IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Type 2N von Willebrand disease: Is it always a recessive trait?
Autor/es:
ROSSETTI LC; BLANCO AN; SÁNCHEZ-LUCEROS A;; PAIVA J; CASINELLI MM; WOODS AI;; ROMERO ML; DE BRASI CD
Lugar:
Milan
Reunión:
Congreso; Congreso Internacional; 2020
Institución organizadora:
ISTH
Resumen:
Type 2N von Willebrand disease (VWD2N): is it always a recessive trait?Woods AI1, Rossetti L2, Paiva J3, Romero ML3, Casinelli MM3, De Brasi C2, Blanco AN3, Sánchez-Luceros A1-31Laboratorio de Hemostasia y Trombosis, IMEX-CONICET-Academia Nacional de Medicina. Ciudad Autónoma de Buenos Aires, Argentina2Laboratorio de Genética de la Hemofilia, IMEX-CONICET-Academia Nacional de Medicina. Ciudad Autónoma de Buenos Aires, Argentina3Departamento de Hemostasia y Trombosis, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina. Ciudad Autónoma de Buenos Aires, Argentina VWD2N is a relatively rare form of VWD, described as a recessive disease due to disease-causing variant (DCV) in homozygous or double/compound-heterozygous state. Heterozygotes individuals are considered carriers of the defect, and mostly asymptomatic; those homozygotes, and double/compound-heterozygotes have clinical manifestations and laboratory phenotype frequently mistaken for those of mild hemophilia A.Aims: To show the variable inheritance of VWD2N according to the DCV and gender in a selected group of patients phenotypic and genotypically diagnosed.Methods:We studied F8 gene in six patients with heterozygous DCV in VWF associated to VWD2N phenotype (Table 1). The severity of each bleeding symptom was evaluated by the ISTH/SSC bleeding assessment tool (ISTH/SSC BAT).Laboratory tests: FVIII:C (one-stage method), VWF:Ag (ELISA),VWF:RCo (aggregometry). Mixing studies of the patient/control plasmas to evaluate the presence of inhibitors were undertaken by APTT and VWF:RCo. FVIII:C/VWF:Ag and VWF:RCo/VWF:Ag were calculated in each patient. Genomic DNA was extracted from peripheral blood. Exons 17-27 of the VWF and all 26 exons of F8 were PCR-amplified and directly Sanger-sequenced. F8 exons were previously heteroduplex-analysed by conformation sensitive gel electrophoresis.Results:Both normal VWF:Ag and VWF:RCo levels, and normal VWF:RCo/VWF:Ag were observed in all patients. No DCV were observed in F8 (Table 1).Patients with p.Arg816Trp had very low FVIII (