服用华法林国际标准化比值升高患者的出血风险预测因素分析

Predictors of bleeding risk in patients with high international normalized ratio (INR) values in warfar in therapy

目的探讨服用华法林导致国际标准化比值(INR)升高患者出血不良事件的危险因素。方法纳入2013年8月至2019年8月就诊于北京同仁医院使用华法林抗凝治疗INR升高(INR>3.5)的患者资料。根据住院期间是否发生出血,分为非出血组和出血组。记录患者基线资料、实验室检查以及联合用药情况。结果共纳入201例患者,非出血组126例,出血组75例;大出血12例,轻微出血63例。出血组和非出血组的年龄、性别、吸烟史、饮酒史、既往出血史及首次应用华法林的比例,合并高血压、糖尿病、冠心病、外周动脉粥样硬化、血脂异常、脑卒中、心功能不全的比例比较,差异无统计学意义(均P>0.05)。非出血组合并肝功能异常比例[7.14%(9/126)]、肾功能不全的比例[11.90%(15/126)]、贫血比例[4.76%(6/126)]、合并低蛋白血症比例[4.76%(6/126)]及感染性疾病比例[20.63%(26/126)]均低于出血组[16.00%(12/75)、32.00%(24/75)、29.33%(22/75)、16.00%(12/75)、44.00%(33/75);χ^2值分别为3.942、12.140、23.675、7.283、12.377,均P<0.05]。共筛选出对华法林有影响的药物54种,合并应用最多的是心血管系统药物(162例,占80.60%)、血液系统药物(155例,占77.11%)、抗感染药物(112例,占55.72%)、消化系统药物(82例,占40.80%)、内分泌系统药物(56例,占27.86%)。轻微出血组和大出血组的INR最高值[4.58(3.94,5.90)、4.96(4.03,8.27)]、HAS-BLED评分[3.00(2.00,3.00)、3.00(2.25,3.00)分]高于非出血组[4.00(3.74,4.35)、2.00(1.00,3.00)分,均P<0.01],而轻微出血组及大出血组比较差异无统计学意义(P>0.05)。结论导致服用华法林患者INR升高因素较多,如肝肾功能异常、贫血、低蛋白血症、应用抗菌药物等,对患者合并用药需谨慎。

Objective To investigate the risk factors of bleeding events in patients with high international normalized ratio(INR)values(INR>3.5)in warfarin therapy.Methods Two hundred and one patients with high INR values(INR>3.5)during warfarin therapy admitted in Beijing Tongren Hospital from August 2013 to August 2019 were enrolled.The bleeding occurred in 75 patients(bleeding group)and did not occur in 126 cases(non-bleeding group)during hospitalization.The bleeding group included 12 major bleeding patients and 63 minor bleeding patients.The baseline information,laboratory results and medication of other drugs were recorded.Results There were no significant differences in age,sex,smoking history,drinking history,previous bleeding history and the proportion of first application of warfarin between the two groups(P>0.05).The proportion of patients with liver dysfunction[7.14%(9/126)],renal dysfunction[11.90%(15/126)],anemia[4.76%(6/126)],hypoproteinemia[4.76%(6/126)],infectious diseases[20.63%(26/126)]in non-bleeding group were significantly lower than that in bleeding group[16.00%(12/75),32.00%(24/75),29.33%(22/75),16.00%(12/75),44.00%(33/75);χ^2=3.942,12.140,23.675,7.283,12.377,respectively;all P<0.05].A total of 54 kinds of drugs were associated with the INR elevation.The most commonly used drugs were cardiovascular system drugs(n=162,80.60%),blood system drugs(n=155,77.11%),anti-infective drugs(n=112,55.72%),digestive system drugs(n=82,40.80%),and endocrine system drugs(n=56,27.86%).The INR values[4.58(3.94,5.90),4.96(4.03,8.27)]and the HAS-BLED scores[3.00(2.00,3.00),3.00(2.25,3.00)]in minor bleeding group(n=63)and major bleeding group(n=12)were higher than those in non-bleeding group[4.00(3.74,4.35),2.00(1.00,3.00),P<0.01),but there was no significant difference in INR values and HAS-BLED scores between minor bleeding group and major bleeding group(P>0.05).Conclusion There are many factors leading to the increase of INR in patients taking warfarin,such as abnormal liver and kidney function,anemia,hypoproteinemia,and the use of antibacterial drugs.It is necessary to be cautious about co-administration in these patients.