Measurements of eftrenonacog alfa by 19 different combinations reagents/instrument: A single‐centre study. Issue 3 (20th April 2020)

• Record Type: Journal Article
• Authors: Sinegre, Thomas; Trayaud, Adeline; Tardieu, Maryse; Fourneyron, Virginie; Talon, Laurie; Berger, Marc G.; Tillier, Maxence; Senectaire, Stéphanie; Gembara, Piotr; Barbin, Anne‐Lise; Vaissade, Aurélie; Lebreton, Aurélien
• Is Part Of: Haemophilia. Volume 26:Issue 3(2020)
• Page Start: 543
• Page End: 552
• Publication Date: 2020-04-20
• Subjects: chromogenic assay -- clotting assay -- eftrenonacog alfa -- factor IX -- Fc fusion -- haemophilia; Hemophilia -- Periodicals; 616.1572005
• DOI: 10.1111/hae.14003
• Languages: English
• ISSNs: 1351-8216

Abstract

Abstract: Introduction: Recombinant factor IX Fc fusion protein (rFIXFc) is an extended half‐life concentrate for the treatment of haemophilia B (HB). rFIXFc activity monitoring is crucial in several clinical situations. However, differences were observed between one‐stage clotting (OSC) and chromogenic assays, but not for all factor IX (FIX) concentrations. Aims: To compare rFIXFc measurements obtained using different instruments and common OSC and chromogenic asssays. Methods: FIX:C measurements were performed in rFIXFc‐spiked plasma aliquots (targeted FIX levels of 1.5, 1, 0.5, 0.2, 0.05, 0.02 and 0.01 IU/mL) and plasma samples collected from two patients with HB at various time points after rFIXFc infusion, using three instruments (STA‐R MAX, ACLTOP700 and CS2100i) and common clotting and chromogenic FIX:C assays. Results: The same reagent could give different FIX:C measurements when adapted to different instruments. Moreover, the same reagent/instrument combination could give different results depending of the FIX concentration. For OSC assays, only STA‐Cephascreen on STA‐R MAX and CS2100i, SynthAFax on ACLTOP 700 and Actin on CS2100i provided acceptable recoveries for all rFIXFc concentrations. The chromogenic assays ROX‐FIX and Biophen FIX:C underestimated rFIXFc for concentrations lower than 0.05 and 0.2 IU/mL, respectively. Conclusions: Our study demonstrates that the same reagent adapted to different instruments could lead to different rFIXFc values. As rFIXFc under/overestimation could be associated with inappropriate treatment or biased calculation of pharmacokinetic parameters, the reagent/instrument combination used by haemostasis laboratories should be considered and regularly evaluated by external quality assessment programmes.