Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct;22(10):2702-2712.
doi: 10.1016/j.jtha.2024.06.020. Epub 2024 Jul 9.

Type 2N von Willebrand disease: genotype drives different bleeding phenotypes and treatment needs

Mélanie Y Daniel  1 , Catherine Ternisien  2 , Sabine Castet  3 , Céline Falaise  4 , Roseline D'Oiron  5 , Fabienne Volot  6 , Nathalie Itzhar  7 , Brigitte Pan-Petesch  8 , Emmanuelle Jeanpierre  9 , Camille Paris  9 , Christophe Zawadzki  10 , Maximilien Desvages  10 , Annabelle Dupont  9 , Agnès Veyradier  7 , Yohann Repessé  11 , Antoine Babuty  2 , Marc Trossaërt  2 , Pierre Boisseau  12 , Cécile V Denis  13 , Peter J Lenting  13 , Jenny Goudemand  10 , Antoine Rauch  9 , Sophie Susen  14
Affiliations
Free article

Type 2N von Willebrand disease: genotype drives different bleeding phenotypes and treatment needs

Mélanie Y Daniel et al. J Thromb Haemost. 2024 Oct.
Free article

Abstract

Background: Type 2 Normandy von Willebrand disease (VWD2N) is usually perceived as a mild bleeding disorder that can be treated with desmopressin (DDAVP). However, VWD2N patients can be compound heterozygous or homozygous for different variants, with p.Arg854Gln (R854Q) being the most frequent causative one. There are limited data about the impact of 2N variants on VWD2N phenotype and DDAVP response.

Objectives: This study aims to describe the phenotype of VWD2N, including DDAVP response, according to genotype.

Methods: VWD2N patients with a complete genotype/phenotype characterization by the French reference center for VWD, including MCMDM-1VWD bleeding score, were eligible to be included in the study. Results of the DDAVP trial were also collected.

Results: A total of 123 VWD2N patients from the French registry were included in this study. Results were stratified according to the presence (R854QPos, n = 114) or absence (R854QNeg, n = 9) of at least 1 R854Q allele. Three R854QPos subgroups were further individualized: patients homozygous (R854QHmz, n = 55), compound heterozygous for R854Q and a null allele (R854Q/3, n = 48), or compound heterozygous for R854Q and another 2N variant (R854Q/2N, n = 11).

Fviii: C levels were significantly lower in R854QNeg and R854Q/3 patients compared with R854QHmz ones (P < .001 and P < .0001, respectively). R854QNeg patients were diagnosed earlier due to bleeding symptoms and had a higher bleeding score than R854QPos patients (P < .001). In DDAVP trial, FVIII:C survival was lower in VWD type 2N than in type 1 patients. R854QPos patients had a heterogeneous DDAVP response, which was best predicted by baseline FVIII:C level.

Conclusion: The heterogeneous genetic background of VWD2N drives different bleeding phenotypes and response patterns to DDAVP, underlining the clinical relevance of DDAVP trial to identify patients potentially eligible to alternative therapeutic options.

Keywords: desmopressin; factor VIII; genotype; type 2N von Willebrand disease; von Willebrand factor.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interests F.V. has received honoraria for consultancy, board, or oral presentations from CSL/Behring, LFB, Roche/Chugai, Takeda, Pfizer, and Sobi. Y.R. has received research support outside this work from Stago, Roche-Chugai, CSL Behring, and LFB and received Honoria for lectures or consultancy from Sobi, LFB, Octapharma, Roche-Chugai, CSL Behring, and Shire-Takeda. C.V.D. and P.J.L. are inventors on patents related to VWF. P.J.L. receives research support to institute from BioMarin, Sanofi, Sobi, and Roche. S.S. has received research support outside this work from CSL Behring, Roche-Chugai, Stago, and Siemens Healthineers and received honoraria for lectures or consultancy from BioMarin, Bioverativ, CSL Behring, Hemosonics, LFB, Novo Nordisk, Roche/Chugai, Sanofi, Siemens Healthineers, Shire-Takeda, and Sobi. The other authors have no competing interests to disclose.

MeSH terms

LinkOut - more resources