Desmopressin response depends on the presence and type of genetic variants in patients with type 1 and type 2 von Willebrand disease
Ferdows Atiq, Jessica M. Heijdra, Fleur Snijders, Johan Boender, Eva K 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
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.