Composition, Quality Control, and Labeling of Plasma-Derived Products for the Treatment of von Willebrand disease

ABSTRACT

Different plasma-derived products have been used to treat patients affected with von Willebrand disease (vWD). To ensure optimal product selection, the purification process and viral elimination methods should be considered. Unfortunately, details regarding the degree of purification and viral attenuation achieved for each product typically are limited to the information provided by the package insert. Recently published studies have compared the in vitro characteristics of some of these products. All vary in terms of protein composition, proteins copurified with von Willebrand factor (vWF) and factor (F) VIII, and the characteristics of the active substance. There currently remains a lack of consensus regarding the in vitro characteristics essential to ensure a concentrate optimized for the treatment of vWD. We suggest that the minimal requirements for products on the market for the substitutive treatment of vWD are that they must (1) have the same level of safety in terms of eliminating the potential of blood-borne infections provided by plasma-derived products currently available for hemophilia A patients, (2) contain vWF that promotes adhesion and aggregation of platelets as well as transport and stabilization of FVIII, (3) have been tested for pharmacokinetics and efficacy in patients with different types of vWD before their clinical use for this indication, and (4) be labeled with both vWF and FVIII potency.

KEYWORDS

von Willebrand factor (vWF) - von Willebrand disease (vWD) - ristocetin cofactor activity - factor concentrates - collagen-binding activity

REFERENCES

• 1 Jorpes J E, Blombäck B, Blombäck M et al.. A pilot plant for the preparation of a human plasma fraction containing the human antihaemophilic factor A (factor VIII) and von Willebrand's factor.  Acta Med Scand. 1962;  379(suppl) 7-21
• 2 Perkins H A. Correction of the hemostatic effects in von Willebrand's disease.  Blood. 1967;  30 375-380
• 3 Blatt P M, Brinkhous K M, Culp H R et al.. Antihemophilic factor concentrate therapy in von Willebrand disease: dissociation of bleeding-time factor and ristocetin-cofactor activities.  JAMA. 1976;  236 2770-2772
• 4 Green D, Potter E V. Failure of AHF concentrate to control bleeding in von Willebrand's disease.  Am J Med. 1976;  60 357-360
• 5 Mazurier C, Jorieux S, de Romeuf C et al.. In vitro evaluation of a very-high-purity solvent/detergent treated, von Willebrand factor concentrate.  Vox Sang. 1991;  61 1-7
• 6 Turecek P L, Gritsch H, Pichler L et al.. In vivo characterization of recombinant von Willebrand factor in dogs with von Willebrand disease.  Blood. 1997;  90 3555-3567
• 7 Thompson A R, Gill J C, Ewenstein B M et al.. Successful treatment for patients with von Willebrand disease undergoing urgent surgery using factor VIII/VWF concentrate (Humate P).  Haemophilia. 2004;  10 42-51
• 8 Gill J C, Ewenstein B M, Thompson A R et al.. Successful treatment of urgent bleeding in von Willebrand disease with factor VIII/VWF concentrate (Humate-P^®): use of the ristocetin cofactor assay (VWF:RCo) to measure potency and to guide therapy.  Haemophilia. 2003;  9 688-695
• 9 Mannucci P M, Chediak J, Hanna W et al.. Treatment of von Willebrand disease with a high-purity factor VIII/von Willebrand factor concentrate: a prospective, multicenter study.  Blood. 2002;  99 450-456
• 10 Lillicrap D, Poon M C, Walker I et al.. Efficacy and safety of the factor VIII/von Willebrand factor concentrate, Haemate-P/Humate-P: ristocetin cofactor unit dosing in patients with von Willebrand disease.  Thromb Haemost. 2002;  87 224-230
• 11 Cohen A J, Kessler C M, Ewenstein B M et al.. Management of von Willebrand disease: a survey on current clinical practice from the haemophilia centres of North America.  Haemophilia. 2001;  7 235-241
• 12 Srivastava A, Mathews V, Bhurani D et al.. Successful surgical hemostasis in patients with von Willebrand disease following infusion of Koate^® DVI.  Thromb Haemost. 2002;  87 541-543
• 13 Federici A B. Management of von Willebrand disease with factor VIII/von Willebrand factor concentrates: results from current studies and surveys.  Blood Coagul Fibrinolysis. 2005;  16 S17-S21
• 14 The European Agency for the Evaluation of Medicinal Products .Note for Guidance on Plasma-Derived Medicinal Products. CPMP/269/95, rev. 2. London; Human Medicines Evaluation Unit 1997
• 15 Shord S S, Lindley C M. Coagulation products and their uses.  Am J Health Syst Pharm. 2000;  57 1403-1417
• 16 Lethagen S, Carlson M, Hillarp A. A comparative in vitro evaluation of six von Willebrand factor concentrates.  Haemophilia. 2004;  10 243-249
• 17 Allford S L, Harrison P, Lawrie A S et al.. Von Willebrand factor-cleaving protease activity in congenital thrombotic thrombocytopenic purpura.  Br J Haematol. 2000;  111 1215-1222
• 18 Makris M, Colvin B, Gupta V et al.. Venous thrombosis following the use of intermediate purity FVIII concentrate to treat patients with von Willebrand's disease.  Thromb Haemost. 2002;  88 387-388
• 19 Mannucci P M. Venous thromboembolism in von Willebrand disease.  Thromb Haemost. 2002;  88 378-379
• 20 Mazurier C, Poulle M, Samor B et al.. In vitro study of a triple-secured von Willebrand factor concentrate.  Vox Sang. 2004;  86 100-104
• 21 Favaloro E J, Bukuya M, Martinelli T et al.. A comparative multi-laboratory assessment of three factor VIII/von Willebrand factor concentrates.  Thromb Haemost. 2002;  87 466-476
• 22 Menache D, Aronson D L. New treatments of von Willebrand disease: plasma derived von Willebrand factor concentrates.  Thromb Haemost. 1997;  78 566-570
• 23 Suiter P, Budde U, Metzner H J et al.. Comparison von Willebrand factor activities measured by ristocetin cofactor assay and two different VWF-collagen-binding-assays in VWF/FVIII-concentrates.  J Thromb Haemost. 2003:(suppl; abst);  1667
• 24 Favaloro E J. Collagen binding assay for von Willebrand factor (VWF: CBA): detection of von Willebrand Disease (VWD), and discrimination of VWD subtypes, depends on collagen source.  Thromb Haemost. 2000;  83 127-135
• 25 Neugebauer B M, Goy C, Seitz R. A collagen binding assay: an additional method for von Willebrand factor activity in therapeutic concentrates.  Thromb Haemost. 2002;  88 871-872
• 26 Hubbard A R, Dands D, Chang A C et al.. Standardisation of von Willebrand factor in therapeutic concentrates: calibration of the 1st International standard for von Willebrand factor concentrate (00/514).  Thromb Haemost. 2002;  88 380-386
• 27 Mannucci P M, Moia M, Rebulla P et al.. Correction of the bleeding time in treated patients with severe von Willebrand disease is not solely dependent on the normal multimeric structure of plasma von Willebrand factor.  Am J Hematol. 1987;  25 55-65
• 28 Walter O, Budde U, Muysers C et al.. Determination of high-molecular-weight von Willebrand factor multimers and their impact on specific VWF-activities in VWF/FVIII concentrates.  J Thromb Haemost. 2003(suppl: abst);  1673
• 29 Michiels J J, Gadisseur A, Budde U et al.. Characterization, classification, and treatment of von Willebrand diseases: a critical appraisal of the literature and personal experiences.  Semin Thromb Hemost. 2005;  31 577-601
• 30 Chang P, Aronson D L. Plasma derived von Willebrand factor preparations: collagen binding and ristocetin cofactor activities.  Thromb Haemost. 1997;  78 930-933
• 31 European Directorate for the Quality of Medicines . Project on the von Willebrand factor monograph.  Pharmeuropa. 2005;  17.1 90-92
• 32 Morimoto Y, Yoshioka A, Sugimoto M et al.. Haemostatic management of intraoral bleeding in patients with von Willebrand disease.  Oral Dis. 2005;  11 243-248
• 33 Favaloro E J, Smith J, Petinos P on behalf of the RCPA Quality Assurance Program (QAP) in Hematology Scientific Hemostasis Advisory Panel et al.. 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