Pharmacokinetics, coagulation factor consumption and clinical efficacy in patients being switched from full-length FVIII treatment to B-domain-deleted r-FVIII and back to full-length FVIII. 2009

C Rea, and A Dunkerley, and B Sørensen, and S Rangarajan
Haemostasis Research Unit, Centre for Haemophilia and Thrombosis, Guy's and St Thomas NHS Foundation Trust, London, UK.

Concerns have been raised regarding pharmacokinetic performance, efficacy and safety of B-domain-deleted recombinant FVIII (BDD rFVIII). The objective of this study was to perform a retrospective survey of half-life measurements, efficacy and safety in patients with severe haemophilia A, switching treatment from full-length factor VIII (FL FVIII) to BDD rFVIII and then back to FL FVIII. We hypothesized that half-life of FVIII would be equal regardless of product and that total factor consumption and bleeding frequency would be indistinguishable. We report on inhibitor development and outcome following surgery. Patients with severe haemophilia A, exposed to BDD rFVIII were identified from a database. A retrospective analysis of laboratory data and medical notes was undertaken. No significant difference was detected between the half-life measurements during the switch from FL FVIII (T/2 median 9.15 h, range 6.4-22) to BDD rFVIII (T/2 median 9.7, range 4.7-16.8) and back to FL FVIII (T/2 median 9.0, range 5.0-19.5). There was no significant difference in coagulation factor usage (BDD rFVIII median 4803 IU kg(-1) year(-1), range 659-11 304; FL FVIII median 5349, range 1691-10 146), nor bleeds. Eleven received BDD rFVIII to cover surgical procedures, with no reports of excess bleeding. Thirty-three patients received significant exposure to BDD rFVIII and one developed a low titre inhibitor. BDD rFVIII was found to be equivalent to other FVIII products in terms of pharmacokinetics, clinical efficacy and safety in this study group.

UI MeSH Term Description Entries
D008297 Male Males
D001779 Blood Coagulation Factors Endogenous substances, usually proteins, that are involved in the blood coagulation process. Clotting Factor,Coagulation Factors,Blood Coagulation Factor,Clotting Factors,Coagulation Factor,Coagulation Factor, Blood,Coagulation Factors, Blood,Factor, Coagulation,Factors, Coagulation,Factor, Blood Coagulation,Factor, Clotting,Factors, Blood Coagulation,Factors, Clotting
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D005169 Factor VIII Factor VIII of blood coagulation. Antihemophilic factor that is part of the factor VIII/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin. Coagulation Factor VIII,Factor VIII Clotting Antigen,Factor VIII Coagulant Antigen,Factor VIII Procoagulant Activity,Thromboplastinogen,Blood Coagulation Factor VIII,F VIII-C,Factor 8,Factor 8 C,Factor Eight,Factor VIIIC,Hyate-C,Hyatt-C,F VIII C,Hyate C,HyateC,Hyatt C,HyattC
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006467 Hemophilia A The classic hemophilia resulting from a deficiency of factor VIII. It is an inherited disorder of blood coagulation characterized by a permanent tendency to hemorrhage. Factor VIII Deficiency,Hemophilia,Autosomal Hemophilia A,Classic Hemophilia,Deficiency, Factor VIII,Factor 8 Deficiency, Congenital,Factor VIII Deficiency, Congenital,Haemophilia,Hemophilia A, Congenital,Hemophilia, Classic,As, Autosomal Hemophilia,Autosomal Hemophilia As,Classic Hemophilias,Congenital Hemophilia A,Congenital Hemophilia As,Hemophilia A, Autosomal,Hemophilia As,Hemophilia As, Autosomal,Hemophilia As, Congenital,Hemophilias, Classic
D006470 Hemorrhage Bleeding or escape of blood from a vessel. Bleeding,Hemorrhages
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000293 Adolescent A person 13 to 18 years of age. Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths

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