Assessing the Performance of Extended Half-Life Coagulation Factor VIII, FC Fusion Protein by Using Chromogenic and One-Stage Assays in Saudi Hemophilia A Patients

Abstract

Background. The one-stage assay is the most common method to measure factor VIII activity (FVIII : C) in hemophilia A patients. The chromogenic assay is another two-stage test involving purified coagulation factors followed by factor Xa-specific chromogenic substrate. Aim. This study aimed to assess the discrepancy and correlation between the chromogenic and one-stage assays in measuring FVIII : C levels in hemophilia patients receiving Extended Half-Life Elocta® as a recombinant extended half-life coagulation factor. Methods. We performed a study comparing the measurements of FVIII : C levels by the chromogenic versus the one-stage assays at different drug levels. Data of FVIII : C levels, dosage, and the time interval from administration to measurement were retrieved from the hospital records. The correlation, mean differences, and discrepancy between the two assays were calculated. The linear regression analysis was used to predict the time interval till reaching 1% FVIII : C. Results. Fourteen patients with 56 samples were included in the study. Of them, 13 patients were receiving Elocta® as a prophylactic, while one was receiving Elocta® on demand. One-third of these samples showed a discrepancy between the chromogenic and one-stage assays. The two assays were well correlated. Mean differences were significant at the individual and the time interval level. The time since the last Elocta® injection could significantly predict FVIII : C levels (β = 0.366, P<0.001). Conclusion. Our findings suggested a significant difference between both methods; the FVIII : C levels measured by the one-stage assay were less than those estimated by the chromogenic assay. However, the measurements of FVIII levels by the two assays were well correlated but discrepant in one-third of the samples. The levels of FVIII : C reach 1% after 5.4 days since the last Elocta® administration.

Comparison of one‐stage and chromogenic factor VIII assays to tailor the dose of recombinant factor VIII‐Fc fusion protein (rFVIIIFc, efmoroctocog alfa) in adult patients with haemophilia A: Single‐centre, real‐world experience of surgery

“…Despite this discrepancy, it was concluded that these two assays could be used, without the need for a product‐specific standard, to monitor rFVIIIFc 8 . That higher FVIII levels are measured with CSA compared to OSA has also been confirmed by Owaida et al 9 . The BIMHO group published French national guidelines for biological monitoring of rFVIII.…”

Plasma Clearance of Coagulation Factor VIII and Extension of Its Half-Life for the Therapy of Hemophilia A: A Critical Review of the Current State of Research and Practice

“…Early studies reported the OC/CS assay ratio as ~0.9 for rFVIII-Fc activity measurements [94,95], whereas in subsequent studies, it was as low as ~0.5 for some reagents combinations and some patients' plasma samples [96][97][98]. Similar OC/CS ratios were found for other BDD-FVIII-based variants: turoctocog alfa, simoctog alpha, and moroctocog alfa [87,97]. This indicates that all BDD-FVIII variants may show such discrepancy, though particular assay setups may minimize it.…”

An Update on Laboratory Diagnostics in Haemophilia A and B

“…43 In contrast to the OSCA results, higher results for rFVIIIFc are obtained when samples are analysed by CSAs. 35,[42][43][44] It was assumed that these discrepancies stem from differences between the WHO IS for FVIII concentrate or plasma. 42 However, it is generally concluded that both the OSCA and the CSA may be used to safely monitor rFVIIIFc-based factor FVIII replacement therapies.…”