Immune tolerance induction with a high-purity von Willebrand factor containing plasma-derived factor VIII concentrate in a child with hemophilia A with inhibitors

Abstract

Immune tolerance induction (ITI) is the principal method of inhibitor eradication in patients with hemophilia A. The existing guidelines generally recommend to start ITI with recombinant FVIII concentrates, but the presence of VWF in plasma-derived FVIII concentrates used for ITI may further influence the ITI success rate. A five-year-old male patient with hemophilia A withinhibitors started ITI at our Center. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications. The patient had an inhibitor titer of 0.52 BU/mL at the start of the ITI and a historical inhibitor peak titer of 28 BU/mL. The ITI was started 3.5 years after the first inhibitor detection. We chose a plasma-derived VWF/FVIII containing concentrate (Haemate P) and started the ITI at a dose of 100 units FVIII/kg once per day using central venous access, as proposed in the protocol developed by the United Kingdom Haemophilia Centre Doctors’ Organization (UKHCDO). The inhibitor titer rose to 5.5 BU/mL on day 10 and became negative on day 25 of the ITI. The FVIII trough level measured 24 h after the last dose was > 1 % on day 25. The patient discontinued prophylaxis with a bypassing agent. However, FVIII pharmacokinetics had not returned to normal yet, and the patient continued the ITI with the VWF/FVIII containing concentrate at the initial dose. We reassessed the parameters of FVIII pharmacokinetics 120, 270 and 300 days after the start of the ITI. The peak FVIII level, its half-life time and the trough level measured 24 h after the last dose gradually increased over time. On day 300, the half-life time was still less than 7 h (6 h), but the trough level at 24 h was as high as 12.6 %. So, the patient started tapering off the medicine (the dose was initially reduced to 75 units/kg once per day). No adverse events were observed during the 1 year of therapy. Starting from day 423, the patient was switched to prophylaxis with the concentrate administered at a dose of 50 IU/kg every other day. Here, we reported our experience with first-line ITI using the FVIII concentrate with a high content of VWF (Haemate P). A rapid decrease in the inhibitor titer and the normalization of the pharmacokinetic parameters of FVIII in the absence of significant bleeding or thrombotic complications were convincingly demonstrated.