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• W2053019324 abstract "Published guidelines on the management of patients with autoimmune idiopathic thrombocytopenic purpura (AITP) fail to make recommendations for the subset of patients with platelet counts < 30 × 109/l and persistent bleeding despite standard treatment (George et al, 1996). We report here the successful treatment of a paediatric patient with recombinant Factor VIIa (rFVIIa; NovoSeven®, NovoNordisk, Copenhagen, Denmark). An 8-year-old girl with a 3-year history of AITP presented with epistaxis. On admission, her platelet count was 3 × 109/l and haemoglobin was 7·4 g/dl. Serum iron was 7·9 µmol/l, unbound iron-binding capacity 82 µmol/l, total iron-binding capacity 90 µmol/l and ferritin < 3 µg/l. Prothrombin time, partial thromboplastin time and plasma fibrinogen concentration were all normal. Intravenous immunoglobulins were contraindicated because of a previous severe allergic reaction, so she was managed with a deep nose tampon, corticosteroids, erythrocyte transfusions and tranexamic acid. The patient had a second brief episode of epistaxis at 24 h that stopped spontaneously, but otherwise did well initially. On d 9, epistaxis recurred, accompanied by severe headache. Her platelet count was 13 × 109/l, fibrinogen 0·8 g/l and FXIII 51 iu/dl. The other coagulation parameters were normal. Initial management with a deep nose tampon, corticosteroids, platelet transfusions (6 units) and tranexamic acid was ineffective, and her condition deteriorated until she received an intravenous bolus injection of 85 µg/kg rFVIIa. Bleeding subsequently decreased within a few minutes and stopped within 1 h. Her headache resolved with no neurological deficit. Despite treatment with corticosteroids and tranexamic acid, the patient presented on d 30 with severe incessant epistaxis. Her haemoglobin was 9·1 g/dl, and her platelet count was 13 × 109/l. She received platelet transfusions (4 units) and a deep nose tampon with no effect. The bleeding stopped 1 h after a single bolus injection of 85 µg/kg rFVIIa. At d 34, she was stable with a platelet count of 13–42 × 109/l. There was no further bleeding. No adverse effects were observed; FXIII and fibrinogen levels were normal. rFVIIa represents a rational management approach to bleeding complications resulting from platelet disorders (Hedner, 1998; Negrier & Lienhart, 2000), but we believe that this is the first reported use in a child with AITP. At physiological concentrations, FVIIa initiates haemostasis through its interaction with tissue factor (TF) at the site of injury, forming a catalytically active complex. The TF/FVIIa complex leads to the activation of FX and, thus, to the formation of small amounts of thrombin, leading in turn to the activation of coagulation Factors VIII, V, XI and platelets. At the higher concentrations found after therapeutic administration, FVIIa also binds directly to activated platelets to initiate thrombin formation. Platelet-bound FVIIa in higher concentrations is functionally active and initiates thrombin formation via direct activation of FX. This pathway is independent of the presence of TF (Monroe et al, 1997). Infusion of rFVIIa has been shown to reduce or stop bleeding in patients with thrombocytopenia, and high doses may help to provide haemostasis in these patients by increasing the initial thrombin generation (Kristensen et al, 1996; Kjalke et al, 2001). We suggest that, in this patient, the dual action of rFVIIa played a crucial role in maximizing platelet activation and thrombin generation. We conclude that rFVIIa provided safe and effective therapy for severe bleeding in a child with AITP who was unresponsive to other therapy. As there is currently a lack of consensus about how such patients should be managed, this approach should be studied further." @default.
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• W2053019324 date "2003-03-01" @default.
• W2053019324 modified "2023-10-15" @default.
• W2053019324 title "Recombinant factor viia for refractive haemorrhage in autoimmune idiopathic thrombocytopenic purpura" @default.
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• W2053019324 doi "https://doi.org/10.1046/j.1365-2141.2003.04151_2.x" @default.
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