因子 IX p.A37V 突变导致苯丙香豆素治疗患者严重出血。
Factor IX p.A37V mutation causes severe bleeding in a patient with phenprocoumon therapy.
机构信息
Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
Clinic for Internal Medicine (Tumor Research), University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
出版信息
Eur J Med Res. 2021 Jun 29;26(1):63. doi: 10.1186/s40001-021-00533-7.
BACKGROUND
Bleeding is the most common complication of oral anticoagulants, due to inadequate dosing.
CASE PRESENTATION
This report describes the clinical course of a patient who developed severe bleeding under therapy with phenprocoumon, despite an INR in the lower therapeutic range. Strikingly, aPTT was prolonged, while factor IX activity was significantly reduced. Acquired hemophilia was excluded, due to missing detection of inhibitors. Finally, sequencing part of the factor IX gene including nucleotide position c.110 revealed a hemizygous factor IX mutation c.110C > T p (Ala37Val).
CONCLUSIONS
In rare cases, missense mutations in factor IX propeptide are associated with severe bleeding complications. The substitution of alanin at position 37 to either valin or threonin (Ala37Val or Ala37Thr) leads to hypersensitivity to vitamin k antagonists.
背景
出血是口服抗凝剂最常见的并发症，这是由于剂量不足导致的。
病例介绍
本报告描述了一位患者的临床病程，该患者在接受苯丙香豆素治疗时出现严重出血，尽管 INR 处于较低的治疗范围内。显著的是，APTT 延长，而因子 IX 活性显著降低。由于未检测到抑制剂，故排除获得性血友病。最后，对包括核苷酸位置 c.110 在内的因子 IX 基因的一部分进行测序显示杂合子因子 IX 突变 c.110C > T p (Ala37Val)。
结论
在罕见情况下，因子 IX 前肽中的错义突变与严重出血并发症相关。位置 37 的丙氨酸替换为缬氨酸或苏氨酸（Ala37Val 或 Ala37Thr）会导致对维生素 K 拮抗剂的敏感性增加。
Zotero 插件