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
References
Apr 14, 1988·The New England Journal of Medicine·I M NilssonO Zettervall
Jun 16, 1995·The Journal of Biological Chemistry·J F HealeyP Lollar
Sep 1, 1994·Nucleic Acids Research·E G TuddenhamA Yoshioka
Apr 1, 1994·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·D DavidJ Lavinha
Feb 18, 1993·The New England Journal of Medicine·J M LusherR S Schwartz
Aug 30, 1996·The Journal of Biological Chemistry·J VoorbergM J Donath
Feb 26, 2000·British Journal of Haematology·J C RoelseJ Voorberg
Mar 8, 2000·Acta Haematologica·H SchrezenmeierA Raghavachar
Aug 5, 2000·Seminars in Thrombosis and Hemostasis·D H Scandella
Jun 9, 2001·The New England Journal of Medicine·P M Mannucci, E G Tuddenham
Citations
Jan 11, 2008·Blood·Adoración VencesláEduardo F Tizzano
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
Jun 25, 2008·Haemophilia : the Official Journal of the World Federation of Hemophilia·R d'OironM Jacquemin
Jul 13, 2006·Haemophilia : the Official Journal of the World Federation of Hemophilia·M FranchiniG Gandini
Aug 29, 2012·British Journal of Haematology·Donna M DiMichele
Dec 17, 2010·Blood·Ai-Hong ZhangDavid W Scott
Jan 24, 2006·Seminars in Hematology·Roseline d'OironUNKNOWN MHAI Study Group
Apr 24, 2013·Therapeutic Advances in Hematology·Char Witmer, Guy Young
Aug 1, 2007·Journal of Thrombosis and Haemostasis : JTH·D Dimichele
Jul 16, 2010·Haemophilia : the Official Journal of the World Federation of Hemophilia·K Peerlinck, M Jacquemin
Dec 10, 2009·Journal of Thrombosis and Haemostasis : JTH·M FranchiniG Lippi
Aug 4, 2011·Journal of Thrombosis and Haemostasis : JTH·D M Di Michele
Apr 8, 2014·Journal of Thrombosis and Haemostasis : JTH·M Y LimA D Ma
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