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DOI: 10.1055/s-2006-949668
Comparative Analysis and Classification of von Willebrand Factor/Factor VIII Concentrates: Impact on Treatment of Patients with von Willebrand Disease
Publikationsverlauf
Publikationsdatum:
15. September 2006 (online)
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ABSTRACT
von Willebrand disease (vWD) is a bleeding disorder that results from defects in the quality or quantity of von Willebrand factor (vWF), a glycoprotein essential for normal thrombus formation. vWF circulates in plasma as multimers in sizes ranging up to 20,000 kd. The high molecular weight vWF (HMWvWF) multimers are most essential for primary hemostasis, whereas the lower molecular weight multimers are less functionally active. For many patients, the treatment of choice is factor replacement with a vWF/FVIII concentrate, preferably one with a high content of HMWvWF multimers. Given that the commercially available vWF/FVIII concentrates seem to differ substantially in their biochemical properties as well as in their clinical efficacy, we did a comparative study with 12 vWF/FVIII concentrates to investigate content and activities of FVIII and vWF, as well as the content of HMWvWF multimers. The content of HMWvWF multimers varied considerably among the 12 concentrates. The specific vWF activities, as assessed by ristocetin cofactor activity (vWF:RCo) and collagen-binding activity (vWF:CB), correlated well with the HMWvWF content of the products. Of the products tested, Haemate P/Humate-P had the highest content of HMWvWF multimers (with a multimer pattern closest to that of normal human plasma), the highest specific vWF activities, and the highest values of vWF:RCo and vWF:CB per unit of FVIII:coagulant (C). The goal of bleeding prophylaxis and treatment in type 2, severe type 1, and type 3 vWD patients is to normalize vWF activities (vWF:RCo and vWF:CB) and FVIII:C preferentially by vWF/FVIII concentrates containing the high vWF multimers and a high vWF:RCo/FVIII ratio to achieve normal primary and secondary hemostasis. Based on the present study of a comparative analysis of currently available vWF/FVIII concentrates, a classification of vWF/FVIII products is proposed.
KEYWORDS
Hemostasis - von Willebrand disease (vWD) - von Willebrand factor (vWF) - factor VIII - vWF multimers - ristocetin cofactor activity - collagen-binding activity - classification of vWF products
REFERENCES
- 1 Keeney S, Cumming A M. The molecular biology of von Willebrand disease. Clin Lab Haematol. 2001; 23 209-230
- 2 Favaloro E J. Laboratory assessment as a critical component of the appropriate diagnosis and sub-classification of von Willebrand's disease. Blood Rev. 1999; 13 185-204
- 3 Furlan M. Von Willebrand factor: molecular size and functional activity. Ann Hematol. 1996; 72 341-348
- 4 Lethagen S, Carlson M, Hillarp A. A comparative in vitro evaluation of six von Willebrand factor concentrates. Haemophilia. 2004; 10 243-249
- 5 Sadler J E, Mannucci P M, Berntorp E et al.. Impact, diagnosis and treatment of von Willebrand disease. Thromb Haemost. 2000; 84 160-174
- 6 Budde U, Drewke E, Mainusch K, Schneppenheim R. Laboratory diagnosis of congenital von Willebrand disease. Semin Thromb Hemost. 2002; 28 173-189
- 7 Mannucci P M, Bloom A L, Larrieu M J, Nilssen J M. Atherosclerosis and von Willebrand factor: I. Prevalence of von Willebrand's disease in Western Europe and Israel. Br J Haematol. 1984; 57 163-169
- 8 Sadler J E, Mannucci P M, Berntorp E et al.. Impact, diagnosis and treatment of von Willebrand disease. Thromb Haemost. 2000; 84 160-174
- 9 Castaman G. Epidemiology and diagnosis of von Willebrand's disease. Haematologica. 2001; 86(suppl 2) 1-9
- 10 Federici A B, Mannucci P M. Optimizing therapy with factor VIII/von Willebrand factor concentrates in von Willebrand disease. Haemophilia. 1998; 4(suppl 3) 7-10
- 11 Ruggeri Z M. Structure of von Willebrand factor and its function in platelet adhesion and thrombus formation. Baillieres Best Pract Res Clin Haematol. 2001; 14(2) 257-279
- 12 Tsai H-M. Shear stress and von Willebrand factor in health and disease. Semin Thromb Hemost. 2003; 29 479-488
- 13 Sugimoto M, Matsui H, Mizuno T et al.. Mural thrombus generation in type 2A and 2B von Willebrand disease under flow conditions. Blood. 2003; 101 915-920
- 14 Favaloro E J, Bukuya M, Martinneli T et al.. A comparative multi-laboratory assessment of three factor VIII/von Willebrand factor concentrates. Thromb Haemost. 2002; 87 466-476
- 15 Metzner H J, Hermentin P, Cuesta-Linker T et al.. Characterization of factor VIII/von Willebrand factor concentrates using a modified method of von Willebrand factor multimer analysis. Haemophilia. 1998; 4(suppl 3) 25-32
- 16 Neugebauer B M, Goy C, Budek I, Seitz R. Comparison of two von Willebrand factor collagen-binding assays with different binding affinities for low, medium, and high multimers of von Willebrand factor. Semin Thromb Hemost. 2002; 28 139-147
- 17 Favaloro E J. Appropriate laboratory assessment as a critical facet in the proper diagnosis and classification of von Willebrand's disorder. Baillieres Best Pract Res Clin Haematol. 2001; 14(2) 299-319
- 18 Federici A B, Castaman G, Mannucci P M. Guidelines for the diagnosis and management of von Willebrand disease in Italy. Haemophilia. 2002; 8 607-621
- 19 Budde U, Schneppenheim R, Plendi H et al.. Luminographic detection of von Willebrand factor multimers in agarose gels on nitrocellulose membranes. Thromb Haemost. 1990; 63 312-315
- 20 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
- 21 Scharrer I. Diagnosis and management of coagulation disorders in orthopedic surgery. Orthopade. 1999; 28 316-322
- 22 Berntorp E. Von Willebrand factor containing factor VIII concentrates. Haemophilia. 1999; 5(suppl 2) 60-63
- 23 Goudemand J, Scharrer I, Berntorp E et al.. Pharmacokinetic studies on Wilfactin®, a von Willebrand factor concentrate with a low factor VIII content treated with three virus-inactivation/removal methods. J Thromb Haemost. 2005; 3 1-9
- 24 Barrowcliffe T W. Recommendation for the assay of high-purity factor VIII concentrtates. Thromb Haemost. 1993; 70 876-877
Ulrich BuddeM.D.
Coagulation Laboratory, Laboratory Association Prof. Arndt and Partners
Lademannbogen 61-63, D 22339 Hamburg, Germany
eMail: budde@labor-arndt-partner.de