Abstract Number: PB1585
Meeting: ISTH 2020 Congress
Theme: Platelet Disorders and von Willebrand Disease » VWF and von Willebrand Factor Disorders - Clinical Conditions
Background: VWD2N is a 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, 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 in a selected group of patients phenotypic and genotypically diagnosed.
Methods: We studied the F8 in five symptomatic patients with heterozygous DCV in VWF associated to VWD2N (Table 1). The severity of bleeding symptoms was evaluated by the ISTH/SSC bleeding assessment tool (ISTH/SSC BAT).
Patients were studied after signing the written-informed consent. The study was approved by local Ethics Committee.
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 (normal value [nv]>0.8) and VWF:RCo/VWF:Ag (nv>0.6) 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 sequenced (Sanger method). 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 (< 12 IU/dL) and FVIII/VWF:Ag< 0.11, abnormal BAT; 2 out of 3 patients had major bleeding episodes.
Patients with p.Arg854Gln had low FVIII levels (40-45 IU/dL) and FVIII/VWF:Ag< 0.7, and abnormal BAT. One patient had a major bleeding episode.
Conclusions: According to the FVIII levels and FVIII/VWF:Ag values of the patients, heterozygous p.Arg816Trp appears to cause a clearly dominant VWD2N.
Patients with p.Arg854Gln should be considered as VWD2N in spite of their heterozygous state in VWF given their bleeding tendency.
| Patient | Gender/age | DCV in VWF | DCV in F8 | FVIII | VWF:Ag | FVIII/VWF:Ag | BAT | Major bleeding |
| VJM | Female/63 | p.Arg816Trp | none | 12 | 110 | 0.11 | 15 | yes |
| BS | Male/4 | p.Arg816Trp | none | 8 | 73 | 0.11 | 6 | yes |
| BN | Female/2 | p.Arg816Trp | none | 4 | 76 | 0.05 | 2 | no |
| RC | Female/11 | p.Arg854Gln | none | 45 | 72 | 0.63 | 7 | yes |
| BMC | Female/16 | p.Arg854Gln | none | 40 | 82 | 0.49 | 3 | no |
[Table 1: Phenotypic and genotypic parameters in patients with VWD2N.]
To cite this abstract in AMA style:
Woods AI, Rossetti L, Paiva J, Romero ML, Blanco AN, Casinelli MM, De Brasi C, Sanchez-Luceros A. Type 2N von Willebrand Disease (VWD2N): Is it Always a Recessive Trait? [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/type-2n-von-willebrand-disease-vwd2n-is-it-always-a-recessive-trait/. Accessed October 1, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/type-2n-von-willebrand-disease-vwd2n-is-it-always-a-recessive-trait/