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

Emmanuel J. Favaloro; Geoff Kershaw; Andrew J. McLachlan; John Lloyd

doi:10.1055/s-2007-1000367

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2007; 33(8): 745-758
DOI: 10.1055/s-2007-1000367

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

Emmanuel J. Favaloro¹ , Geoff Kershaw² , Andrew J. McLachlan³ , John Lloyd⁴

¹Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, Australia
²Haematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
³Faculty of Pharmacy, University of Sydney, Camperdown, NSW, Australia
⁴Haematology, Institute of Medical and Veterinary Science (IMVS), Royal Adelaide Hospital, Adelaide, SA, Australia

Abstract

ABSTRACT

Plasma-derived factor concentrates are important in the management of von Willebrand disease (VWD). We review the current literature regarding pharmacokinetic studies of von Willebrand factor (VWF) concentrates used to treat VWD. Using additional local experience of a crossover pharmacokinetic (PK) study comparing a currently licensed double virally inactivated concentrate, Biostate, with that of its single virally inactivated predecessor, AHF (High Purity), we propose that consideration now be given to the use of new and novel test parameters for future PK studies. In particular, we propose that an evaluation of VWF collagen binding (VWF:CB) using an assay confirmed to be sensitive to high-molecular-weight forms of VWF be used in all future studies in addition to standard parameters such as factor VIII coagulant (FVIII:C), VWF antigen (VWF:Ag), and ristocetin cofactor (VWF:RCo). We further propose the use of calculated ratios of VWF:RCo to VWF:Ag and VWF:CB capacity to VWF:Ag as a measure of delivered VWF “functionality.” We also report some new data regarding assessment of VWF:multimers using standard procedures together with densitometry and a novel scoring system to support our proposals. We suggest that these test parameters may be useful in future PK studies to better assess and compare the potential utility and clinical efficacy of VWF factor concentrates for use as therapy for VWD.

KEYWORDS

von Willebrand factor - VWF - von Willebrand disease - VWD - coagulation factor concentrate - pharmacokinetics

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Referenzen

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Dr. Emmanuel J FavaloroPh.D. M.A.I.M.S.

Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR)

Westmead Hospital, WSAHS, Westmead, NSW, 2145, Australia

eMail: emmanuel.favaloro@swahs.health.nsw.gov.au