title: A retrospective study of Octaplex in the treatment of bleeding in patients with haemophilia A complicated by inhibitors.
abstract: The nonactivated prothrombin complex concentrate (PCC) Octaplex (Octapharma PPGmbH, Vienna, Austria) has been used successfully for the treatment of congenital and acquired coagulation factor deficiencies and associated bleeding. The aims of this study were to assess retrospectively whether Octaplex is an effective treatment option for haemophilia A patients with high-titre inhibitors of factor VIII (FVIII) and to investigate the impact of Octaplex on thrombin generation in vitro and ex vivo. Retrospective data were collected from 15 haemophilia A patients with FVIII inhibitors who had been treated with Octaplex. Mild bleeds were treated for a median of 1 day with a median dose of 77 IU/kg and moderate bleeds for 3 days with 57 IU/kg. The physician's overall satisfaction with Octaplex, taking into account efficacy, safety and cost in comparison with other treatment options, was assessed for each bleed. The overall rating was good, very good or excellent for 29 of 41 (71%) bleeds. No adverse drug reactions were reported. In in-vitro studies of thrombin generation with normal plasma samples, experimental inhibition of FVIII activity prolonged the lag phase, diminished the peak thrombin concentration and decreased the area under the concentration-time curve, as expected. Marked improvement in thrombin generation parameters was achieved by adding 0.5-3 IU factor IX/ml PCC into the samples. The same held true when using plasma samples from haemophilia A patients with FVIII inhibitors. These results demonstrate that Octaplex overcomes inhibition of FVIII in in-vitro and ex-vivo assays of thrombin generation, and that Octaplex is an effective treatment option for haemophilia A patients with FVIII inhibitors.
authors.affiliation: Centre for Thrombosis and Haemostasis, Skane University Hospital, Lund University, Malmö, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Berntorp
authors.forename: Sandra
authors.initials: S
authors.lastname: Figueiredo
authors.forename: Lucimara
authors.initials: L
authors.lastname: Futema
authors.forename: Katharina
authors.initials: K
authors.lastname: Pock
authors.forename: Sigurd
authors.initials: S
authors.lastname: Knaub
authors.forename: Olaf
authors.initials: O
authors.lastname: Walter
authors.forename: Laurenz
authors.initials: L
authors.lastname: Trawnicek
authors.forename: Jürgen
authors.initials: J
authors.lastname: Römisch
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood*; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D002648:Child; D004341:Drug Evaluation / Q000379:methods; D005164:Factor IX / Q000627:therapeutic use; D005169:Factor VIII / Q000276:immunology; D006467:Hemophilia A / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D012189:Retrospective Studies; D013917:Thrombin / Q000096:biosynthesis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000906:Antibodies; D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D005169:Factor VIII; D005164:Factor IX; D013917:Thrombin