Comparison of the pharmacokinetics of two von Willebrand factor concentrates [Biostate and AHF (High Purity)] in people with von Willebrand disorder

Emmanuel J. Favaloro; John Lloyd; John Rowell; Ross Baker; Kevin Rickard; Geoff Kershaw; Alison Street; Kate Scarff; Giulio Barrese; Darryl Maher; Andrew J. McLachlan

doi:10.1160/TH06-09-0495

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(06): 922-930
DOI: 10.1160/TH06-09-0495

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Comparison of the pharmacokinetics of two von Willebrand factor concentrates [Biostate and AHF (High Purity)] in people with von Willebrand disorder

A randomised cross-over, multi-centre study

Authors

Emmanuel J. Favaloro

¹Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, New South Wales, Australia
John Lloyd

²Haematology, Institute of Medical and Veterinary Science (IMVS), Royal Adelaide Hospital, Adelaide, South Australia, Australia
John Rowell

³Haematology, Royal Brisbane Hospital, Brisbane, Queensland, Australia
Ross Baker

⁴Haematology, Royal Perth Hospital, Perth, Western Australia, Australia
Kevin Rickard

⁵Haematology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
Geoff Kershaw

⁵Haematology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
Alison Street

⁶Haematology, Alfred Hospital, Melbourne, Victoria, Australia
Kate Scarff

⁷CSL Limited, Broadmeadows, Victoria, Australia
Giulio Barrese

⁷CSL Limited, Broadmeadows, Victoria, Australia
Darryl Maher

⁷CSL Limited, Broadmeadows, Victoria, Australia
Andrew J. McLachlan

⁸Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia

Abstract

Summary

Plasma-derived factor concentrates are important in the management of von Willebrand disorder (VWD). In our geographic locality, a single viral inactivation step concentrate (AHF [High Purity]), has been replaced with one using a double viral inactivation step (Biostate^®). The aim of this study was to compare the pharmacokinetics of von Willebrand factor (VWF) and factor VIII (FVIII) after administration of AHF (High Purity) and Biostate^®. This study was a single-blind, randomised cross-over, multi-centre investigation in twelve people with VWD, comprising four type 3, two type 2B, one type 2M and five type 1 VWD. The subjects received a single infusion of 60 IU/kg ristocetin cofactor activity (VWF:RCo) of either AHF (High Purity) or Biostate^®, and after a minimum 15-day wash-out period they received the alternative product. Blood samples were collected for up to 48 hours after each dose for assay of FVIII coagulant activity (FVIII:C) and VWF by VWF:RCo, collagen binding capacity (VWF:CB) and antigen (VWF:Ag). As a measure of delivered VWF ‘functionality’ we calculated the area-under-the-concentration-time-curve (AUC) ratios of VWF:RCo to VWF:Ag and VWF:CB to VWF:Ag. The effect on platelet adhesiveness by PFA-100 closure times (CTs) was measured prior to and 30 minutes post infusion. VWF multimers were also assessed pre and post infusion. Pharmacokinetic parameters after AHF (High Purity) and Biostate^® were in close agreement for VWF:RCo (confirming dosing equivalence). Parameters for other study markers were also similar, although Biostate^® tended to yield relatively lower VWF:Ag and higher VWF:CB levels. Although AHF (High Purity) and Biostate^® resulted in similar levels of high-molecular-weight (HMW) multimers post-infusion, the relative level of HMW to low-molecular-weight (LMW) multimers were determined to be higher following Biostate^®. The relative levels of functional VWF (i.e. VWF:CB and VWF:RCo) to VWF:Ag were also higher in Biostate^® compared to AHF (High Purity). With both study products, PFA-100 CTs 30 minutes post infusion showed minor improvement for only some subjects. In conclusion, the pharmacokinetics of FVIII:C and VWF are not significantly different after administration of AHF (High Purity) and Biostate^®. Study parameters considered as ‘in-vitro’ markers of VWF ‘functionality’ or potential clinical efficacy (i.e. VWF:CB and VWF:RCo relative to VWF:Ag, level of HMW VWF relative to LMW-VWF) were determined to be higher for Biostate^® than AHF (High Purity). PFA-100 CTs did not adequately reflect changes in these VWF parameters. Based on these results, one would expect Biostate^® to be at least as effective, if not superior to AHF (High Purity) for the treatment of VWD.

Keywords

Pharmacokinetics - von Willebrand factor - von Willebrand disease - VWF - von Willebrand disorder - VWD - coagulation factor concentrate

Full Text

References

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