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.