 10 plasmas: (i) a normal plasma pool (in duplicate), (ii) this pool diluted to 50% (in duplicate), (iii) a normal individual (×1), (iv) severe Type 1 VWD (×1), (v) Type 2B VWD (×2 unrelated donors), (vi) Type 3 VWD (×1), (vii) Type 2A VWD (×1). Laboratories were asked to perform all tests available to them in order to establish a laboratory diagnosis of VWD, and then to comment on the possibility or otherwise of VWD. Overall findings indicated a wide variation in test practice, in the effectiveness of various test procedures in detecting VWD, and in the ability of various composite test panels to identify type 2 VWD subtypes. Firstly, while all laboratories (n = 25) performed tests for FVIII:C activity, von Willebrand factor ‘antigen’ (VWF:Ag) and a functional VWF assay [using the ristocetin cofactor assay (VWF:RCo; n = 23) and/or the collagen binding assay (VWF:CBA; n = 12)], only three laboratories carried out VWF:Multimer analysis. Secondly, for the three quantitative VWF assays, 10/25 (40%) laboratories performed all three, whereas 15/25 (60%) performed only two [VWF:Ag and VWF:RCo (n = 13); VWF:Ag and VWF:CBA (n = 2)]. Thirdly, a variety of assay methodologies were evident for VWF:Ag [ELISA, electro-immuno diffusion (EID), latex immuno-assay (LIA), and VIDAS assay] and VWF:RCo (platelet agglutination/‘aggregometry’ and a ‘functional VWF:RCo-alternative’ ELISA assay). Between method analysis for the quantitative VWF assays showed that the VWF:RCo yielded the greatest degree of inter-laboratory assay variation, and had the poorest overall performance with respect to sensitivity to low levels of VWF. The VWF:CBA also performed better than the VWF:RCo in terms of ability to detect functional VWF ‘discordance’ (i.e. Type 2 VWD). Within VWF:Ag method analysis showed that the EID assay procedure was associated with the greatest variation in assay

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References

References
1 Sadler JE, Gralnick HR. Commentary: A new classification for von Willebrand Disease. Blood 1994; 84: 676-9.
2 Sadler JE. Review: Von Willebrand Factor. J Biol Chem 1991; 266: 22777-80.
3 Moroose R, Hoyer LW. von Willebrand factor and platelet function. Ann Rev Med 1986; 37: 157-63.
4 Giddings JC, Peake IR. The investigation of factor VIII deficiency. In: Thompson JM. ed. Blood Coagulation and Haemostasis. New York: Churchill Livingstone; 1985: 135-207.
5 Girma J-P, Meyer D, Verweij CL. et al. Structure-function relationship of human von Willebrand factor. Blood 1987; 70: 605-11.
6 Sadler JE. A revised classification of von Willebrand Disease. For the Subcommittee on von Willebrand Factor of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 1994; 71: 520-5.
7 Guidelines for the diagnosis and management of von Willebrand Disease. Prepared by the Von Willebrand Working Party of the United Kingdom Haemophilia Centre Directors’ Organisation. 1995
8 Sadler JE, Foster PA, George JN. Haemostasis/Platelets. In: Haematology 1996. The Education Program of the American Society of Hematology. McArthur JR. (ed) 79-94.
9 Favaloro EJ, Koutts J. Laboratory assays for von Willebrand Factor: Relative contribution to the diagnosis of von Willebrand’s disease. Pathology 1997; 29: 385-391.
10 Brown RA, Rodgers GM. von Willebrand’s Disease. Check Sample. Clinical Haematology No. CH 96-4 (CH-14). American Society of Clinical Pathologists 1996. 45-62.
11 Fleming TGM. von Willebrand factor: its function and its measurement in the laboratory. Br J Biomed Sci 1995; 52: 50-7.
12 Favaloro EJ, Grispo L, Dinale A, Berndt M, Koutts J. von Willebrand’s Disease: Laboratory investigation using an improved functional assay for von Willebrand factor. Pathology 1993; 25: 152-8.
13 Favaloro EJ, Facey D, Grispo L. Laboratory assessment of von Willebrand factor: Use of different assays can influence the diagnosis of von Willebrand’s disease, dependent on differing sensitivity to sample preparation and differential recognition of high molecular weight VWF forms. Am J Clin Pathol 1995; 104: 264-71.
14 Goodall AH, Jarvis J, Chand S, Rawlings E, O’Brien DP, McCraw A, Hutton R, Tuddenham EGD. An immunoradiometric assay for human factor VIII von Willebrand factor (VIII:VWF) using a monoclonal antibody based that defines a functional epitope. Br J Haem 1985; 59: 565-77.
15 Chand S, McCraw A, Hutton R, Tuddenham EGD, Goodall AH. A two-site, monoclonal antibody based immunoassay for von Willebrand factor – Demonstration that VWF function resides in a conformational epitope. Thromb Haemost 1986; 55: 318-24.
16 Murdock PJ, Woodhams BJ, Mathews KB, Pasi KJ, Goodall AH. von Willebrand factor activity detected in a monoclonal antibody-based ELISA: an alternative to the Ristocetin cofactor platelet agglutination assay for diagnostic use. Thromb Haemost 1997; 78: 1272-7.
17 Fischer BE, Thomas KB, Dorner F. von Willebrand factor: measuring its antigen of function? Correlation between the level of antigen, activity, and multimer size using various detection systems. Thromb Res 1998; 91: 39-43.
18 Casonato A, Pontara E, Bertomoro A, Zucchetto S, Zerbinati P, Girlami A. Abnormal collagen binding activity of 2A von Willebrand factor: evidence that the defect depends only on the lack of large multimers. J Lab Clin Med 1997; 129: 251-9.
19 Preston FE. Assays for von Willebrand Factor Functional Activity: A UK NEQAS Survey. Thromb Haemost 1998; 80: 863.