title: Sequential combined bypassing therapy is safe and effective in the treatment of unresponsive bleeding in adults and children with haemophilia and inhibitors.
abstract: Some 10-20% of bleeding events in haemophilia patients with high-responding inhibitors cannot be controlled with bypassing agents. However, sequential combined bypassing therapy (SCBT) has been reported to be successful in five children. To extend this observation, a survey was undertaken by the European Haemophilia Treatment Standardisation Board (EHTSB) in children and adults. Data were collected from all centres belonging to the EHTSB network by a retrospective medical record review. SCBT courses were defined as the administration of both recombinant activated factor VIIa (rFVIIa) and activated prothrombin complex concentrate (APCC) within 12 h. A web-based database was prepared to collect data on SCBT courses in a standardized and anonymous manner from patients' files. Eleven inhibitor patients underwent SCBT (nine haemophilia A; two haemophilia B). Two children had refractory knee haemarthrosis and one, an unresponsive calf haematoma. Five adults had significant bleeds following major surgery, one had lower limb compartmental syndrome and one a post-traumatic upper limb haematoma and haemarthrosis. SCBT administration alternated one APCC dose to 1-3 rFVIIa doses: dosing intervals ranged between 3 and 6 h; APCC (20-80 U kg(-1) ) was given every 8-12 h; rFVIIa (90-270 μg kg(-1) ) was given every 3-12 h. Bleeding control was achieved in 12-24 h in all patients. SCBT was discontinued after 1-15 days. No clinical adverse events were observed, but a significant increase in D-dimer levels was seen in three/five patients who were assessed. SCBT was efficacious without adverse events; nevertheless, due to potential risks, it remains a salvage treatment. A prospective clinical trial is needed to provide further evidence.
authors.affiliation: Department of Medical Specialities, University of Milan, Milan, Italy. alessandro.gringeri@unimi.it
authors.forename: A
authors.initials: A
authors.lastname: Gringeri
authors.forename: K
authors.initials: K
authors.lastname: Fischer
authors.forename: A
authors.initials: A
authors.lastname: Karafoulidou
authors.forename: R
authors.initials: R
authors.lastname: Klamroth
authors.forename: M F
authors.initials: MF
authors.lastname: López-Fernández
authors.forename: E
authors.initials: E
authors.lastname: Mancuso
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D002648:Child; D004359:Drug Therapy, Combination; D015942:Factor VIIa / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000601:surgery; D002836:Hemophilia B / Q000188:drug therapy* / Q000601:surgery; D006488:Hemostasis, Surgical / Q000379:methods; D006801:Humans; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; C025667:prothrombin complex concentrates; C103587:recombinant FVIIa; D015942:Factor VIIa