An Update on the von Willebrand Factor Collagen Binding Assay: 21 Years of Age and Beyond Adolescence but Not Yet a Mature Adult

ABSTRACT

von Willebrand disease (VWD) is considered to be the most common inherited bleeding disorder. It is diagnosed after a clinical and physical review, with personal and familial evidence of (primarily mucocutaneous) bleeding, and confirmed by laboratory testing. The latter typically entails initial plasma testing of factor VIII coagulant (FVIII:C), von Willebrand factor (VWF) protein (antigen; VWF:Ag), and VWF function, which has classically been assessed using the ristocetin cofactor (VWF:RCo) assay. More recent attention has focused on another functional VWF assay, the collagen binding (VWF:CB) assay, as a possible replacement for the VWF:RCo assay or as a supplementary test of VWF adhesive “activity.” Additional laboratory testing can comprise a battery of confirmatory and VWD subtype assisting assays, including assessment of VWF:multimers. This review updates our knowledge of VWD diagnostics with a particular emphasis on the VWF:CB assay. There is good evidence now in place that an optimized VWF:CB assay can significantly reduce the diagnostic error rate otherwise arising from the use of a test panel restricted to including the VWF:RCo assay as the sole functional VWF assay. Nevertheless, the VWF:CB assay should not be used to wholly replace the VWF:RCo assay in phenotypic testing but rather as a supplementary assay. However, with some thought and justification, the VWF:CB assay can be used to partly replace the VWF:RCo assay in some “screening” applications and can also be used to abrogate the need to perform routine VWF:multimers in most test cases.

von Willebrand Factor - VWF - von Willebrand disorder - von Willebrand disease - VWD - collagen binding - VWF:CB - ristocetin cofactor - VWF:RCo - multimers

REFERENCES

• 1 Brown J E, Bosak J O. An ELISA test for the binding of von Willebrand antigen to collagen.  Thromb Res. 1986;  43 303-311
• 2 Favaloro E J. Collagen binding assay for von Willebrand factor (VWF:CBA): detection of von Willebrand's disease (VWD), and discrimination of VWD subtypes, depends on collagen source.  Thromb Haemost. 2000;  83 127-135
• 3 Favaloro E J. Discrimination of von Willebrand's disease (VWD) subtypes: direct comparison of commercial ELISA-based options used to detect qualitative von Willebrand factor (VWF) defects.  Am J Clin Pathol. 2000;  114 608-618
• 4 Favaloro E J. von Willebrand factor (VWF) collagen binding (activity) assay (VWF:CBA) in the diagnosis of von Willebrand's disorder (VWD): a 15-year journey.  Semin Thromb Hemost. 2002;  28 191-202
• 5 Federici A B, Canciani M T, Forza I, Cozzi G. Ristocetin cofactor and collagen binding activities normalized to antigen levels for a rapid diagnosis of type 2 von Willebrand disease. Single center comparison of four different assays.  Thromb Haemost. 2000;  84 1127-1128
• 6 Veyradier A, Trossaert M, Lefrancois A, Fressinaud E, von Meyer D. Willebrand factor collagen binding assay with a commercial kit using type III collagen in von Willebrand disease type 2.  J Thromb Haemost. 2007;  5 868-870
• 7 Sadler J E, Mannucci P M, Berntorp E et al.. Impact, diagnosis and treatment of von Willebrand disease.  Thromb Haemost. 2000;  84 160-174
• 8 Sadler J E, Budde U, Eikenboom J CJ et al.. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand factor.  J Thromb Haemost. 2006;  4 2103-2114
• 9 Favaloro E J. Laboratory identification of von Willebrand disease: technical and scientific perspectives.  Semin Thromb Hemost. 2006;  32 456-471
• 10 Favaloro E J, Bonar R, Meiring M, Street A, Marsden K. (on behalf of the 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;  98 346-358
• 11 Favaloro E J. A duplex issue: (i) time to re-appraise the diagnosis and classification of von Willebrand disorder, and (ii) clarification of the roles of von Willebrand factor collagen binding and ristocetin cofactor activity assays.  Haemophilia. 2002;  8 828-831
• 12 Keeling D. Time for a redefinition of type 2M von Willebrand disease.  Br J Haematol. 2002;  118 922
• 13 Howard M A, Firkin B G. Ristocetin: a new tool in the investigation of platelet aggregation.  Thromb Diath Haemorrh. 1971;  26 362-369
• 14 Howard M A, Sawers R J, Firkin B G. Ristocetin: a means of differentiating von Willebrand's disease into two groups.  Blood. 1973;  41 687-690
• 15 Weiss H J, Hoyer L W, Rickles F R et al.. Quantitative assay of a plasma factor, deficient in von Willebrand's disease, that is necessary for platelet aggregation. Relationship to factor VIII pro-coagulant activity and antigen content.  J Clin Invest. 1973;  52 2708-2716
• 16 Favaloro E J, Bonar R, Kershaw G et al. (on behalf of the RCPA QAP in Haematology). 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;  32 505-513
• 17 Castaman G, Federici A B, Rodeghiero F, Mannucci P M. Von Willebrand's disease in the year 2003: towards the complete identification of gene defects for correct diagnosis and treatment.  Haematologica. 2003;  88 94-108
• 18 Goodeve A, Eikenboom J, Castaman G et al.. Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD).  Blood. 2007;  109 112-121
• 19 James P D, Paterson A D, Notley C and Association of Hemophilia Clinic Directors of Canada et al. Genetic linkage and association analysis in type 1 von Willebrand disease: results from the Canadian type 1 VWD study.  J Thromb Haemost. 2006;  4 783-792
• 20 James P D, Notley C, Hegadorn C et al.. The mutational spectrum of type 1 von Willebrand disease: results from a Canadian cohort study.  Blood. 2007;  109 145-154
• 21 Cumming A, Grundy P, Keeney S et al.. An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease.  Thromb Haemost. 2006;  96 630-641
• 22 Laffan M, Brown S A, Collins P W et al.. The diagnosis of von Willebrand disease: a guideline from the UK Haemophilia Centre Doctors' Organization.  Haemophilia. 2004;  10 199-217
• 23 Favaloro E J, Smith J, Petinos P, Hertzberg M, Koutts J. on behalf of the RCPA Quality Assurance Program (QAP) in Hematology Scientific Hemostasis 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 1276-1282
• 24 Favaloro E J, Thom J, Baker R. on behalf of the 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;  11 729-738
• 25 Ribba A-S, Loisel I, Lavergne J-M et al.. Ser968Thr mutation within the A3 domain of Von Willebrand factor (VWF) in two related patients leads to a defective binding of VWF to collagen.  Thromb Haemost. 2001;  86 848-854
• 26 Favaloro E J, Soltani S, McDonald J. Potential laboratory misdiagnosis of haemophilia and von Willebrand disorder due to cold activation of blood samples for testing.  Am J Clin Pathol. 2004;  122 686-692
• 27 Favaloro E J. Pre-analytical variables in coagulation testing.  Blood Coagul Fibrinolysis. 2007;  18 86-89
• 28 Moroi M, Jung S M. A mechanism to safeguard platelet adhesion under high shear flow: von Willebrand factor-glycoprotein Ib and integrin alphabeta-collagen interactions make complementary, collagen-type-specific contributions to adhesion.  J Thromb Haemost. 2007;  5 797-803
• 29 Lisman T, Raynal N, Groeneveld D et al.. A single high-affinity binding site for von Willebrand factor in collagen III, identified using synthetic triple-helical peptides.  Blood. 2006;  108 3753-3756
• 30 Favaloro E J, Koutts J. Laboratory assays for von Willebrand Factor: relative contribution to the diagnosis of von Willebrand's disease.  Pathology. 1997;  29 385-391
• 31 Adcock D M, Bethel M, Valcour A. Diagnosing von Willebrand disease: a large reference laboratory's perspective.  Semin Thromb Hemost. 2006;  32 472-479
• 32 Favaloro E J, Lloyd J, Rowell J et al.. A cross-over, multi-centre study to compare pharmacokinetics of two factor concentrates (Biostate^® and AHF (High Purity)) in people with von Willebrand disorder.  Thromb Haemost. 2007;  97 922-930
• 33 Favaloro E J, Kershaw G, McLachlan A J, Lloyd J. Time to think outside the box? Proposals for a new approach to future pharmacokinetic studies of von Willebrand factor concentrates in people with von Willebrand disease.  Semin Thromb Hemost. 2007;  33 745-758
• 34 Favaloro E J, Bukuya M, Martinelli T et al.. A comparative multi-laboratory assessment of factor concentrate and implications for clinical efficacy as potential replacement therapy in von Willebrand's disease (VWD).  Thromb Haemost. 2002;  87 466-476
• 35 Favaloro E J, Dean M, Grispo L, Exner T, von Koutts J. Willebrand's disease: use of collagen binding assay provides potential improvement to laboratory monitoring of desmopressin (DDAVP) therapy.  Am J Hematol. 1994;  45 205-211
• 36 Favaloro E J, Kershaw G, Bukuya M, Hertzberg M, Koutts J. Laboratory diagnosis of von Willebrand disorder (VWD) and monitoring of DDAVP therapy: efficacy of the PFA-100^® and VWF:CBA as combined diagnostic strategies.  Haemophilia. 2001;  7 180-189
• 37 Favaloro E J. Laboratory monitoring of therapy in von Willebrand disease: efficacy of the PFA-100^® and VWF:CB as coupled strategies.  Semin Thromb Hemost. 2006;  32 566-576
• 38 Favaloro E J. Standardization, regulation, quality assurance and emerging technologies in hemostasis: issues, controversies, benefits and limitations.  Semin Thromb Hemost. 2007;  33 290-297
• 39 Baronciani L, Federici A B, Cozzi G, Canciani M T, Mannucci P M. von Willebrand factor collagen binding assay in von Willebrand disease type 2A, 2B, and 2M.  J Thromb Haemost. 2006;  4 2088-2090
• 40 Hubbard A R. von Willebrand factor standards for plasma and concentrate testing.  Semin Thromb Hemost. 2006;  32 522-528
• 41 Neugebauer B M, Goy C, Budek I, Seitz R. Comparison of two von Willebrand factor collagen binding assays with different affinities for low, medium and high multimers of von Willebrand factor.  Semin Thromb Hemost. 2002;  28 139-147