PMID: 11918545Mar 29, 2002Paper

Factor VIII inhibitor in a patient with mild haemophilia A and an Asn618-->Ser mutation responsive to immune tolerance induction and cyclophosphamide

British Journal of Haematology
André J VlotEveline P Mauser-Bunschoten

Abstract

We describe a patient with mild haemophilia A (original value of factor VIII activity 0.30 U/ml) who developed an inhibitor (36.1 Bethesda U/ml) which cross-reacted with his endogenous factor VIII. This caused a decline in basal factor VIII level (< 0.01 U/ml) and severe haemorrhagic events. Treatment to induce immune tolerance was started with factor VIII/von Willebrand factor (VWF) concentrates, but inhibitor levels increased progressively and the patient suffered serious bleeding. Cyclophosphamide was administered and, after 8 months treatment, factor VIII levels increased to 0.20 U/ml and the inhibitor could no longer be detected. Screening of his factor VIII gene revealed a missense mutation in exon 13 that predicts substitution of Asn618-->Ser in the A2 domain of factor VIII. Immunoprecipitation analysis showed that the antibodies present in the patient's plasma reacted with metabolically labelled A2 domain and, to a lesser extent, with factor VIII light chain. Inhibitory antibodies were completely neutralized by recombinant A2 domain, whereas no neutralization was observed after the addition of factor VIII light chain (A3-C1-C2) and C2 domain. More detailed analysis showed that the majority of inhibitory antibodies were ...Continue Reading

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Citations

Apr 17, 2004·Haemophilia : the Official Journal of the World Federation of Hemophilia·F W G LeebeekK S G Jie
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·A SharathkumarM D Carcao
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Jun 25, 2014·European Journal of Haematology. Supplementum·Britta Antonia Petra Laros-van GorkomJan Astermark
Apr 26, 2014·The Cochrane Database of Systematic Reviews·Abha H AthaleAlfonso Iorio
Jul 1, 2020·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Zahra Rezaieyazdi, Hassan Mansouritorghabeh
Jan 24, 2007·Anesthesiology Clinics·Doreen E Soliman, Lynn M Broadman

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