engleski

A PATIENT WITH FVIII INHIBITORS ON EMICIZUMAB PROPHYLAXIS SWITCHING TO IMMUNE TOLERANCE INDUCTION – LABORATORY ISSUES

Background/Aims: Novel hemostatic agent emicizumab has a huge influence on standard laboratory assays and can lead in a misleading interpretation of coagulation results in emicizumab-treated patients. As quantification of inhibitors is the prerequisite for the successful immune tolerance induction (ITI), when switching from emicizumab prophylaxis to ITI, laboratory follow-up must be adequate due to longterm effect of emicizumab. The study aimed to present laboratory long-term follow-up results of a 9-year-old boy with severe hemophilia A and inhibitors (historical peak 21 BU/mL), treated with emicizumab and switched to ITI. Materials and Methods: The boy received an emicizumab loading dose (3 mg/kg) once weekly for 4 weeks, followed by maintenance with lower doses (1.5 mg/kg) once weekly for 4 weeks. One month after the last dose, the boy was switched to ITI with daily administration of plasma-derived FVIII concentrate (Octanate 2500 IU/L). Laboratory follow-up included: aPTT (Actin FS), aPTT-based one-stage FVIII clotting assay with Actin FS (Siemens Healthcare Diagnostics, Marburg, Germany) and chromogenic FVIII activity assay with human reagents BIOPHEN FVIII:C (Hyphen BioMed, France). FVIII inhibitors were diagnosed using clot-based and chromogenicBethesda assay with bovine reagents on AtellicaCOAG360 analyzer(Siemens) and chromogenic Bethesda assay with human reagents on SysmexCS-2000i (Sysmex, Kobe, Japan). Results: Laboratory results obtained during a 4-month period (Table) showed remarkable shortening of aPTT results and high FVIII:C activities measured with clot-based assay up to 2 months after emicizumab discontinuation. Even low emicizumab activity (1.6 IU/dL) resulted in falsely low inhibitor titre (3.9 BU/mL) using clot-based assay, compared to chromogenic Bethesda assay with human and bovine reagents (57.6 and 58.9 BU/mL, respectively). Conclusions: Residual emicizumab activity after discontinuation needs to be taken into consideration when performing clot-based coagulation assays in further follow-up of patients. Regarding inhibitor testing, unlike clotting assay, , both chromogenic methods enabled reliable quantification.

emicizumab ; FVIII inhibitor ; chromogenic FVIII assay ; laboratory diagnosis

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