摘要
目的探索多指标联合监测重症监护病房(ICU)患者低分子肝素(LMWH)的应用价值。方法回顾性病例对照研究。纳入2022年1月31至2023年11月30日在四川大学华西医院ICU接受LMWH治疗并监测抗Ⅹa活性的381例患者,其中男性264例,女性117例,年龄58(48,71)岁。收集临床资料和相关实验室检查结果,包括抗Ⅹa活性、抗凝血酶(AT)活性、凝血酶-抗凝血酶复合物(TAT)、纤溶酶-抗纤溶酶复合物(PIC)、常规凝血功能指标如活化部分凝血活酶时间(APTT)、以及常规肝肾功能损伤指标如丙氨酸转氨酶(ALT)和肌酐(CREA)等。根据患者血栓事件的发生发展情况将患者分为3组(血栓控制、血栓进展和出血组)。使用单因素及多因素Logistic回归分析影响抗Ⅹa活性的独立危险因素。结果共纳入381例患者,其中213例(55.9%)患者的血栓得到有效控制,81例(21.3%)患者血栓进展,87例(22.8%)患者发生出血事件。血栓控制组仅35例(16.4%)、血栓进展组仅16例(19.7%)、出血组仅16例(18.4%)患者的抗Ⅹa活性结果全部位于目标范围内(0.2~0.4 IU/ml)。3组患者间抗Ⅹa活性比较,差异无统计学意义(H=1.678,P=0.432)。单因素及多因素Logistic回归分析显示AT活性低是抗Ⅹa活性达标率低的独立危险因素(AT_(nadir),OR=1.031,95%CI 1.016~1.046,P<0.05)。与血栓进展组和出血组比较,血栓控制组用药期间TAT小于临界值的占比更高(H=8.519,P=0.014),TAT/PIC比值≤临界值的占比也更高(H=15.56,P<0.001)。与血栓控制或血栓进展组比较,发生出血事件患者的AT活性更低(H=14.968,P=0.001),APTT更长(H=6.815,P=0.033),ALT更高(H=13.774,P=0.001),CREA更高(H=14.068,P=0.001)。结论ICU患者的LMWH治疗需要进行实验室监测,抗Ⅹa活性虽能反映LMWH的抗凝效果,但不同结局患者之间抗Ⅹa活性无差异,因此抗Ⅹa活性用于评估LMWH治疗的ICU患者的血栓/出血风险的价值有限。TAT和TAT/PIC比值降低可提示血栓进展风险低,常规凝血指标以及常规肝肾功指标异常则更常见于发生出血事件的患者。
ObjectiveTo explore the clinical value of multi-parameter combined monitoring in guiding low-molecular-weight heparin(LMWH)therapy for intensive care unit(ICU)patients.MethodsA retrospective case-control study was conducted.A total of 381 patients who received LMWH therapy with anti-Ⅹa activity monitoring in the ICU of West China Hospital,Sichuan University between January 31st,2022,and November 30th,2023,were enrolled in this study.The cohort comprised 264 males and 117 females,with the age of 58(48,71)years old.Clinical data and relevant laboratory parameters were collected,including anti-Ⅹa activity,antithrombin activity(AT),thrombin-antithrombin complex(TAT),plasmin-antiplasmin complex(PIC),conventional coagulation parameters such as activated partial thromboplastin time(APTT),and indicators of hepatic/renal impairment such as alanine aminotransferase(ALT)and creatinine(CREA).Patients were stratified into three groups based on thrombotic event:thrombosis-controlled,progressive thrombosis,and bleeding group.Single-factor and adjusted multifactorial Logistic regression analysis were used to identify independent predictors of anti-xa activity levels.ResultsAmong 381 patients,thrombosis was controlled in 213(55.9%)patients,progressed in 81(21.3%)patients,and bleeding events occurred in 87(22.8%)patients.The patients whose anti-Ⅹa activity levels lay entirely within the target range(0.2-0.4 IU/ml):Only 35(16.4%)cases in the thrombosis-controlled group,16(19.7%)cases in the progressive thrombosis group,and 16(18.4%)in the bleeding group.No significant differences in anti-Ⅹa levels activity among the three groups(H=1.678,P=0.432).Both single-factor and adjusted multifactorial Logistic regression identified low AT activity as an independent risk factor for failure to achieve target anti-Ⅹa activity levels(AT nadir,OR=1.031,95%CI 1.016-1.046,P<0.05).Compared with the progressive thrombosis and bleedinggroup,the thrombosis-controlled group exhibited significantly higher proportion of TAT values below the cut-off value(H=8.519,P=0.014),and a higher proportion of TAT/PIC ratios below the cut-off(H=15.56,P<0.001).Patients with bleeding demonstrated significantly lower AT activity(H=14.968,P=0.001),prolonged APTT(H=6.815,P=0.033),higher ALT(H=13.774,P=0.001),and higher CREA(H=14.068,P=0.001)compared with the thrombosis-controlled or progressive thrombosis group.ConclusionLaboratory monitoring is required for low-molecular-weight heparin(LMWH)therapy in ICU patients.While anti-Ⅹa activity reflects the anticoagulant effect of LMWH,the utility of anti-Ⅹa activity for predicting thrombotic or hemorrhagic risks in LMWH treated ICU patients is limited.Reductions in TAT levels and TAT/PIC ratios are associated with a lower risk of thrombotic progression.Furthermore,abnormalities in conventional coagulation tests and standard hepatic/renal function parameters occur more frequently in patients experiencing hemorrhagic events.
作者
李勤
凌莉琴
李晓梅
刘超男
黄珣钡
王双
于志雨
周静
Li Qin;Ling Liqin;Li Xiaomei;Liu Chaonan;Huang Xunbei;Wang Shuang;Yu Zhiyu;Zhou Jing(Department of Laboratory Medicine,West China Hospital,Sichuan University,Chengdu 610041,China;Department of Blood Transfusion,Chengdu Second People′s Hospital of Chengdu,Sichuan 610045,China)
出处
《中华检验医学杂志》
北大核心
2025年第8期1008-1014,共7页
Chinese Journal of Laboratory Medicine
基金
国家自然科学基金(82302601)。
