Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia.

BACKGROUND: Effective ways to prevent arthropathy in severe hemophilia are unknown. METHODS: We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI). RESULTS: Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P=0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups. CONCLUSIONS: Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597 [ClinicalTrials.gov].).

Successful treatment of acquired factor VIII deficiency in a child using activated factor VII concentrates: case report and review of the literature.

Acquired factor VIII deficiency is a rare life-threatening disorder that should be suspected in individuals without a prior bleeding history who present with mucous membrane, muscle, and/or urinary tract bleeding. The authors describe a 5-year-old girl with epistaxis, intramuscular bleeding, and forearm compartment syndrome requiring emergent fasciotomy. Coagulation studies showed a factor VIII level of less than 1%. The prolonged activated partial thromboplastin time corrected immediately when mixed with normal plasma at a 1:1 ratio but became prolonged again following incubation at 37 degrees C. She was treated successfully with serial administrations of activated factor VII concentrates and immunosuppression with corticosteroids. Activated factor VII concentrates should be considered as an option for patients of all ages with acquired factor VIII deficiency.