Desmopressin response depends on the presence and type of genetic variants in patients with type 1 and type 2 von Willebrand disease.

Abstract

Patients with type 1 and type 2 von Willebrand disease (VWD) can be treated with desmopressin. Although a previous study has shown that the location of the causative VWF gene variant is associated with desmopressin response in type 1 VWD, the association between variants in the VWF gene and desmopressin response is not yet fully understood. Our primary aim was to compare desmopressin response in type 1 VWD patients with and without a VWF gene variant. Secondly, we investigated whether desmopressin response depends on specific VWF gene variants in type 1 and type 2 VWD. We included 250 patients from the Willebrand in the Netherlands study: 72 type 1 without a VWF gene variant, 108 type 1 with a variant, 45 type 2A, 16 type 2M, and 9 type 2N patients. VWF gene was analyzed with ion semiconductor sequencing and Multiplex Ligation-dependent Probe Amplification. Complete response to desmopressin was observed in all type 1 VWD patients without a variant, 64.3% of type 1 patients with a variant, and 31.3% of type 2 patients (P < .001). Despite a large interindividual variability in desmopressin response, patients with the same variant had comparable desmopressin responses. For instance, in 6 type 1 patients with exon 4 to 5 deletion, mean VWF activity at 1 hour after desmopressin was 0.81 IU/mL, with a coefficient of variation of 22.9%. In conclusion, all type 1 VWD patients without a VWF gene variant respond to desmopressin. In type 1 and type 2 VWD patients with a VWF variant, desmopressin response highly depends on the VWF gene variants.

• Authors: Ferdows Atiq, Jessica Heijdra, Fleur Snijders, Johan Boender, Eva Kempers, Waander L van Heerde, Dominique P M S M Maas, Sandy Krouwel, Selene C Schoormans, Joke de Meris, Saskia E M Schols, Karin P M van Galen, Johanna G van der Bom, Marjon H Cnossen, Karina Meijer, Karin Fijnvandraat, Jeroen Eikenboom, Frank W G Leebeek
• Journal: Blood advances (Blood Adv) Vol. 6 Issue 18 Pg. 5317-5326 (09 27 2022) ISSN: 2473-9537 [Electronic] United States
• PMID: 35446929 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Chemical References

• von Willebrand Factor
• Deamino Arginine Vasopressin

Topics

• Deamino Arginine Vasopressin (pharmacology, therapeutic use)
• Exons
• Humans
• von Willebrand Disease, Type 2 (drug therapy, genetics)
• von Willebrand Diseases (genetics)
• von Willebrand Factor (genetics)