In vitro studies, pharmacokinetic studies and clinical use of a high purity double virus inactivated FVIII/VWF concentrate (Immunate) in the treatment of von Willebrand disease

Kristien M. M. Ver Elst; Huub D. M. van Vliet; Mies C. Kappers-Klunne; Frank W. G. Leebeek

doi:10.1160/TH04-02-0107

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(01): 67-74
DOI: 10.1160/TH04-02-0107

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

In vitro studies, pharmacokinetic studies and clinical use of a high purity double virus inactivated FVIII/VWF concentrate (Immunate) in the treatment of von Willebrand disease

Kristien M. M. Ver Elst

¹Department of Haematology, Erasmus Medical Center, Rotterdam,The Netherlands

,

Huub D. M. van Vliet

¹Department of Haematology, Erasmus Medical Center, Rotterdam,The Netherlands

,

Mies C. Kappers-Klunne

¹Department of Haematology, Erasmus Medical Center, Rotterdam,The Netherlands

,

Frank W. G. Leebeek

¹Department of Haematology, Erasmus Medical Center, Rotterdam,The Netherlands

› Author Affiliations

Abstract

Summary

Patients with type 2 and 3 von Willebrand disease (VWD) are treated with factor VIII/VWF concentrate in case of bleeding or surgery. Immunate® (Baxter, Vienna, Austria) is a double virus inactivated FVIII/VWF concentrate and is registered in several countries for patients with VWD with reduced FVIII levels.We performed an in vitro, a pharmacokinetic and a clinical study to evaluate Immunate in VWD. In vitro studies showed a significant variation in VWF levels in 9 different batches. The median (range) values (in IU/mL) were 1.10 (0.98-1.30) for FVIII:C, 1.34 (0.95-1.61) for VWF:Ag, 0.60 (0.27-1.08) for VWF:CBA and 0.73 (0.59-0.94) for VWF:RCo. The relatively low VWF activity is mainly due to the lack of high molecular weight multimers (HMWM), as determined by electrophoresis. A pharmacokinetic study showed, based on a content of FVIII:C of 1 U/mL, in vivo recoveries (%) of 106 (56-150) (median and range) for FVIII:C, 105 (62-187) for VWF:Ag, 25 (7-41) for VWF:CBA and 43 (11-76) for VWF:RCo. Half-lives were 14.1 h (7.4-36.9) for FVIII:C, 10.8 h (7.7-26.2) for VWF:Ag, 15.3 h (7.8-44.6) for VWF:CBA and 16.4 h (4.2-26.5) for VWF:RCo. In a clinical study efficacy was determined after infusion given before surgery or dental extractions in ten patients. In two patients the hemostatic response was classified as inadequate. In conclusion, there is a wide variability in VWF concentration and activity in various batches of Immunate®. In the clinical study in which the dosage was based on FVIII:C contents of the concentrate, two out of ten patients had an insufficient haemostatic response. Therefore dosing of Immunate dosing should not be based on FVIII:C levels, but should be based on VWF activity of the individual batches. Future studies using a VWF activity-guided dosage regimen have to be performed to establish the efficacy of Immunate in the treatment of von Willebrand disease.

Keywords

von Willebrand disease - factor VIII/VWF concentrate - bleeding - pharmacokinetics

Full Text

References

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