Factor VIII and IX assays for post‐infusion monitoring in hemophilia patients: Guidelines from the French BIMHO group (GFHT)

Abstract

Replacement therapy with plasma‐derived or recombinant FVIII and FIX (pdFVIII/pdFIX or rFVIII/rFIX) concentrates is the standard of treatment in patients with haemophilia A and B, respectively. Measurement of factor VIII (FVIII:C) or factor IX (FIX:C) levels can be done by one‐stage clotting assay (OSA) or chromogenic substrate assay (CSA). The French study group on the Biology of Hemorrhagic Diseases (a collaborative group of the GFHT and MHEMO network) presents a literature review and proposals for the monitoring of FVIII:C and FIX:C levels in treated haemophilia A and B patients, respectively. The use of CSA is recommended for the monitoring of patients treated with pdFVIII or rFVIII including extended half‐life (EHL) rFVIII. Except for rFVIII‐Fc, great caution is required when measuring FVIII:C levels by OSA in patients substituted by EHL‐rFVIII. The OSA is recommended for the monitoring of patients treated with pdFIX or rFIX. Large discordances in the FIX:C levels measured for extended half‐life rFIX (EHL‐rFIX), depending on the method and reagents used, must lead to great attention when OSA is used for measuring FIX:C levels in patients substituted by EHL‐rFIX. Data of most of recent studies, obtained with spiked plasmas, deserve to be confirmed in plasma samples of treated patients.

Impact of aPTT reagents on measurement of a PEGylated recombinant FVIII (Adynovi®/Adynovate®): A French multicentric field assay study

“…The complexity of the silica types as well as the composition of the phospholipids makes all aPTT reagents very different. 12 In conclusion, this multicentre study shows that chromogenic…”

“…The data that support the findings of this study are available from the corresponding author upon reasonable request. Claire Pouplard 11,12 the French study group on laboratory management of bleeding disorders (BIMHO Group-GFHT)…”

The Evaluation of APTT Reagents in Reference Plasma, Recombinant FVIII Products; Kovaltry® and Jivi® Using CWA, Including sTF/7FIX Assay

“…Recently, the presence of marked inter-laboratory variability in the results obtained using APTT peak time-based assays, which can be intensified in a reagent-specific manner depending on the EHL-FVIII used, has attracted attention. [15][16][17][18] The use of a chromogenic substrate assay, which tends to show less variability, especially with EHL-FVIII, is therefore recommended. 19,20 However, the one-stage APTT peak time-based method is widely used and more easily performed in small laboratories than the chromogenic substrate assay.…”

“…The relationship between various APTT reagents and normal half-life-(NHL-) and EHL-FVIII has been described in several reports using a routine APTT assay based on the peak times of a CWA and chromogenic substrate assay. [16][17][18] However, few reports have described this relationship using the peak height of an APTT-CWA including a sTF/FIX assay. 9 An APTT-CWA may be able to reveal the differences among various APTT reagents, as the differences in APTT-CWA results may be greater in patients with lower concentrations of FVIII than in those with higher concentrations.…”

Factor VIII and Factor IX Activity Measurements for Hemophilia Diagnosis and Related Treatments

“…66,91 In 2020, there were three guidance publications that provided recommendations for or against FVIII and FIX OSA or CS assays for EHL products. 68,92,93 Of particular concern is (1) limited data for nondescribed aPTT reagents, (2) insufficient or discordant data obtained from clinical or field studies, and (3) discordant OSA or CSA recommendations between these publications. It is likely that a clinical laboratory will provide a single OSA method for both FVIII and FIX, usually due to contractual agreements or instrument default methods.…”