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Cross-reactivity to porcine factor VIII of factor VIII inhibitors in patients with haemophilia in Australia and New Zealand |
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| Authors: | J. V. Lloyd ,A. M. Street ,E. Berry &dagger ,J. McPherson ,H. Ekert ,A. Lammi ,W. R. McWhirter ,E. M. Duncan,E. L. Maxwell ,J. Rowell ,R. I. Baker ,M. F. Leahy ,D. Jupe |
| Affiliation: | Senior Haematologist, Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, SA.;Director, Haematology Unit, Alfred Hospital, Melbourne, Vic.;Consultant Haematologist, Department of Haematology, Auckland Hospital, NZ.;Senior Lecturer, Faculty of Medicine and Health Services, University of Newcastle/Mater Hospital, NSW.;Senior Consultant, Department of Clinical Haematology/ Oncology, Royal Children's Hospital, Melbourne, Vic.;Head, Department of Haematology, New Children's Hospital, Sydney, NSW.;Consultant Paediatrician, Department of Haematology, Royal Children's Hospital, Brisbane, Qld.;Senior Hospital Scientist, Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, SA.;Registrar, Department of Haematology, Aliked Hospital, Melbourne, Vic.;Director, Division of Haematology, Royal Brisbane Hospital, Brisbane, Qld.;Consultant Haematologist, Department of Haematology, Royal Perth Hospital, Perth, WA.;Head, Department of Haematology, Fremantle Hospital, Fremantle, WA.;Staff Haematologist, Department of Haematology, Royal Hobart Hospital, Hobart, Tas |
| Abstract: | Abstract Background: Inhibitory antibodies which neutralise factor VIII develop in 10–20% of individuals with inherited haemophilia A and rarely as autoantibodies in normal individuals to cause acquired haemophilia. The antibodies are directed against human factor VIII but cross-react to varying degrees with porcine factor VIII. Porcine factor VIII can be used for treatment in individuals with low cross-reactivity. Aims: To determine the cross-reactivity of factor VIII inhibitors between human factor VIII and porcine factor VIII, in a population of patients with inherited and acquired haemophilia A. Also, to determine whether patients with inherited haemophilia and inhibitors have a higher incidence of factor VIII gene inversion in intron 22. Methods: Samples and data sheets from 43 patients with inherited and ten with acquired haemophilia were submitted from hospitals in Australia and New Zealand. Inhibitor levels to human and porcine factor VIII were measured by the Bethesda method in 39 with inherited and nine with acquired haemophilia A. Results: Of 39 patients with inherited haemophilia A, cross-reactivity was 0% in 17 patients,1–19% in six, 20–39% in 11 and 40–80% in five. In six of nine patients with acquired haemophilia cross-reactivity was 7%. In inherited severe haemophilia A, the frequency of the intron 22 inversion was not greater in 37 study patients than in 28 patients without an inhibitor. Conclusions: Many patients in Australia and New Zealand with inhibitors to human factor VIII presently show a low or absent level of cross-reactivity to porcine factor VIII. These may respond to treatment with this concentrate at least in the short term. There remains a group of patients with high cross-reactivity who will respond only to recombinant factor Vila or prothrombin complex concentrates. |
| Keywords: | Haemophilia inherited haemophilia acquired haemophilia porcine factor VIII human factor VIII factor VIII inhibitors cross-reactivity |