PO646-TUE Clinical and laboratory detection of transient neutralizing antibodies in severe von Willebrand disease on long term prophylaxis

SÁNCHEZ LUCEROS A; ALBERTO MF; KEMPFER AC; WOODS AI; BLANCO A; GROSSO SH; ROMERO ML; LAZZARI MA; BERMEJO EI; MESCHENGIESER SS

Toronto

Congreso; XXV Congress of the International Society on Thrombosis and Haemostasis and 61st Annual SSC Meeting.; 2015

International Society on Thrombosis and Haemostasis

Background: Patients with type 3 VWD and some severe type 2 andtype 1 VWD may benefit from long term prophylaxis (LTP) whenbleeding is frequent and severe. Neutralizing antibodies to VWF havebeen reported in 10?15% of VWD type 3 patients.Aims: To describe two cases on LTP that developed a transient neutralizingantibody associated to bleeding symptomsMethods: FVIII:C, VWF:Ag, VWF:RCo, and mixing studies as appropriate.IgG, IgM and IgA anti-VWF: by ELISA (purified VWF coated1 lg mL1, anti-Human IgG, IgM and IgA peroxidase labeled antibodies;cut-off < 100%).Results:Case A: 11 year-old boy, VWD type 3, on LTP (Haemate-P) due torecurrent hemarthrosis. In August 2014 he presented profuse epistaxisand gum bleeding for more than 7 days in spite of therapy. Laboratorytests showed: VWF:Ag 2% and VWF:RCo 2% without correctionon mixing studies and a high level of IgM anti-VWF (350%).Bleedings were treated on demand with higher dose of Haemate-P aswell as rFVIIa. After 2 months, symptoms disappeared, and VWFcorrected on mixing assays. The title of IgM anti-VWF declined(246%).Case B: 3 year-old girl, VWD type 2M (FVIII:C 35%, VWF:Ag 44%,VWF:RCo 7%, VWF:CB 11%, E1549K heterozygous mutation), onLTP with Haemate-P once a week due to recurrent severe epistaxis.After 2 months, she presented several nose bleeds, 24?28 hs after Haemate-P without local causes. Laboratory tests showed: VWF:Ag 6%and VWF:RCo 3% without correction on mixing studies. IgM anti-VWF was 233%. Bleeding episodes were treated on demand with Haemate-P. To date, she remains free of bleeding and laboratory parametersreturned to basal state.No symptoms of anaphylaxis associated to VWF concentrates wereobserved.Conclusion: We describe two severe VWD cases occurring in childrenon LTP. The role of free circulating antibodies to VWF is unclear, butthe regular testing for neutralizing antibodies should be done in thesepatients to manage the bleeding episodes. The appearance of inhibitorsis not restricted to VWD type 3.