Case n.1
A 14 year old boy with severe haemophilia A developed inhibitor after 14 exposure days to an antigen (rFVIII, ADVATE® Baxter Healthcare, Zurich, Switzerland)[15]. He received Immune tolerance induction (ITI) with FVIIIs (ADVATE® , pdF VIII FACTANE®,Laboratoire Français du Fractionnement des Biotechnologies (LFB), Les Ulis, France; OCTANATE®, Octapharma AG, Lachen, Switzerland). Last inhibitor titer was 22.8 UB/mL. He received BPA (FVIIa and activated prothrombin complex concentrate (aPCC)) for bleeding and prophylaxis, his Annual Bleeding Rate (ABR) stay at 12. Emicizumab was started at 13 years old : initiation phase with 3 mg/kg/week the first 4 weeks followed by stabilisation phase with 1.5 mg/kg/week[9]. During initiation phase, TG (endogenous thrombin potential (ETP) and Peak) was measured just before emicizumab injection (Table 1). Before the 4th 3mg/kg dose, residual ETP was 1041 nM*min and Peak was 50.1 nM. 4 weeks after stabilisation phase, ETP and Peak (6 days after injection) were lower than previously (895 nM*min and 39.7 nM) (Table 2) and lower than normal defined in 40 healthy volunteers. We decided to add Novoseven® for surgery. To assess which dose of FVIIa would provide safe bleeding protection, different concentrations of Novoseven® were evaluated in vitro by TGA in platelet-rich plasma (PRP)[13]. We spiked patient PRP collected 6 days after 1.5 mg/kg emicizumab injection with different Novoseven®concentrations (Table 2). In vitro, with 45 µg/kg of Novoseven® , ETP was normalized (1159 nM*min) ; with 90 µg/kg ETP was normalized (1219 nM*min) and we had a better response for Peak (54.5 nM). We chose 45 µg/kg for surgery as ETP was in normal range.
After 10 weeks of emicizumab, central catheter (Broviak type) was removed. We perfused 45 µg/kg of Novoseven® 30 minutes before surgery. On surgery day, TG at basal was performed 5 days after 1.5 mg/kg emicizumab injection (ETP 796.48 nM*min, Peak 36.12 nM) and were lower than previously. TG measured ex vivo after rVIIa infusion the day of surgery was lower than in vitro after rVIIa spiking (Table 2). Surgery went safely.