摘要
目的对丝氨酸蛋白酶抑制剂(PAI-1)合并亚甲基四氢叶酸还原酶(MTHFR)基因突变导致的反复血栓形成患者及其家系资料进行分析, 提高临床对遗传性易栓症的诊疗水平。方法报道1例因咳嗽咳痰、发热伴左下肢疼痛入院的42岁女性患者, 先后接受标准剂量的低分子肝素以及利伐沙班方案治疗, 效果不佳, 通过多通道荧光定量分析仪, 采用微测序法(改良及原位杂交)检测 6 项易栓症基因, 查阅iGenKB 数据库得出患者及其近亲属的遗传风险值及风险区间。结果该患者诊断为PAI-1 4G/4G纯合突变合并MTHFR杂合突变导致的遗传性易栓症, 家族中多位近亲属存在PAI-1基因及MTHFR基因突变。在将抗凝治疗方案调整为利伐沙班, 并根据抗Ⅹa(利伐沙班)活性检测结果, 给予个体化剂量治疗后患者病情显著好转。结论 PAI-1 4G/4G纯合突变合并MTHFR杂合突变为罕见的遗传性易栓症突变基因, 对年轻患者进行基因筛查非常重要, 尤其是对于存在不明原因的血栓事件或规范抗凝治疗中仍有血栓复发的患者, 强调了给予利伐沙班个体化治疗方案的必要性。
Objective:To improve the clinical capacity for diagnosis and treatment of inherited thrombophilia through the analysis of the diagnostic and therapeutic process of recurrent thrombosis caused by combined PAI-1 and MTHFR gene mutations.Methods:We report a case of a 42-year-old female patient admitted with cough,expectoration,fever,and left lower limb pain.After suboptimal efficacy with standard-dose low-molecular-weight heparin(LMWH)and rivaroxaban,comprehensive thrombophilia genetic testing was performed.Six thrombophilia-associated genes were analyzed using a multi-channel fluorescent quantitative analyzer via the minisequencing method(modified in situ hybridization).The iGenKB database was queried to determine the patient′s and her close relatives′genetic risk scores and risk intervals.Results:The patient was diagnosed with hereditary thrombophilia caused by PAI-14G/4G homozygous mutation combined with MTHFR heterozygous mutation,with multiple close relatives in the family having mutations in the PAI-1 gene and MTHFR gene.Following adjustment of the anticoagulation regimen to rivaroxaban and implementation of individualized dosing guided by anti-Xa activity(rivaroxaban)monitoring,the patient′s condition improved significantly.Conclusions:The combination of a homozygous PAI-14G/4G mutation and a heterozygous MTHFR mutation represents a rare inherited thrombophilia genotype.Genetic screening in younger patients presenting with unexplained thrombotic events or experiencing recurrent thrombosis despite standardized anticoagulant therapy.Additionally,this case highlights the necessity for individualized rivaroxaban dosing regimens based on drug activity monitoring.
作者
余宏伟
张婧
胡艳秋
苏留超
王绪云
王剑雄
梅早仙
Yu Hongwei;Zhang Jing;Hu Yanqiu;Su Liuchao;Wang Xuyun;Wang Jianxiong;Mei Zaoxian(Department of Respiratory Medicine,Tianjin Hospital,Tianjin 300202,China;Graduate School of Clinical Sciences,Tianjin Medical University,Tianjin 300211,China)
出处
《中华结核和呼吸杂志》
北大核心
2025年第8期738-743,共6页
Chinese Journal of Tuberculosis and Respiratory Diseases
基金
天津市卫生健康委员会科技基金(TJWJ2022DZ008)。
