title: Rationale for the use of high dose rFVIIa in a high-titre inhibitor patient with haemophilia B during major orthopaedic procedures.
abstract: Inhibitor development is a serious complication in patients with haemophilia A and B. Historically, a lack of optimal therapies and factor products for treating inhibitor patients resulted in many patients developing chronic haemophilic arthropathies and flexion contractures of the involved joints. The introduction of immune-tolerance protocols to eradicate high-titre inhibitors has greatly diminished the incidence of these types of complications but as in the case reported here, immune tolerance is not always successful. Various elective surgical procedures were often delayed or not even considered in patients with inhibitor because of the variability in achieving adequate haemostasis and the thrombotic risks involved with the use of activated prothrombin-complex concentrates (APCCs) over extended periods of time. The development of recombinant factor VIIa (rFVIIa; NovoSeven) and its demonstrated safety and efficacy in treating inhibitor patients has opened new possibilities for addressing severe arthropathy with flexion contracture. This case report demonstrates that the use of rFVIIa in such a situation must include dosing flexibility that is both patient-specific and related to the potential for bleeding; the ability to maintain clinical haemostasis with a prophylactic dose of rFVIIa given as little as once daily; and the capacity for higher doses of rFVIIa, particularly in children because their kinetic profiles differ from adults.
authors.affiliation: Department of Paediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7220, USA.hcooper@med.unc.edu
authors.forename: H A
authors.initials: HA
authors.lastname: Cooper
authors.forename: C P
authors.initials: CP
authors.lastname: Jones
authors.forename: E
authors.initials: E
authors.lastname: Campion
authors.forename: H R
authors.initials: HR
authors.lastname: Roberts
authors.forename: U
authors.initials: U
authors.lastname: Hedner
mesh_terms: D000293:Adolescent; D016063:Blood Loss, Surgical / Q000517:prevention & control; D004200:Diseases in Twins; D005167:Factor VII / Q000008:administration & dosage*; D015942:Factor VIIa; D002836:Hemophilia B / Q000188:drug therapy / Q000276:immunology / Q000601:surgery*; D006801:Humans; D007108:Immune Tolerance; D007518:Isoantibodies / Q000097:blood; D008297:Male; D009985:Orthopedics; D011994:Recombinant Proteins / Q000008:administration & dosage*
chemical_list: D007518:Isoantibodies; D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa