Phenotype analysis associated to p.Arg1315Cys (p.R1315C); the value of DDAVP and VWFpp/VWF:Ag ratio to reach the diagnosis.

WOODS AI; BLANCO AN; PAIVA J; SANCHEZ-LUCEROS A; KEMPFER AC; LAZZARI MA

Montpeliere

Congreso; Congress of ISTH-SSC; 2016

Abstract Preview This abstract is submitted!   Principio del formulario   Title: Phenotype analysis associated to p.Arg1315Cys (p.R1315C); the value of DDAVP and VWFpp/VWF:Ag ratio to reach the diagnosis Topic: von Willebrand disease SSC Subcommittee: von Willebrand Factor Author(s): A.I. Woods1, J. Paiva2, A.C. Kempfer1, A.N. Blanco3, A. Sanchez-Luceros1,3, M.A. Lazzari4 Institute(s): 1Imex-Conicet-Academia Nacional de Medicina, Laboratorio de Hemostasia y Trombosis, Buenos Aires, Argentina, 2Intitudo de Investigaciones Hematologicas, Academia Nacional de Medicina, Hemostasia y Trombosis, Buenos Aires, Argentina, 3Instituto de Investigaciones Hematologicas, Academia Nacional de Medicina, Hemostasia y Trombosis, Buenos Aires, Argentina, 4Imex-Conicet-Academia Nacional de Medicina, Buenos Aires, Argentina Travel Grant: I want to apply for Reach the World Disclosure: I have no potential conflict of interest. Text: Background: The p.R1315C has been described associated to 1C-VWD, 1-VWD, 2A-VWD, 2M-VWD, and 3-VWD phenotypes. Additional information can be derived from the DDAVP response and VWFpp/VWF:Ag (PP ratio). Aims: To show our experience in reaching the definitive diagnosis in 8 patients (pt) carrying heterozygous p.R1315C, with moderate-to-severe hemorrhagic events and a previous laboratory profile suggesting 2M-VWD. Methods: Studies before and after DDAVP infusion: FVIII:C (one-stage method) (nr 50-150 IU/dL), VWF:Ag (Ag) (nr 50-150 IU/dL) and VWFpp (PP) (ELISA), VWF:RCo (RCo) (nr 50-150 IU/dL) (aggregometric method). Bleeding score (BS) (ISTH), RCo/Ag (nr>0.6) and PP ratio (nr 0.9-2.14) were calculated. DDAVP response was tested in 6 pts and PP ratio in 8. Results: Pt 1 and 2: Ag and RCo did not reach normal levels (NL); RCo/Ag>0.6; high PP ratio. Pt 3: Ag and RCo reached NL; RCo/Ag>0.6; high PP ratio. Pt 4 and 5: high PP ratio. Diagnosis: 1C-VWD. Pt 6:Ag and RCo did not reach NL; RCo/Ag>0.6; normal PP ratio. Diagnosis: severe 1-VWD. Pt 7:Ag and RCo reached NL; RCo/Ag>0.6; normal PP ratio. Diagnosis: type 1-VWD. Pt 8:Ag did not reach NL; RCo did not change; RCo/Ag< 0.6; normal PP ratio. Initial 2M-VWD: confirmed. Conclusions: Both DDAVP response and PP ratio were useful to reach the diagnosis in our 8 pt. p.R1315C was associated to 1C-VWD in 5/8 pt (62.5%), severe type-VWD in 1 pt, type 1-VWD in 1 pt, 2M in 1 pt (12.5% each).  We found different phenotypes associated to p.R1315C, mainly 1C-VWD.  However, it should not be discarded the presence of other mutations in the VWF gene, which together with p.R1315C would result in the different phenotypes found in pt. Keywords: Mutation, Von Willebrand factor, Von Willebrand disease, Phenotype Preferred Presentation Method: Poster Only