Department of Hematology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Pediatric Hematology, Erasmus Medical Center Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Blood Adv. 2022 Sep 27;6(18):5317-5326. doi: 10.1182/bloodadvances.2021006757.
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.
1 型和 2 型血管性血友病（VWD）患者可使用去氨加压素进行治疗。尽管先前的研究表明，导致 VWF 基因变异的位置与 1 型 VWD 患者对去氨加压素的反应有关，但 VWF 基因变异与去氨加压素反应之间的关系尚未完全阐明。我们的主要目的是比较 1 型 VWD 患者中有无 VWF 基因变异者对去氨加压素的反应。其次，我们研究了 1 型和 2 型 VWD 患者中去氨加压素反应是否取决于特定的 VWF 基因变异。我们纳入了荷兰 Willebrand 研究中的 250 例患者：72 例 1 型无 VWF 基因变异者，108 例 1 型有变异者，45 例 2A 型，16 例 2M 型和 9 例 2N 型患者。使用离子半导体测序和多重连接依赖性探针扩增分析 VWF 基因。所有无变异的 1 型 VWD 患者均出现完全对去氨加压素的反应，64.3%的有变异的 1 型患者和 31.3%的 2 型患者出现完全对去氨加压素的反应（P＜0.001）。尽管去氨加压素反应存在个体间的巨大差异，但具有相同变异的患者具有相似的去氨加压素反应。例如，在 6 例存在外显子 4 至 5 缺失的 1 型患者中，去氨加压素后 1 小时 VWF 活性为 0.81 IU/mL，变异系数为 22.9%。总之，所有无 VWF 基因变异的 1 型 VWD 患者对去氨加压素均有反应。在 1 型和 2 型 VWD 患者中，VWF 变异者对去氨加压素的反应高度依赖于 VWF 基因变异。
