title: Continuous infusion of porcine factor VIII in patients with haemophilia A and high-responding inhibitors: stability and clinical experience.
abstract: A multicentre retrospective survey was conducted to assess the efficacy and side-effect profile of porcine factor VIII (pFVIII:C) given by continuous infusion (CI) to patients with congenital haemophilia A and inhibitors. Twenty-nine episodes in 18 patients were treated by CI of pFVIII:C. Efficacy was graded as good in 79% of infusions and fair in 17%. There was a failed response in only one episode. Fourteen percent of patients experienced transfusion reactions with bolus doses, but no reactions were observed in patients given CI. There were no severe reactions. All the reactions resolved following interruption of the infusion and administration of steroids. Premedication did not prevent reactions. In this series the median decrease in platelet count after bolus injection of pFVIII:C was -67 X 10(9) L(-1) compared with a median decrease of -2 x 109 L(-1) during the course of CI, thus, continuous infusion of pFVIII:C appears to have less effect on platelet count than bolus injection. An anamnestic response was associated with 77% of infusions. This high rate of anamnesis reflects patient selection, in that they were all known to have high-level high-responding FVIII inhibitors with cross-reactivity to pFVIII. After reconstitution, the pFVIII:C showed little loss in factor VIII activity in solution over a 24-h period. We conclude that pFVIII:C may be effectively administered by CI to patients with haemophilia A and high-responding FVIII inhibitors. CI is the probably the mode of administration of choice for intensive replacement therapy with pFVIII.
authors.affiliation: University Department of of Haematology, Manchester Royal Infirmary, Manchester, UK.
authors.forename: P
authors.initials: P
authors.lastname: O'Gorman
authors.forename: D M
authors.initials: DM
authors.lastname: Dimichele
authors.forename: C K
authors.initials: CK
authors.lastname: Kasper
authors.forename: P M
authors.initials: PM
authors.lastname: Mannucci
authors.forename: E
authors.initials: E
authors.lastname: Santagostini
authors.forename: C R
authors.initials: CR
authors.lastname: Hay
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004341:Drug Evaluation; D005169:Factor VIII / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy*; D006470:Hemorrhage / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D007223:Infant; D007263:Infusions, Parenteral / Q000592:standards*; D007518:Isoantibodies / Q000097:blood*; D010976:Platelet Count; D012189:Retrospective Studies; D013552:Swine; D016896:Treatment Outcome
chemical_list: D007518:Isoantibodies; D005169:Factor VIII