Department of Hematology, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands.
Thromb Haemost. 2013 Mar;109(3):440-9. doi: 10.1160/TH12-06-0383. Epub 2013 Jan 24.
Desmopressin causes two- to six-fold increase of factor VIII (FVIII) in mild or moderate haemophilia A patients. However, responses are variable and little is known whether this is associated with F8 gene mutation. The study objective was to assess the relationship between F8 gene mutation and desmopressin response in haemophilia A patients. Desmopressin response (absolute and relative) was determined in 97 hemophilia A patients. Four amino acid changes (Arg2169His, Pro149Arg, Asn637Ser, and Arg612Cys) and a number of other mutations leading to an aberrant FVIII protein or FVIII deficiency were analysed. Patients with Arg2169His showed significantly lower FVIII levels before and after desmopressin compared to all other mutations (p<0.001). Pro149Arg amino acid change showed significantly lower FVIII levels 1 hour after desmopressin compared to all other mutations (p<0.005). An absolute response with FVIII≥0.50 IU/ml after 1 hour was observed in 41% (9 of 22) of patients with Arg2169His; however, this was not sustainable after 6 hours in any of these subjects. No patients with Pro149Arg mutation (n=6) showed an absolute response with FVIII≥0.50 I U/ml. Patients with other mutations showed significantly more complete and partial responses. Relative responses did not differ between mutations. Our study shows that haemophilia A patients with amino acid change Arg2169His or Pro149Arg have a decreased desmopressin response with regard to FVIII levels as compared to other mutations. Our results indicate that response to desmopressin is dependent on the F8 gene mutation type, despite the fact that multiple factors influence the desmopressin response, even within families.
去氨加压素可使轻度或中度血友病 A 患者的因子 VIII（FVIII）增加 2 至 6 倍。然而，反应各不相同，并且对于这种反应是否与 F8 基因突变有关知之甚少。本研究旨在评估血友病 A 患者的 F8 基因突变与去氨加压素反应之间的关系。在 97 名血友病 A 患者中测定了去氨加压素的反应（绝对值和相对值）。分析了四个氨基酸变化（Arg2169His、Pro149Arg、Asn637Ser 和 Arg612Cys）和导致异常 FVIII 蛋白或 FVIII 缺乏的其他一些突变。与所有其他突变相比，Arg2169His 患者的去氨加压素治疗前后 FVIII 水平明显降低（p<0.001）。与所有其他突变相比，Pro149Arg 氨基酸变化在去氨加压素后 1 小时 FVIII 水平明显降低（p<0.005）。Arg2169His 的患者在 1 小时后 FVIII≥0.50 IU/ml 的绝对反应率为 41%（22 例中的 9 例）；然而，在这些患者中，任何患者在 6 小时后均无可持续的绝对反应。没有 Pro149Arg 突变（n=6）的患者表现出 FVIII≥0.50 IU/ml 的绝对反应。具有其他突变的患者显示出明显更多的完全和部分反应。突变之间的相对反应没有差异。我们的研究表明，与其他突变相比，具有氨基酸变化 Arg2169His 或 Pro149Arg 的血友病 A 患者的去氨加压素反应在 FVIII 水平上降低。我们的结果表明，尽管有多种因素影响去氨加压素反应，甚至在家族内，去氨加压素反应仍取决于 F8 基因突变类型。
