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

Blood Advances - Tập 6 - Trang 5317-5326 - 2022
Ferdows Atiq1, Jessica Heijdra2, Fleur Snijders1, Johan Boender1, Eva Kempers1, Waander L. van Heerde3,4, Dominique P.M.S.M. Maas3, Sandy Krouwel3, Selene C. Schoormans3, Joke de Meris5, Saskia E.M. Schols3, Karin P.M. van Galen6, Johanna G. van der Bom7,8, Marjon H. Cnossen2, Karina Meijer9, Karin Fijnvandraat10,11, Jeroen Eikenboom12,13, Frank W.G. Leebeek1
1Department of Hematology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands
2Department of Pediatric Hematology, Erasmus Medical Center Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
3Department of Hematology, Radboud University Medical Center, Hemophilia Treatment Center Nijmegen-Eindhoven-Maastricht, Nijmegen, The Netherlands
4Enzyre, Novio Tech Campus, Nijmegen, The Netherlands
5Netherlands Hemophilia Society, Leiden, The Netherlands
6Department van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
7Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
8Jon J van Rood Center for Clinical Transfusion Medicine, Sanquin Research, Leiden, the Netherlands
9Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
10Department of Pediatric Hematology, Amsterdam University Medical Center, University of Amsterdam, Emma Children's Hospital, Amsterdam, The Netherlands
11Sanquin Research, Department of Molecular Cellular Hemostasis, Amsterdam, The Netherlands
12Division of Thrombosis and Hemostasis, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
13Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands

Tóm tắt

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.

Tài liệu tham khảo

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Blood Advances

Tập 6

5317-5326

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