Presurgical pharmacokinetic analysis of a von Willebrand factor/factor VIII (VWF/FVIII) concentrate in patients with von Willebrand's disease (VWD) has limited value in dosing for surgery

J. Di Paola, S. Lethagen, J. Gill, P. Mannucci, M. Manco-Johnson, J. Bernstein, W. L. Nichols, G. E. Bergman

Research output: Contribution to journalArticle

Abstract

Optimal doses of von Willebrand Factor/Factor VIII (VWF/FVIII) concentrates for surgical procedures in patients with VWD need to be determined. A prospective, multicenter study was performed that included an initial pharmacokinetic (PK) assessment following a standard dose of VWF/FVIII concentrate (Humate-P ®) to determine individual PK parameters and guide therapeutic dosing during surgery. Forty one subjects received 60IU kg -1 VWF: RCo. Median plasma levels, half-life, mean change from baseline and in vivo recovery (IVR) values were determined for VWF:RCo, VWF:Ag, and FVIII: C, and area under the plasma time-concentration curve (AUC), mean residence time (MRT), clearance, volume of distribution and dose linearity were also assessed for VWF:RCo at various time points. Median baseline VWF:RCo level was 13IU dL -1 (range, 6-124); with a mean change from baseline >100IU dL -1 immediately after the infusion, decreasing to 10IU dL -1 at 48h postinfusion. The group median incremental in vivo recovery (IVR) for VWF:RCo was 2.4IU dL -1 per IU kg -1, for VWF:Ag 2.3IU dL -1kg -1 and for FVIII:C was 2.7IU dL -1 per IU kg -1. When analysing individual recovery values on repeated infusions, a very weak correlation was observed between presurgery IVR and IVR for both VWF:RCo and FVIII, measured at various times just prior to and after the surgical procedure. Although group median values were fairly consistent among repeated IVR measurements, the intra-individual IVR values for FVIII and VWF:RCo with repeated infusions showed a large degree of variability. IVR values obtained from pharmacokinetic analyses performed in advance of anticipated surgery do not reliably predict postinfusion circulating levels of VWF:RCo or FVIII attained preoperatively or with subsequent peri-operative infusions.

Original languageEnglish
Pages (from-to)752-758
Number of pages7
JournalHaemophilia
Volume17
Issue number5
DOIs
Publication statusPublished - Sep 2011

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Keywords

  • Pharamacokinetics
  • VWD
  • VWF concentrates

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

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