von Willebrand Factor Activity Detected in a Monoclonal Antibody-based ELISA: an Alternative to the Ristocetin Cofactor Platelet Agglutination Assay for Diagnostic Use

Paul J Murdock; Barry J Woodhams; Kathy B Matthews; K John Pasi; Alison H Goodall

doi:10.1055/s-0038-1657727

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1997; 78(04): 1272-1277
DOI: 10.1055/s-0038-1657727

Rapid Communication

Schattauer GmbH Stuttgart

von Willebrand Factor Activity Detected in a Monoclonal Antibody-based ELISA: an Alternative to the Ristocetin Cofactor Platelet Agglutination Assay for Diagnostic Use

Paul J Murdock

The Katharine Dormandy Haemophilia Centre & Haemostasis Unit, Academic Department of Haematology, Royal Free Hampstead NHS Trust Hospital & School of Medicine, London, UK

,

Barry J Woodhams

The Katharine Dormandy Haemophilia Centre & Haemostasis Unit, Academic Department of Haematology, Royal Free Hampstead NHS Trust Hospital & School of Medicine, London, UK

,

Kathy B Matthews

The Katharine Dormandy Haemophilia Centre & Haemostasis Unit, Academic Department of Haematology, Royal Free Hampstead NHS Trust Hospital & School of Medicine, London, UK

,

K John Pasi

The Katharine Dormandy Haemophilia Centre & Haemostasis Unit, Academic Department of Haematology, Royal Free Hampstead NHS Trust Hospital & School of Medicine, London, UK

,

Alison H Goodall

The Katharine Dormandy Haemophilia Centre & Haemostasis Unit, Academic Department of Haematology, Royal Free Hampstead NHS Trust Hospital & School of Medicine, London, UK

› Author Affiliations

Abstract

PDF Download

Summary

The monoclonal antibody RFF-VIII:R/1 recognises an epitope on von Willebrand factor involved in its interaction with GPIbα. A two-site, solid phase ELISA has been established using RFF-VIII:R/1 as the solid-phase, capture antibody and an enzyme-conjugated, polyclonal antibody to human VWF, which provides an assay for VWF functional activity with a detection limit of 0.5 U/dl VWF and an interassay %CV<10. Plasma from 192 VWD patients (48 studied retrospectively; 144 prospectively) showed VWF levels of <50 U/dl in type 1 patients (n = 156), <25 U/dl in type 2A (n = 26) and <35 U/dl in type 2B (n = 8) which, in type 1 and 2A patients, correlated with RiCoF activity (r >0.82). In plasma from patients with type 1 VWD values of VWF in the Mab-based ELISA were similar to levels of VWF:Ag measured in a polyclonal antibody-based ELISA (r >0.87) but were significantly lower than VWF:Ag in type 2A and 2B plasmas (p <0.0005), allowing discrimination of variant VWD. The Mab-based ELISA has advantages of sensitivity and reproducibility over the RiCoF assay to measure VWF activity and can be used to analyse stored samples. In conjunction with an ELISA for VWF:Ag and VWF multimer analysis, it provides a reliable method, for the laboratory diagnosis of VWD.

PDF (1184 kb)

References

References
1 Rodeghiero F, Castaman G, Mannucci PM. Clinical indications for desmopressin (DDAVP) in congenital and acquired von Willebrand disease. Blood Rev 1991; 5: 155-161
2 Giddings JC, Peake IR. The investigation of FVIII deficiency. :In Blood Coagulation and Haemostasis. Thompson JM. ed. New York: Churchill Livingstone: 1985. p. 135-207
3 Zimmerman TS, Hoyer LW, Dickson L, Edgington TS. Determination of the von Willebrand’s disease antigen (Factor VUI-related antigen) in plasma by quantitative immunoelectophoresis. J Lab Clin Med 1975; 86: 152-159
4 Bartlett A, Dormandy KM, Hawkey CM, Stableforth P, Voller A. Factor Vlll-related antigen: measurement by enzyme immunoassay. Br Med J 1976; 1: 994-996
5 Ruggeri ZM, Zimmerman TS. Variant von Willebrand’s disease: characterization of two subtypes by analysis of multimeric composition of factor Vlll/von Willebrand factor in plasma and platelets. J Clin Invest 1980; 65: 1318-1325
6 Howard MA, Firkin BG. Ristocetin – a new tool in the investigation of platelet aggregation. Thrombosis et Diathesis Haemorrhagica 1971; 26: 362-369
7 Allain JP, Cooper HA, Wagner RH, Brinkhous KM. Platelets fixed with paraformaldehyde: a new reagent for assay of von Willebrand factor and platelet aggregation factor. J Lab Clin Med 1975; 85: 318-328
8 Brinkhous KM, Read MS. Preservation of platelet receptors for platelet aggregating factor/von Willebrand factor by air drying, freezing or lyophilization: new stable platelet preparations for von Willebrand factor assays. Thromb Res 1978; 13: 591-597
9 Puri S, Gresham C, Kao KJ. A simple quantitative assay for ristocetin cofactor activity using microtitre plate and ELISA plate reader. Thromb Res 1994; 74: 285-291
10 Bockenstedt P, Greenberg JM, Handin RI. Structural basis of von Willebrand factor binding to platelet glycoprotein lb and collagen. J Clin Invest 1986; 77: 743-749
11 Girma J-P, Chopek MW, Titani K, Davie EW. Limited proteolysis of human von Willebrand factor by Staphylococcus aureus V-8 protease: isolation and partial characterization of a platelet-binding domain. Biochemistry 1986; 25: 3156-3163
12 Fujimura Y, Titani K, Holland LZ, Russell SR, Roberts JR, Elder JH, Ruggeri ZM, Zimmerman TS, von Willebrand factor. A reduced and alkylated 52/48 kDa fragment beginning at amino acid residue 449 contains the domain interacting with platelet glycoprotein lb. J Biol Chem 1986; 261: 381-385
13 Mohri H, Fujimura Y, Shima M, Yoshioka A, Houghten RA, Ruggeri ZM, Zimmerman TS. Structure of the von Willebrand factor domain interacting with glycoprotein lb. J Biol Chem 1988; 263: 17901-17904
14 Bemdt MC, Booth WJ, Andrews RK, Castaldi PA. Definition of von Willebrand factor (vWF)-GPIb-IX complex interaction using vWF-based peptides. Thromb Haemost 1991; 65: 748
15 Sadler JE, von Willebrand disease. In:. Haemostasis and Thrombosis. Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD. eds. Edinburgh: Churchill Livingstone: 1994. p. 843-857
16 Ginsburg D, Sadler JE. von Willebrand disease: A database of point mutations, insertions, and deletions. Thromb Haemost 1993; 69: 177-184
17 Goodall AH, Jarvis J, Chand S, Rawlings E, O’Brien DP, McGraw A, Hutton R, Tuddenham EG. An immunoradiometric assay for human factor Vlll/von Willebrand factor (VIII:vWF) using a monoclonal antibody that defines a functional epitope. Br J Haematol 1985; 59: 565-577
18 Nokes TJ, Mahmoud NA, Savidge GF, Goodall AH, Meyer D, Edgington TS, Hardisty RM. Von Willebrand factor has more than one binding site for platelets. Thromb Res 1984; 34: 361-366
19 Fujimura Y, Miyata S, Nishida S, Miura S, Kaneda M, Yoshioka A, Fukui H, Katayama M, Tuddenham EGD, Usami Y, Titani K. The interaction of botrocetin with normal or variant von Willebrand factor (types IIA and IIB) and its inhibition by monoclonal antibodies that block receptor binding. Thromb Haemost 1992; 68: 464-469
20 Chand S, McCraw A, Hutton R, Tuddenham EG, 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: 318-324
21 Goding JW. Monoclonal antibodies: Principles and Practice. London: Academic Press: 1986. Ed. 2. nd
22 Nesbitt IM, Goodeve AC, Gulliat AM, Makris M, Preston FE, Peake IR. The characterisation of type 2N von Willebrand’s disease using phenotypic and molecular techniques. Thromb Haemost 1996; 75: 959-964
23 Hardisty RM, MacPherson JC. A one stage Factor VIII (antihaemophilic globulin) assay and its use in venous and capillary plasma. Thrombosis et Diathesis Haemorrhagica 1962; 7: 215
24 Brown JE, Bosak JO. An ELISA test for the binding of von Willebrand antigen to collagen. Thromb Res 1986; 43: 303-311
25 Favoloro EJ, Grispo L, Exner T, Koutts J. Development of a simple collagen based ELISA assay aids the diagnosis of , and permits sensitive discrimination between Type I and Type II von Willebrand’s disease. Blood Coag Fibrinolysis 1991; 2: 285-291
26 Favoloro EJ, Grispo L, Dinale A, Bemdt M, Koutts J. von Willebrand’s disease: laboratory investigation using an improved functional assay for von Willebrand factor. Pathology 1993; 25: 152-158
27 Lankhof H, van Hoeji M, Schiphorst E, Bracke M, Wu Y-P, Ijsseldijk MJW, Vink T, de GrootPG, Sixma JJ. A3 domain is essential for interaction of von Willebrand factor with collagen type IE. Thromb Haemost 1996; 75: 950-958
28 Christophe O, Rouault C, Obert B, Pietu G, Meyer D, Girma JP. A monoclonal antibody (B724) to von Willebrand factor recognizing an epitope within the Al disulphide loop (Cys509-Cys695) discriminates between type 2A and type 2B von Willebrand disease. Br J Haematol 1995; 90: 195-203
29 Hamsten A, Blombäck M, Wiman B, Svensson J, Szamosi A, de Fraire U, Mettinger L. Haemostatic function in myocardial infarction. Br Heart J 1986; 55: 58-66
30 Mettinger KL. A study of haemostasis in ischemic cerebrovascular disease I Abnormalities in factor VIII and antithrombin. Thromb Res 1982; 26: 183-192
31 Blann A, Midgley H, Burrows G, Maxwell S, Utting S, Davies M, Waite M, McCollum C. Free radicals, antioxidants and endothelial cell damage after percutaneous transluminal coronary angioplasty. Coronary Art Dis 1993; 4: 905-910
32 Smith FB, Lowe GDO, Fowkes FG, Rumley A, Rumley AG, Donnan PT, Housey E. Smoking, haemostatic factors and lipid peroxides in a population case control study of peripheral arterial disease. Atherosclerosis 1993; 102: 155-162
33 Greaves M, Pickering C, Knight G, Boulton AJM, Ball J, Ward JD, Preston FE. Changes in factor VIII complex in diabetic ketoacidosis: evidence of endothelial cell damage? Diabetologia. 1987; 30: 160-165
34 Pearson JD. Endothelial cell function and thrombosis. Balliere’s Clinical Haematology 1994; 7: 441-452
35 Blann AD, Tabemer DA. A reliable marker of endothelial dysfunction: does is exist? Br J Haematol. 1995; 90: 244-248