Background: Emicizumab (EMI) is a recombinant, humanized bi-specific antibody that mimicking the cofactor function of FVIII. Although the use of EMI does not require routine laboratory monitoring, there are clinical situations (e.g. critical bleeding) when evaluation of the patient’s hemostatic status may prove useful. EMI therapy interferes with standard coagulation tests and makes laboratory monitoring challenging.

Aims: To investigate the role of thrombin generation assay (TGA) in monitoring the hemostatic potential of emicizumab in hemophilia A patients.

Methods: We analyzed 50 plasma samples from 13 hemophilia A (including 8 with FVIII inhibitor) patients on emicizumab. All patients samples were collected in steady state, just before the next dosage. Laboratory work-up included plasma emicizumab concentration (using a modified one-stage Factor VIII assay on the BCS XP analyzer [Siemens®] with an emicizumab-specific calibrator and controls [r²Diagnostics]) and TGA determined in platelet-poor plasma  on Ceveron®alpha with RC low reagent (Technoclone®). The patients’ TGA results were compared with those in two control groups [43 patients (aged 18-79) with confirmed mild hemophilia A (MHA) and 21 healthy male (aged 21-63)].

Results: Individual patient EMI concentration were within the range 26.6±2.41 to 67.1±6.16µg/mL.  Mean TGA peak thrombin (TGA-pt) was lower in EMI patients than in healthy controls (42.70±1.70 vs 92.20±11.74, respectively) while it was comparable to the TGA-pt results of the MHA patient group (42.70±1.70 vs 43±11.74nM, respectively). In the sample with the lowest concentration of EMI (24.1µg/mL) TGA-pt was 31.6nM and in the sample with the highest concentration (73.5µg/mL) – 46.00nM. No breakthrough bleeds was reported in patients during our study.

Conclusions: TGA seems to be a useful laboratory tool in monitoring of EMI therapy. Peak thrombin parameter is particularly useful in evaluating hemostasis in patients on EMI prophylaxis. There was positive correlation between EMI concentration and TGA-pt.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/results-of-thrombin-generation-assay-in-patients-treated-with-emicizumab/