C0397 Thromboembolitic events in patients with systemic vasculitis

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Background: Thrombin generation (TG) has been previously shown to be correlated to the haemorrhagic phenotype observed in acquired haemophilia (Millet 2001). In a patient with acquired haemophilia, we have followed over 8 months, the evolution of different parameters of the TG test (TGT), in parallel with the anti FVIII inhibitor level. The in vitro response to the addition of NOVOSEVEN was also tested. Patient: An 87 years-old woman was admitted in an intensive care unit for digestive haemorrhage and severe anaemia (Hb 0.59 g/dL)in relation to hiatal hernia and digestive ulceration (treated by clips, IPP and blood transfusion). One month later, she presented hematoma of both arms and face, and echymotic purpura of the leg. The Hb level was 0.66 g/dL. Blood coagulation: PT 94%,aPTT ratio 3,19, Fibrinogen 1,6 g/L, Rosner Index at 25 and 52 respectively at T=0 and T=2 h, dRVVT ratio 0,99, FVIII:C level b1% and anti FVIII inhibitor at 64 Bethesda Units (BU). Under MABTHERA (375 mg/m2) (once a week over 5 weeks), a progressive correction of the anti FVIII inhibitor was observed. Methods: Blood samples have been regularly taken during the following. The inhibitor level was regularly measured (Bethesda Units). TGT was evaluated with the Calibrated Automated Thrombogram (CAT), using endogenous reagent (cephalin) or exogenous reagent (PPP reagent low, Stago, containing 1 pM tissue factor and 4 μM phospholipids final), in absence or presence of increased concentrations of NOVOSEVEN. Each plasma was tested in duplicate. Results: The anti-FVIII antibody inhibited the TG using either the endogenous and exogenous pathway, in correlation with the anti FVIII inhibitor level. In vitro, ,the addition of increasing doses of NOVOSEVEN is associated with a partial correction whatever the reagent used; however the correction of the inhibition of the TG is NOVOSEVEN-dose dependentwith the cephalin reagent and non dose dependentwith the PPP reagent low, the correction reaches a plateau. Comment: The evolution of the different parameters of the TG under MABTHERA, allowed the estimation of the bleeding tendency of a patient, in parallel with the anti FVIII inhibitor level, with both activator reagents. The TG, using cephalin reagent, could allow to evaluate the capacity of NOVOSEVEN to improve TG in patient's plasma. The use of this TGT with the endogenous pathway, in patients treated with NOVOSEVEN, remains to be investigated.