RSS-Feed abonnieren
DOI: 10.1055/s-2002-27818
A Reliable von Willebrand Factor: Ristocetin Cofactor Enzyme-Linked Immunosorbent Assay to Differentiate between Type 1 and Type 2 von Willebrand Disease
Publikationsverlauf
Publikationsdatum:
03. Mai 2002 (online)
![](https://www.thieme-connect.de/media/sth/200202/lookinside/thumbnails/10.1055-s-2002-27818-1.jpg)
ABSTRACT
von Willebrand disease (vWD) is the most common hereditary bleeding disorder due to either a qualitative or a quantitative defect in von Willebrand factor (vWF). vWF is a multimeric plasma protein that plays an important role in (1) primary hemostasis, by sustaining indirect platelet adhesion especially at high shear rates, and in (2) secondary hemostasis, by protecting factor VIIIc (FVIIIc) from degradation. A correct diagnosis of vWD is based on the accurate identification of one of the six different subtypes (type 1, 2A, 2B, 2M, 2N, 3). To do this, different laboratory tests are available. One aspect of the identification is the discrimination between type 1 and type 2 (2A, 2B, and 2M) vWD. In type 1 vWD, both vWF levels (vWF:Ag) and vWF activity (vWF:RCof) are decreased; in type 2, the vWF:Ag level is normal or decreased and vWF:RCof is decreased. Thus, ratios of vWF:Ag to vWF:RiCof above 1 allow identifation of type 2 vWD patients. The currently used vWF:RCof test is an agglutination test in which patients' plasma is added to washed fixed control platelets in the presence of ristocetin and the extent of agglutination is measured. This test suffers from high interlaboratory and intralaboratory variability. We have recently shown that the same vWF:RCof can also be measured in an enzyme-linked immunosorbent assay (ELISA) with a low interassay and intraassay variability and can be used to identify patients suffering from vWD. We here show that our test allows the discrimination between type 1 and type 2 vWD patients.
KEYWORDS
von Willebrand disease - ristocetin cofactor activity - ELISA - diagnosis - factor VIIIc
REFERENCES
- 1 Kehrel B. Platelet-collagen interactions. Semin Thromb Hemost . 1995; 21 123-129
- 2 Sakariassen K S, Bolhuis P A, Sixma J J. Human blood platelet adhesion to artery subendothelium is mediated by factor VIII-Von Willebrand factor bound to the subendothelium. Nature . 1979; 279 636-638
- 3 Savage B, Saldivar E, Ruggeri Z M. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell . 1996; 84 289-297
- 4 Lopez J A, Andrews R K, Afshar-Kharghan V. Bernard-Soulier syndrome. Blood . 1998; 91 4397-4418
- 5 Mazurier C, Ribba A S, Gaucher C. Molecular genetics of von Willebrand disease. Ann Genet . 1998; 41 34-43
- 6 Mohlke K L, Nichols W C, Ginsburg D. The molecular basis of von Willebrand disease. Int J Clin Lab Res . 1999; 29 1-7
- 7 Sadler J E. A revised classification of von Willebrand disease. For the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost . 1994; 71 520-525
- 8 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
- 9 Federici A B. Diagnosis of von Willebrand disease. Haemophilia . 1998; 4 654-660
- 10 Veyradier A, Fressinaud E, Meyer D. Laboratory diagnosis of von Willebrand disease. Int J Clin Lab Res . 1998; 28 201-210
- 11 Favaloro E J, Grispo L, Exner T. 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; 2 285-291
- 12 Favaloro E J, Smith J, Petinos P. Laboratory testing for von Willebrand's disease: an assessment of current diagnostic practice and efficacy by means of a multi-laboratory survey. RCPA Quality Assurance Program (QAP) in Haematology Haemostasis Scientific Advisory Panel. Thromb Haemost . 1999; 82 1276-1282
- 13 Vanhoorelbeke K, Cauwenberghs N, Vauterin S. A reliable and reproducible ELISA method to measure ristocetin cofactor activity of von Willebrand factor. Thromb Haemost . 2000; 83 107-113
- 14 Schumpp-Vonach B, Kresbach G, Schlaeger E J. Stable expression in Chinese hamster ovary cells of a homogeneous recombinant active fragment of human platelet glycoprotein Ib alpha. Cytotechnology . 1995; 17 133-141
- 15 Macfarlane D E, Stibbe J, Kirby E P. A method for assaying von Willebrand factor (ristocetin cofactor). Thrombosis et Diathesis Haemorrhagica (Letter) . 1975; 34 306-308
- 16 Brinkhous K M, Graham J E, Cooper H A. Assay of von Willebrand factor in von Willebrand's disease and hemophilia: use of a macroscopic platelet aggregation test. Thromb Res . 1975; 6 267-272
- 17 Federici A B, Bader R, Pagani S. Binding of von Willebrand factor to glycoproteins Ib and IIb/IIIa complex: affinity is related to multimeric size. Br J Haematol . 1989; 73 93-99
- 18 Fischer B E, Kramer G, Mitterer A. Effect of multimerization of human and recombinant von Willebrand factor on platelet aggregation, binding to collagen and binding of coagulation factor VIII. Thromb Res . 1996; 84 55-66
- 19 de Romeuf C, Hilbert L, Mazurier C. Platelet activation and aggregation induced by recombinant von Willebrand factors reproducing four type 2B von Willebrand disease missense mutations. Thromb Haemost . 1998; 79 211-216
- 20 Vanhoorelbeke K, van der Plas M R, Vandecasteele G. Sequence alignment between vWF and peptides inhibiting the vWF-collagen interaction does not result in the identification of a collagen-binding site in vWF. Thromb Haemost . 2000; 84 621-625
- 21 Brown J E, Bosak J O. An ELISA test for the binding of von Willebrand antigen to collagen. Thromb Res . 1986; 43 303-311
- 22 Favaloro E J, Henniker A, Facey D. Discrimination of von Willebrand's disease (vWD) subtypes: direct comparison of von Willebrand factor:collagen binding assay (vWF:CBA) with monoclonal antibody (MAB) based vWF-capture systems. Thromb Haemost . 2000; 84 541-547
- 23 Favaloro E J. Collagen binding assay for von Willebrand factor (vWF:CBA): detection of von Willebrands disease (vWD), and discrimination of vWD subtypes, depends on collagen source. Thromb Haemost . 2000; 83 127-135
- 24 Murdock P J, Woodhams B J, Matthews K B. 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 1272-1277
- 25 Preston F E. Assays for von Willebrand factor functional activity: a UK NEQAS survey. National External Quality Assessment Scheme. (Letter) (published erratum appears in Thromb Haemost 1999;81:478) . Thromb Haemost . 1998; 80 863
- 26 Hillery C A, Mancuso D J, Evan S J. Type 2M von Willebrand disease: F606I and I662F mutations in the glycoprotein Ib binding domain selectively impair ristocetin- but not botrocetin-mediated binding of von Willebrand factor to platelets. Blood . 1998; 91 1572-1581