Study of a Proposed International Standard for Blood Coagulation Factor IX^[*]

Summary

An International Collaborative Study was organized to establish a standard for factor IX. Two freeze-dried concentrate preparations, C₁ and C₂, and one freeze-dried plasma P were compared with each other, with fresh normal plasmas and with local standards in 13 laboratories. One of the concentrate preparations (C₁) contained heparin and this gave rise to non-parallel assays in laboratories testing concentrate C₁ in dilutions containing more than 0.05 i.u. of heparin per ml.

Assays of factor IX showed good precision for both plasma and concentrate in all laboratories; no systematic effect of method, operator or day of assay was detected.

The plasma preparation P and the concentrate preparation C₂ were compared with 59 individual fresh normal plasma samples, and a mean potency ratio of 0.78 (95% confidence Hmits 0.73-0.84) for plasma and 5.62 (95 % confidence limits 5.13-6.16) for the concentrate C₂ obtained. Only 21 estimates of concentrate C₁ in terms of fresh plasma were obtained giving a mean potency ratio of 3.85 (95% confidence limits 1.87—7.92).

The estimated loss of potency for freeze-dried plasma stored at — 20° C is approximately 0.4% per year. The concentrate C₂ is apparently more stable and only very small losses occurred even at higher storage temperatures.

All participants agreed that the preparation C₂ would be suitable to serve as an International Standard for factor IX; they also agreed that the figure assigned for the unitage should be based on the number of ml of ‘average fresh normal plasma’ estimated to contain the factor IX activity of one ampoule of the preparation. It is proposed to recommend to the World Health Organization that the preparation of factor IX concentrate C₂, in ampoules coded 72/32, be considered for establishment as the International Standard for factor IX, and that the international unit for factor IX be assigned on the basis of 5.62 units per ampoule of this preparation.

^* In collaboration with the Sub-Committee on Standards of the International Committee on Thrombosis and Haemostasis.

^** Present address: Northwick Park Hospital and Clinical Research Centre Harrow, Middlesex.

^*** Present address: Department of Statistics, University of Glasgow.

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