TY - JOUR
T1 - Desmopressin response depends on the presence and type of genetic variants in patients with type 1 and type 2 von Willebrand disease
AU - Atiq, Ferdows
AU - Heijdra, Jessica
AU - Snijders, Fleur
AU - Boender, Johan
AU - Kempers, Eva
AU - van Heerde, Waander L.
AU - Maas, Dominique P.M.S.M.
AU - Krouwel, Sandy
AU - Schoormans, Selene C.
AU - de Meris, Joke
AU - Schols, Saskia E.M.
AU - van Galen, Karin P.M.
AU - van der Bom, Johanna G.
AU - Cnossen, Marjon H.
AU - Meijer, Karina
AU - Fijnvandraat, Karin
AU - Eikenboom, Jeroen
AU - Leebeek, Frank W.G.
N1 - 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.
PY - 2022/9/27
Y1 - 2022/9/27
N2 - 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 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.
AB - 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 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.
KW - Deamino Arginine Vasopressin/pharmacology
KW - Exons
KW - Humans
KW - von Willebrand Disease, Type 2/drug therapy
KW - von Willebrand Diseases/genetics
KW - von Willebrand Factor/genetics
UR - https://www.scopus.com/pages/publications/85138924898
U2 - 10.1182/bloodadvances.2021006757
DO - 10.1182/bloodadvances.2021006757
M3 - Article
C2 - 35446929
AN - SCOPUS:85138924898
SN - 2473-9529
VL - 6
SP - 5317
EP - 5326
JO - Blood Advances
JF - Blood Advances
IS - 18
ER -