甲磺酸萘莫司他在高出血风险患者连续性肾脏替代治疗中的应用

The application of nafamostat mesylate in continuous renal replacement therapy for patients with a high risk of bleeding

摘要:

目的 探讨甲磺酸萘莫司他（NM）在高出血风险患者连续性肾脏替代治疗（CRRT）中应用的有效性和安全性。方法 回顾性分析2024年2月—2025年1月在南京医科大学附属淮安第一医院接受CRRT的高出血风险的111例患者的透析资料。根据不同抗凝方式分为NM组、枸橼酸盐组和无肝素组，分别有41、34、36例。主要观察指标为CRRT时长、滤器及管路凝血情况。次要观察指标为CRRT前后的血红蛋白、血小板、凝血指标［凝血酶原时间（PT）、国际标准化比值（INR）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、纤维蛋白原（FIB）、D-二聚体］情况，比较各组资料的差异性。结果 各组患者年龄、体质量指数、性别构成、血管通路类型构成、高出血风险原因构成、白蛋白、甘油三酯、空腹血糖、血红蛋白、血小板、PT、INR、APTT和TT比较，差异均无统计学意义（P >0.05）。无肝素组FIB水平高于枸橼酸盐组，NM组D-二聚体水平高于无肝素组（P <0.05）。各组患者CRRT时长、CRRT滤器凝血分级、CRRT总体凝血比较，差异均有统计学意义（P <0.05），各组患者CRRT抗凝、CRRT管路凝血比较，差异均无统计学意义（P >0.05）。各组患者滤器使用数量比较，差异有统计学意义（P <0.05）。NM组和枸橼酸盐组患者CRRT前后血红蛋白、血小板计数、PT、INR、APTT、TT、FIB、D-二聚体比较，差异均无统计学意义（P >0.05）；无肝素组患者CRRT前后血红蛋白、血小板计数、INR、APTT、TT、FIB比较，差异均无统计学意义（P >0.05），无肝素组CRRT后PT较CRRT前下降，D-二聚体较CRRT前升高（P <0.05）。各组患者CRRT前血红蛋白、血小板计数、PT、INR、APTT、TT比较，差异均无统计学意义（P >0.05），各组患者CRRT前FIB、D-二聚体比较，差异均有统计学意义（P <0.05）。各组患者CRRT后血红蛋白、血小板计数、INR、APTT、TT、D-二聚体比较，差异均无统计学意义（P >0.05）。各组患者CRRT后PT、FIB比较，差异均有统计学意义（P <0.05）。结论 NM在高出血风险患者的CRRT治疗中可发挥良好的抗凝作用，且安全性好，不会增加出血风险。

Abstract:

Objective To explore the efficacy and safety of nafamostat mesylate (NM) in continuous renal replacement therapy (CRRT) for patients at high risks of bleeding.Methods A retrospective analysis was conducted on the dialysis data of 111 patients at a high risk of bleeding who underwent CRRT at The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University between February 2024 and January 2025. According to the anticoagulation strategy used, patients were divided into the NM group (n = 41), citrate anticoagulation group (n = 34), and no-heparin group (n = 36). The primary outcomes were CRRT duration and filter/circuit clotting events. Secondary outcomes included changes in hemoglobin, platelet count, and coagulation parameters before and after CRRT, including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), thrombin time (TT), and levels of fibrinogen (FIB) and D-dimer. The differences among the groups were compared.Results There were no significant differences among the three groups in age, body mass index (BMI), sex distribution, vascular access type, causes of bleeding risks, albumin, triglycerides, fasting blood glucose, hemoglobin, platelet count, PT, INR, APTT, or TT (all P > 0.05). The no-heparin group had significantly higher fibrinogen levels than the citrate group, whereas the NM group had significantly higher D-dimer levels than the no-heparin group (both P < 0.05). CRRT duration, filter clotting grade, and overall clotting incidence differed significantly among the three groups (all P < 0.05). However, no significant differences were found in anticoagulation efficacy or circuit clotting rates (all P > 0.05). The number of filters used differed significantly among the three groups according to Fisher’s exact test (P < 0.05). In the NM group, comparisons of hemoglobin, platelet count, PT, INR, APTT, TT, and levels of FIB and D-dimer before and after CRRT using the Z test showed no statistically significant differences (all P > 0.05). Similarly, in the citrate group, no significant differences were observed in hemoglobin, platelet count, PT, INR, APTT, TT, or levels of FIB and D-dimer before and after CRRT (all P > 0.05). In the no-heparin group, no significant differences were found in hemoglobin, platelet count, INR, APTT, TT, or FIB levels before and after CRRT (all P > 0.05), while PT was significantly lower after CRRT than before CRRT (P < 0.05), and D-dimer levels were significantly increased after CRRT compared with pre-CRRT levels (P < 0.05). Before CRRT, there were no significant differences among the three groups in hemoglobin, platelet count, PT, INR, APTT, TT, or levels of FIB and D-dimer (all P > 0.05). After CRRT, hemoglobin, platelet count, INR, APTT, TT, and D-dimer levels remained comparable among the three groups, with no statistically significant differences (all P > 0.05). However, significant differences were observed among the three groups in post-CRRT PT and FIB levels (both P < 0.05).Conclusion NM provides effective anticoagulation during CRRT in patients at high risk of bleeding and demonstrates a favorable safety profile without increasing the risk of bleeding.