Desmopressin response depends on the presence and type of genetic variants in patients with type 1 and type 2 von Willebrand disease
Atiq, Ferdows; Heijdra, Jessica; Snijders, Fleur; Boender, Johan; Kempers, Eva; van Heerde, Waander L.; Maas, Dominique P.M.S.M.; Krouwel, Sandy; Schoormans, Selene C.; de Meris, Joke; Schols, Saskia E.M.; van Galen, Karin P.M.; van der Bom, Johanna G.; Cnossen, Marjon H.; Meijer, Karina; Fijnvandraat, Karin; Eikenboom, Jeroen; Leebeek, Frank W.G.
(2022) Blood Advances, volume 6, issue 18, pp. 5317 - 5326
(Article)
Abstract
Patients with type 1 and type 2 vonWillebrand 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
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is not yet fully understood. Our primary aimwas 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 fromtheWillebrand 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 andMultiplex 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.
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Keywords: Deamino Arginine Vasopressin/pharmacology, Exons, Humans, von Willebrand Disease, Type 2/drug therapy, von Willebrand Diseases/genetics, von Willebrand Factor/genetics, Hematology, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 2473-9529
Publisher: The American Society of Hematology
Note: Funding Information: This study was supported by research funding from the Dutch Hemophilia Foundation (Stichting Haemophilia), Shire (Takeda), and CSL Behring (unrestricted grant). Funding Information: Conflict-of-interest disclosure: F.A. received the CSL Behring Professor Heimburger Award 2018 and a travel grant from Sobi. J.H. received the CSL Behring Professor Heimburger Award 2018. J.B. started working at Sobi after finishing this research project. W.L.v.H. reports speaker, consultant, and travel fees from Takeda, Bayer, CSL Behring, and Sobi. He is also cofounder and CSO of Enzyre. M.H.C. has received investigator-initiated research and travel grants over the Publisher Copyright: © 2022 by The American Society of Hematology.
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