Assaying Factor Concentrates

Assaying Factor Concentrates
Jan 30, 2019 7:53am

A pre-publication article, Young G, Perry D, The International Prophylaxis Study Group (IPSG). Laboratory assay measurement of modified clotting factor concentrates: a review of the literature and recommendations for practice. J Thromb Haemostas pre-publication, 1-22-19 provides advice on how to measure extended half-life and B-domain-deleted factor concentrates VIII and IX. The article illustrates the wide variations in PTT-based one-stage clot-based assay results for the various new preparations related to the various reagent activators silica, kaolin, ellagic acid, or polyphenols. The writers show that the currently available chromogenic substrate factor VIII assays recover reasonably accurate results for all preparations. Chromogenic factor IX assays are approved for use in only a handful of locations but provide accurate measurement of factor IX concentrate therapy.

The article is accepted and will be published in a near future JTH issue.

The authors make a provocative statement about one of the extended half-life products. Here is a paraphrase.
For the FVIII-SC product, AFSTYLA, all PTT reagents led to decreased recoveries. The manufacturer recommends that the one-stage clot-based assay may assay the agent so long as the result is multiplied by a factor of 2. The US FDA allows this recommendation to be included in the package insert. The authors concur with other authors that doubling cannot be considered entirely safe, especially when an accurate chromogenic substrate approach is available. Lot-to-lot reagent variation may not yield the same results and the degree of reduced recovery, while averaging approximately 50%, varies between 30 and 70%. Therefore, for one reagent a recovery of 30% multiplied by 2 would give a “true” factor level of 60% while a recovery of 70% multiplied by 2 would give a “true” factor level of 140% so in some respects the multiplying factor could increase the difference between the true result and the observed result.

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A pre-publication article, Young G, Perry D, The International Prophylaxis Study Group (IPSG). Laboratory assay measurement of modified clotting factor concentrates: a review of the literature and recommendations for practice. J Thromb Haemostas pre-publication, 1-22-19 provides advice on how to measure extended half-life and B-domain-deleted factor concentrates VIII and IX. The article illustrates the wide variations in PTT-based one-stage clot-based assay results for the various new preparations related to the various reagent activators silica, kaolin, ellagic acid, or polyphenols. The writers show that the currently available chromogenic substrate factor VIII assays recover reasonably accurate results for all preparations. Chromogenic factor IX assays are approved for use in only a handful of locations but provide accurate measurement of factor IX concentrate therapy.

The article is accepted and will be published in a near future JTH issue.

The authors make a provocative statement about one of the extended half-life products. Here is a paraphrase.
For the FVIII-SC product, AFSTYLA, all PTT reagents led to decreased recoveries. The manufacturer recommends that the one-stage clot-based assay may assay the agent so long as the result is multiplied by a factor of 2. The US FDA allows this recommendation to be included in the package insert. The authors concur with other authors that doubling cannot be considered entirely safe, especially when an accurate chromogenic substrate approach is available. Lot-to-lot reagent variation may not yield the same results and the degree of reduced recovery, while averaging approximately 50%, varies between 30 and 70%. Therefore, for one reagent a recovery of 30% multiplied by 2 would give a “true” factor level of 60% while a recovery of 70% multiplied by 2 would give a “true” factor level of 140% so in some respects the multiplying factor could increase the difference between the true result and the observed result.

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