Identification of a novel polymorphism in p.N258 of the GP1BA gene.

SANCHEZ LUCEROS A; ALBERTO F; KEMPFER AC; WOODS AI; BLANCO A; GROSSO S; ROMERO L; LAZZARI MA; BERMEJO E; MESCHENGIESER SS.

Toronto (Ontario)

Congreso; XXV ISTH Congress; 2015

Background: Patients with type 3 VWD and some severe type 2 and type 1 VWD may benefit from long term prophylaxis(LTP) when bleeding is frequent and severe. Neutralizing antibodies to VWF have been reported in 10% ? 15% of VWDtype 3 patients.Aims: To describe two cases on LTP that developed a transient neutralizing antibody associated to bleeding symptomsMethods: FVIII:C, VWF:Ag, VWF:RCo, and mixing studies as appropriate. IgG, IgM and IgA anti-VWF: by ELISA (purifiedVWF coated 1μg/mL, 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 to recurrent hemarthrosis. In August 2014 hepresented profuse epistaxis and gum bleeding for more than 7 days in spite of therapy. Laboratory tests showed:VWF:Ag 2% and VWF:RCo 2% without correction on mixing studies and a high level of IgM anti-VWF (350%). Bleedingswere treated on demand with higher dose of Haemate-P as well as rFVIIa. After 2 months, symptoms disappeared, andVWF corrected 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 heterozygousmutation), on LTP with Haemate-P once a week due to recurrent severe epistaxis. After 2 months, she presented severalnose 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 parameters returned to basal state.No symptoms of anaphylaxis associated to VWF concentrates were observed.Conclusion: We describe two severe VWD cases occurring in children on LTP. The role of free circulating antibodies toVWF is unclear, but the regular testing for neutralizing antibodies should be done in these patients to manage thebleeding episodes. The appearance of inhibitors is not restricted to VWD type 3.Disclosure of Interest: None DeclaredKeywords: Bleeding, Inhibitor, Therapy, Von Willebrand disease