title: Recombinant factor VIIa in the management of surgery and acute bleeding episodes in children with haemophilia and high-responding inhibitors.
abstract: The development of inhibitors to therapeutic factor concentrates in children with haemophilia A or B is a troublesome complication of factor replacement therapy. Immune tolerance protocols have been developed to eliminate the inhibitors, and these are successful in approximately 80% of children. However, acute bleeding episodes require treatment with a factor (F)VIII or FIX bypassing agent to prevent an anamnestic rise in the inhibitor level before starting immune tolerance. In addition, central venous access is necessary to help parents administer frequent, high dose factor concentrate. In view of the benefits of rFVIIa seen in adults, a study has been carried out on the use of this agent as haemostatic cover in children with severe FVIII or FIX deficiency with high responding inhibitors. Information was obtained retrospectively from the National Children's Hospital, Dublin and Great Ormond Street Hospital, London. Twelve children aged 1-16 years were treated successfully with rFVIIa to prevent surgical bleeding in 20 surgical procedures. Minor post-operative haematomata developed in 2 of 20 cases after regular rFVIIa therapy had been discontinued. In both cases, resolution of bleeding occurred after a short course of rFVIIa. Three children experienced a total of six life- or limb-threatening bleeds. All bleeding episodes resolved with regular rFVIIa treatment, although topical fibrin glue was needed in one child with a frenulum tear. The rFVIIa therapy was well tolerated and there was no evidence of any treatment-related complications. In conclusion, rFVIIa is the treatment of choice for the management of surgery and acute life- or limb-threatening bleeding in children with haemophilia and high responding inhibitors.
authors.affiliation: National Centre for Hereditary Coagulation Disorders, The National Children's Hospital, Dublin, Ireland. osmith@stjames.ie
authors.forename: Owen P
authors.initials: OP
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D001779:Blood Coagulation Factors / Q000276:immunology; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D005167:Factor VII / Q000008:administration & dosage* / Q000009:adverse effects; D015942:Factor VIIa; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy* / Q000276:immunology*; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007223:Infant; D007518:Isoantibodies / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D013514:Surgical Procedures, Operative; D016896:Treatment Outcome
chemical_list: D001779:Blood Coagulation Factors; D007518:Isoantibodies; D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa