In vivo recovery with products of very high purity--assay discrepancies

Haemophilia. 1998 Jul;4(4):641-5. doi: 10.1046/j.1365-2516.1998.440641.x.

Abstract

In view of reports of FVIII assay discrepancies in post-infusion plasma samples depending on methods used, we compared FVIII results run by each of four different methods following infusion of rFVIII (Kogenate). Nine persons with haemophilia A were infused with each of two lots of product. Plasma samples were obtained at baseline, and at 10 min, 30 min, 1, 2, 4, 8, 12, 14, 30 and 48 h post-infusion for measurement of FVIII. FVIII assay methods were chromogenic, and one-stage APTT using three different types of activators: micronized, silica, ellagic acid, and kaolin. The same reference plasma standard was used throughout. Results demonstrated a consistent difference in FVIII values, with chromogenic assays being considerably higher than those run by one-stage assays. The discrepancy was greatest when kaolin was the activator. These results point out the problems in attempting to determine the "correct" FVIII level in patient plasma samples following infusion of high purity FVIII preparations. Potential "pitfalls" include the standard used for defining product potency, the methods, reagents, instrumentation and standards used in assaying plasma samples and, in some instances, the characteristics of the product itself. This situation has considerable cost implications, potential impact on patient care, and makes it difficult to compare results between laboratories.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Biological Assay / standards*
  • Factor VIII / administration & dosage
  • Factor VIII / standards*
  • Hemophilia A / drug therapy*
  • Humans
  • Infusions, Intravenous
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / standards

Substances

  • Recombinant Proteins
  • Factor VIII