4662 Replacement therapy is a very hard challenge in haemophilia B with inhibitor. We describe the case of a child with severe haemophilia B and with a family history positive for development of inhibitor to factor IX (FIX) and for occurrence of allergic reaction after replacement therapy. Genetic analysis demonstrated an almost complete deletion of FIX gene. The child received replacement therapy first in his life when he was 5 years old because of the occurrence of a large haematoma of the left thigh. He was treated with recombinant FIX concentrate at the dosage of 30 IU/kg daily for three days and no inhibitor to FIX was evidenced after this therapy. Two months later the patient was treated with a single dose of recombinant FIX concentrate at the same dosage for the occurrence of a post-traumatic joint bleeding of the right knee. An inhibitor towards FIX (1.7 B.U.) was detected two weeks after this treatment and confirmed in a subsequent analysis performed after ten days (1.4 B.U.). One month later the patient was hospitalized for a post traumatic hemarthrosis of the right shoulder. In this occasion it was planned to treat the patient with recombinant FIX under careful monitoring in intensive care unit considering of the inhibitor. After the slow endovenous infusion of 200 IU of recombinant FIX concentrate we stopped immediately the administration because the child presented cough, mild respiratory failure, tachycardia, tongue and lips oedema, lips cyanosis, diffuse vasodilatation, psychomotor agitation. He received also hydrocortisone, antihistaminic by intramuscular injection and oxygen by facial mask. The presence of inhibitor towards FIX and anaphylactic reaction occurrence preclude forever any replacement therapy with FIX both recombinant and plasmatic (PCC and/or aPCC). After this episode the patient needed another hospitalization for a tonsil bleeding with severe anaemization. We treat him with recombinant activated FVII (rFVIIa) first at the dosage of 270 mcg/kg in bolus, and after at the dosage of 90 mcg/kg every three hours for one day with complete bleeding remission. We encourage the careful monitoring of inhibitor towards FIX in haemophilic B patients especially with large FIX gene deletion. It could prevent severe anaphylactic reaction during replacement therapy. Considering the previous anaphylactic reaction, in this child rFVIIa represents the only therapeutic option for bleeding management. Disclosures: No relevant conflicts of interest to declare.

The authors report a case of hemarthrosis complicated by severe anemia related to a congenital connective tissue disease: Ehlers-Danlos syndrome. A boy fell down and suffered tumefaction of both knees with bilateral rupture of the rotula tendon. He underwent surgical reinsertion of each tendon on the rotula. He later showed an unexpected ongoing hematic effusion, with severe anemia. He was screened for coagulation disorders with no results. On taking a more detailed history and investigating the patient's phenotypical features, the authors diagnosed Ehlers-Danlos syndrome, hypermobile variant. The hemarthrosis and anemia were thus concluded to be consequences of excessive tissue fragility due to a congenital connective tissue disease.

4660 One of the serious complication in hemophilia therapy is the development of high titre inhibitors to FVIII and less often to others coagulation factors. It makes treatment of bleeds very challenging. We report a case of hemarthrosis in hemophilia A pediatric patient with inhibitors, treated with sequential infuson of rFVIIa (rFVIIa, NOVOSEVEN; Novo Nordisk A/S, Bagsvaerd, Denmark) and plasma activated prothrombin complex concentrate (pd- aPCC, FEIBA; Baxter AG Vienna Austria). rFVIIa and plasma activated prothrombin complex concentrate are, indeed, used as haemostatic bypassing agents to prevent eaemorrages, with the goal of limiting sequelae as arthropathy, or to control quickly heamostasis as intensive on–demand treatment. A 3 years old male patient affected by haemophilia A with inhibitors came to our observation for a traumatic hemarthrosis of the left knee. Clinic examination showed swelling and pain. His inhibitor titre was 29 Bethesda Units. First we infused rFVIIa for seven consecutive days at the dose of 90 ug/kg every 3 hours. This therapy didn't determinate any clinical improvement. Then we infused plasma activated prothrombin complex concentrate for the next consecutive seven days at the dose of 60 UI/kg every 12 hours. At the end of treatment we noticed pain disappearance and reducing swelling. Medical literature recently describes similar paediatric cases treated with sequential infusion of rFVIIa and plasma activated prothrombin complex concentrate. Our positive experience could stimulate to use haemostatic bypassing agents because apparently safe. We encourage to use this therapeutic scheme because it seem to reduce healing times of acute events. Disclosures: No relevant conflicts of interest to declare.