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肝衰竭患者人工肝治疗中不同抗凝剂的抗凝效果及安全性比较

Comparison of the anticoagulation effect and safety among different anticoagulants used in artificial liver therapy for patients with liver failure
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摘要 目的探讨枸橼酸钠与肝素钠抗凝对人工肝支持治疗肝衰竭患者抗凝效果及安全性的影响。方法选择2021年10月至2023年10月南阳市中心医院收治的101例行人工肝支持治疗的肝衰竭患者为研究对象,根据抗凝方法不同将患者分为枸橼酸钠组(n=41)和肝素钠组(n=60)。2组患者均给予保肝、抗病毒、维持电解质和酸碱平衡、合理膳食、卧床休息等维持内环境稳定的内科对症支持治疗,结合患者自身情况必要时输注人血白蛋白,同时通过人工肝支持系统给予人工肝支持治疗,枸橼酸钠组患者治疗过程中使用枸橼酸钠进行抗凝,肝素钠组患者治疗过程中使用肝素钠进行抗凝。于治疗前及治疗后24 h采集肘静脉血,检测凝血功能指标[血浆活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白原(FIB)]、肝功能指标[血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、直接胆红素(DBIL)、间接胆红素(IBIL)、白蛋白(ALB)]以及炎症指标[血浆C-反应蛋白(CRP)、白细胞介素-6(IL-6)、降钙素原(PCT)]水平,并检测单核细胞、中性粒细胞、血小板及淋巴细胞水平,计算单核细胞/淋巴细胞(MLR)、中性粒细胞/淋巴细胞(NLR)、血小板/淋巴细胞(PLR)比值及全身免疫炎症指数(SII);统计患者第1次人工肝治疗开始至随访结束时细菌性腹膜炎、肝肾综合征、消化道出血及肝性脑病发生情况;所有患者至少随访90 d,记录患者随访期间的生存状态、生存时间。结果2组患者治疗前血浆APTT、PT、TT、FIB水平比较差异无统计学意义(P>0.05)。2组患者治疗后24 h血浆APTT、PT、TT、FIB水平与治疗前比较均显著降低(P<0.05)。治疗后24 h,枸橼酸钠组患者血浆APTT、PT、TT水平显著低于肝素钠组(P<0.05),2组患者血浆FIB水平比较差异无统计学意义(P>0.05)。2组患者治疗前血清AST、ALT、DBIL、TBIL、IBIL及ALB水平比较差异无统计学意义(P>0.05)。2组患者治疗后24 h血清AST、ALT、DBIL、TBIL及IBIL水平与治疗前比较均显著降低(P<0.05);2组患者治疗后24 h血清ALB水平与治疗前比较差异无统计学意义(P>0.05)。治疗后24 h,2组患者血清AST、ALT、DBIL、TBIL、IBIL及ALB水平比较差异均无统计学意义(P>0.05)。2组患者治疗前CRP、IL-6、PCT、PLR水平及MLR、NLR、SII比较差异无统计学意义(P>0.05)。与治疗前比较,2组患者治疗后24 h CRP、IL-6、PCT、PLR水平及MLR、NLR显著降低,SII显著升高(P<0.05)。治疗后24 h,2组患者CRP、IL-6、PCT、PLR水平及MLR、NLR、SII比较差异无统计学意义(P>0.05)。枸橼酸钠组患者发生细菌性腹膜炎4例(9.76%),肝肾综合征3例(7.32%),消化道出血5例(12.20%),肝性脑病3例(7.32%),并发症发生率为36.59%(15/41);肝素钠组患者发生细菌性腹膜炎8例(13.33%),肝肾综合征6例(10.00%),消化道出血6例(10.00%),肝性脑病4例(6.67%),并发症发生率为40.00%(24/60);2组患者并发症发生率比较差异无统计学意义(χ^(2)=0.120,P>0.05)。枸橼酸钠组患者90 d生存率为68.3%(28/41),肝素钠组患者90 d生存率为66.7%(40/60),2组患者90 d生存率比较差异无统计学意义(χ^(2)=0.033,P>0.05)。结论肝衰竭患者行人工肝治疗使用枸橼酸钠与肝素钠均有一定疗效,且对生存率和术后并发症的影响相当,而枸橼酸钠更有利于改善患者的凝血功能。 Objective To investigate the anticoagulation effect and safety of sodium citrate and sodium heparin in artificial liver support therapy for patients with liver failure.Methods A total of 101 patients with liver failure who received artificial liver support therapy at Nanyang Central Hospital from October 2021 to October 2023 were selected as study subjects.According to different anticoagulation methods,the patients were divided into a sodium citrate group(n=41)and a heparin sodium group(n=60).Both groups of patients received symptomatic supportive medical treatment to keep internal environment stability,including liver protection,antiviral therapy,maintaining electrolyte and acid-base balance,a reasonable diet,and bed rest.Human serum albumin(ALB)was infused when necessary based on the patient's condition.At the same time,artificial liver support therapy was offered through the artificial liver support system.During the treatment process,the sodium citrate and heparin sodium groups adopted sodium citrate and heparin sodium for anticoagulation,respectively.Elbow venous blood was collected before treatment and 24 hours after treatment to measure coagulation function indicators[including activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),and fibrinogen(FIB)],liver function indicators[including serum alanine amino-transferase(ALT),aspartate amino-transferase(AST),total bilirubin(TBIL),direct bilirubin(DBIL),indirect bilirubin(IBIL),and ALB],and inflammatory indicators[including plasma C-reactive protein(CRP),interleukin-6(IL-6),and procalcitonin(PCT)].The levels of monocytes,neutrophils,platelets,and lymphocytes were also measured,and the monocyte-to-lymphocyte ratio(MLR),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and systemic immune-inflammation index(SII)were calculated.The occurrence of bacterial peritonitis,hepatorenal syndrome,gastrointestinal bleeding,and hepatic encephalopathy in the patients from the start of the first artificial liver treatment to the end of follow-up was recorded.Patients were followed up for at least 90 days,and their survival status and survival time during the follow-up period were recorded.Results There was no statistically significant difference in the levels of plasma APTT,PT,TT,and FIB between the two groups of patients before treatment(P>0.05).Compared with those before treatment,the levels of plasma APTT,PT,TT,and FIB in both groups were significantly reduced 24 hours after treatment(P<0.05).The plasma APTT,PT,and TT levels in the sodium citrate group were significantly lower than those in the heparin sodium group 24 hours after treatment(P<0.05),but there was no significant difference in plasma FIB levels between the two groups(P>0.05).There was no statistically significant difference in the levels of serum AST,ALT,DBIL,TBIL,IBIL,and ALB between the two groups before treatment(P>0.05).Compared with those before treatment,the levels of serum AST,ALT,DBIL,TBIL,and IBIL in both groups were reduced 24 hours after treatment(P<0.05).However,the difference in plasma ALB levels before treatment and 24 hours after treatment was not significant in both groups(P>0.05).There was no statistically significant difference in the levels of serum AST,ALT,DBIL,TBIL,IBIL,and ALB between the two groups 24 hours after treatment(P>0.05).There was no statistically significant difference in the levels of CRP,IL-6,PCT,PLR,MLR,NLR,and SII between the two groups before treatment(P>0.05).Compared with those before treatment,the levels of CRP,IL-6,PCT,PLR,MLR,and NLR were significantly reduced while the SII level was significantly increased in both groups 24 hours after treatment(P<0.05).There was no statistically significant difference in the levels of CRP,IL-6,PCT,PLR,MLR,NLR,and SII between the two groups 24 hours after treatment(P>0.05).In the sodium citrate group,there were 4 cases(9.76%)of bacterial peritonitis,3 cases(7.32%)of hepatorenal syndrome,5 cases(12.20%)of gastrointestinal bleeding,and 3 cases(7.32%)of hepatic encephalopathy,with a total postoperative complication rate of 36.59%(15/41).In the heparin sodium group,there were 8 cases(13.33%)of bacterial peritonitis,6 cases(10.00%)of hepatorenal syndrome,6 cases(10.00%)of gastrointestinal bleeding,and 4 cases(6.67%)of hepatic encephalopathy,with a total postoperative complication rate of 40.00%(24/60).There was no statistically significant difference in the total postoperative complication rate between the two groups(χ^(2)=0.120,P>0.05).The 90-day survival rate was 68.3%(28/41)in the sodium citrate group and 66.7%(40/60)in the heparin sodium group.There was no statistically significant difference in the 90-day survival rate between the two groups(χ^(2)=0.033,P>0.05).Conclusion For patients with liver failure undergoing artificial liver therapy,both sodium citrate and heparin sodium show certain therapeutic efficacy,with comparable impacts on survival rates and postoperative complications.However,sodium citrate outperforms heparin sodium in improving patients'coagulation function.
作者 王潇 王建刚 刘新宇 WANG Xiao;WANG Jiangang;LIU Xinyu(Department of Internal Medicine,Nanyang Central Hospital,Nanyang 473000,Henan Province,China;Department of Blood Purification,Nanyang Central Hospital,Nanyang 473000,Henan Province,China)
出处 《新乡医学院学报》 2025年第4期320-326,共7页 Journal of Xinxiang Medical University
基金 北京肝胆相照公益基金会资助课题(编号:RGGJJ-2021-021)。
关键词 肝衰竭 人工肝 肝素钠抗凝 枸橼酸钠抗凝 liver failure artificial liver heparin sodium anticoagulation sodium citrate anticoagulation
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