An External Quality Assessment Program for von Willebrand Factor Laboratory Analysis: An Overview from the European Concerted Action on Thrombosis and Disabilities Foundation

ABSTRACT

The laboratory diagnosis of von Willebrand disease (vWD) is complex and requires a panel of different laboratory tests. Because of this complexity, a proper quality control process is necessary. Since 2003, the European Concerted Action on Thrombosis and Disabilities Foundation has provided an external quality control program for several laboratory tests included in the diagnosis of vWD. Currently, ~180 different laboratories participate in this program, of which the vast majority perform both von Willebrand factor (vWF):antigen (Ag) and activity tests. The lowest between-laboratory variation was observed for the vWF antigen assay (10 to 24%), with a better performance for the latex immunoassay (8 to 24%) than the enzyme immunoassay (13 to 25%). Both the ristocetin cofactor activity assay (RCo) and the collagen-binding assay showed a higher between-laboratory variation (20 to 40% and 17 to 29%, respectively). We have observed that the within-laboratory repeatability for normal samples ranged from 0 to 40% for the antigen assay and from 0 to 86% for the ristocetin cofactor activity assay. Normal samples were interpreted correctly by the majority of the participants. However, type 1 vWD samples were wrongly interpreted by 20 to 40% of the participants, which was mainly caused by a discordance in the vWF:RCo/vWF:Ag ratio. It can be concluded that further improvement in the laboratory diagnosis of vWD is necessary.

KEYWORDS

von Willebrand disease - von Willebrand factor - von Willebrand factor activity - von Willebrand factor antigen - quality control program

REFERENCES

• 1 Rodeghiero F, Castaman G C, Dini E. Epidemiological investigation of the prevelance of von Willebrand's disease.  Blood. 1987;  69 454-459
• 2 Werner E J, Broxson E H, Tucker E L, Giroux D S, Shults J, Abshire T C. Prevalence of von Willebrand disease in children: a multiethnic study.  J Pediatr. 1993;  123 893-898
• 3 Sadler J E, Mannucci P M, Berntop E et al.. Impact, diagnosis and treatment of von Willebrand disease.  Thromb Haemost. 2000;  84 160-174
• 4 Sadler J E. A revised classification of von Willebrand disease.  Thromb Haemost. 1994;  71 520-525
• 5 Favaloro E J. Appropriate laboratory assessment as a critical facet in the proper diagnosis and subclassification of von Willebrand's disorder.  Best Pract Res Clin Haematol. 2001;  14 299-319
• 6 Budde U, Drewke E, Mainusch K, Schneppenheim R. Laboratory diagnosis of congenital von Willebrand disease.  Semin Thomb Hemost. 2002;  28 173-189
• 7 Schneppenheim R, Budde U. Phenotypic and genotypic diagnosis of von Willebrand disease: a 2004 update.  Semin Hematol. 2005;  42 15-28
• 8 Favaloro E J, Smith J, Petinos P, Hertzberg M, Koutts J. 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 1276-1282
• 9 Favaloro E J, Thom J, Baker R. Assessment of current diagnostic practice and efficacy in testing for von Willebrand's disorder: results form the second Australian multi-laboratory survey.  Blood Coagul Fibrinolysis. 2000;  11 729-737
• 10 Favaloro E J, Bonar R, Sioufi J et al.. Laboratory diagnosis of von Willebrand disorder: current practice in the southern hemisphere.  Am J Clin Pathol. 2003;  119 882-893
• 11 Favaloro E J, Bonar R, Kershaw G et al.. Laboratory diagnosis of von Willebrand's disorder: quality and diagnostic improvements driven by peer review in a multilaboratory test process.  Haemophilia. 2004;  10 232-242
• 12 Favaloro E J, Bonar R, Kershaw G et al.. Laboratory diagnosis of von Willebrand disorder: Use of multiple functional assays reduces diagnostic error rates.  Lab Hematol. 2005;  11 91-97
• 13 Bland J M, Altman D G. Statistical methods for assessing agreement between two methods of clinical measurement.  Lancet. 1986;  i(8476) 307-310
• 14 Casonato A, Pontara E, Bertomoro A, Sartorello F, Cattini M G, Girolami A. Von Willebrand factor collagen binding activity in the diagnosis of von Willebrand disease: an alternative to ristocetin cofactor activity?.  Br J Haematol. 2001;  112 578-583
• 15 Favaloro E J. A duplex issue: (i) time to re-appraise the diagnosis and classification of von Willebrand disorder (VWD), and (ii) clarification of the roles of von Willebrand factor (VWF) collagen binding and ristocetin cofactor activity assays.  Haemophilia. 2002;  8 828-831
• 16 Favaloro E J, Aboud M, Arthur C. Possibility of potential VWD misdiagnosis or misclassification using LIA technology and due to presence of rheumatoid factor.  Am J Hematol. 2001;  66 53-56
• 17 Meijer P, De Maat M PM, Kluft C, Haverkate F, Van Houwelingen H C. Assessment of the long-term analytical performance of field methods in haemostasis by evaluation of results of an external quality assessment programme.  Clin Chem. 2002;  48 1011-1015
• 18 Meijer P, Kluft C, Haverkate F, De Maat M PM. The long-term within- and between-laboratory variability for assay of antithrombin, and proteins C and S: results derived from the external quality assessment program for thrombophilia screening of the ECAT foundation.  J Thromb Haemost. 2003;  1 748-753