Abstract Number: PB0636
Meeting: ISTH 2020 Congress
Background: Quantification of modified coagulation factor VIII (FVIII), and the bifunctional monoclonal emicizumab (emi), in coagulation tests is complicated.
Aims: We evaluated a modified APTT for quantification of emi and the effects in clot growth analysis as pharmacodynamic model.
Methods: APTT with the STA and clot growth with Thrombodynamics. Commercial factor VIII, Haemate, and FVIII-deficient patient plasmas were used. Samples from three emi-treated patients were from the Stasey study (Roche).
Results: A modified APTT- based one-stage FVIII assay using advanced dilutions, showed a dose response curve of Haemate that paralleled a dose response curve of emi in FVIII deficient patient plasma: 1 U/ml FVIII was equivalent to 30-35 µg/ml emi. Importantly, FVIII deficient plasma supplemented with 50, 100 and 150 % of recombinant FVIII as well as normal plasma, showed parallel curves for added emi and no contribution of FVIII in the assay. Thus, emi completely dominates the assay and can be quantified, also in the presence of FVIII. In three F VIII deficient patients treated with emi we detected no emi in the pre-treatment sample < LLOQ) and 56-66, 55-51 and 40-43 µg/ml emi in samples after 1- and 3-month protocol treatment.
In clot growth analysis correction with FVIII showed a non-linear response with a steep increase at low levels: 80% of correction was achieved at 0.2 U/ml Factor VIII. Emi showed a congruent pattern with 80% correction at 20 µg/ml emi. Analysis of clot growth in plasma of two patient treated with emi showed clot growth normalisation at 1- and 3-month treatment.
Conclusions: In vitro spiking in clot growth gave 80% correction with emi at relatively low concentrations (20 µg/ml). The APTT- based assay showed equivalence with I U/ml Factor VIII at 30-35 µg/ml. Both evaluations suggested adequate effects at lower emi concentrations than currently used in patient treatment.
To cite this abstract in AMA style:Kluft C, van Leuven K, Talens S, Klip N, Szanto T, Lassila R, Karamzin S, Ataullakhanov F. Quantification of Emicizumab in a Modified APTT and with Clot Growth Analysis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/quantification-of-emicizumab-in-a-modified-aptt-and-with-clot-growth-analysis/. Accessed November 27, 2021.
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