【作者】 李雪；

【导师】 陈志营；

【作者基本信息】 吉林大学 ， 临床医学硕士（专业学位）， 2024， 硕士

【摘要】 背景:当慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease,COPD）患者发生急性加重或合并心力衰竭、呼吸衰竭时,常常表现为咳嗽、呼吸困难加重、双下肢水肿,临床上很容易将这种表现归因于疾病本身的加重,而忽视了深静脉血栓形成（Deep Venous Thrombosis,DVT）,甚至肺栓塞（Pulmonary Embolism,PE）的可能,以至于错过最佳的治疗时间,甚至失去最佳抢救机会。Stein根据美国国家出院调查的数据进行回顾性研究发现,在25年中,5839.2万例患者被诊断为COPD,其中63.2万例COPD患者合并DVT,38.1万例合并PE,DVT、PE的诊断率仅为1.08%、0.65%^[1]。另外一项前瞻性研究对所有入院的AECOPD患者均行血栓筛查,PE患病率为25.0%^[2]。由此可见目前临床工作中对于COPD患者发生静脉血栓栓塞症的认识不足。慢性阻塞性肺疾病和静脉血栓栓塞症（Venous Thrombus Embolism,VTE）是严重影响人们健康的两种常见病和多发病,尽管随着医学水平的不断提高,特别是彩色多普勒超声、CT肺动脉造影（CT Pulmonary Angiography,CTPA）以及放射性核素肺通气/血流灌注显像的推广,越来越多的患者得到及时诊治,预后有所改善,但对于COPD合并静脉血栓的早期筛查,临床上仍存在很大的困难。目的:分析慢性阻塞性肺疾病患者发生下肢静脉血栓的影响因素,帮助我们判断COPD患者血栓潜在风险,及早预防、识别和治疗血栓。同时选择合适的血栓风险评估模型,帮助临床医务人员方便、快捷的筛选出血栓患者,以提高患者生存质量,降低患者住院时间、住院费用以及病死率。方法:1.收集2020.1-2022.11入住吉林大学白求恩第三医院呼吸内科,临床诊断为慢性阻塞性肺疾病并行双下肢静脉彩超检查的患者,共272名。收集患者的一般资料、合并症、实验室检查结果、动脉血气分析等。2.根据双下肢静脉彩超检查有无静脉血栓,将其分为血栓组和对照组,其中血栓组68例,对照组204例。3.用Excel软件完成数据的收集与记录,确认数据无误后采用SPSS 25.0进行统计分析。结果:1.单因素分析,血栓组患者的年龄、住院时间、女性患者比例、合并呼吸衰竭、合并肺源性心脏病的比例大于对照组,差异具有统计学意义（P<0.05）。血栓组的NLR、PCT、BNP、PT、D-D、TG大于对照组,Pa O₂、EOS、ALB小于对照组,差异具有统计学意义（P<0.05）。血栓组Padua、Caprini、Wells-DVT评分均高于对照组,差异具有统计学意义（P<0.05）。两组患者在BMI、吸烟饮酒史、肿瘤病史、高血压病、糖尿病、房颤、p H、Pa CO₂、WBC、RBC、Hb、PLT、Mb、APTT、FIB、TC、HDL-C、LDL-C方面无统计学差异（P>0.05）。2.相关分析发现Padua、Wells-DVT、Caprini评分与D-二聚体呈正相关（P<0.05）,Padua、Caprini评分与Pa O₂呈负相关（P<0.05）。D-二聚体和Caprini关联性更大（r=0.518,P<0.05）,Pa O₂和Padua关联性更大（r=-0.267,P<0.05）。3.二元Logistic回归分析发现年龄越大（OR=1.127,95%CI 1.074-1.182,P<0.001）,住院时间越长（OR=1.096,95%CI 1.003-1.198,P=0.042）,D-二聚体越高（OR=2.021,95%CI 1.290-3.168,P=0.002）,甘油三酯越高（OR=2.062,95%CI 1.192-3.565,P=0.010）发生下肢静脉血栓的可能性越大,是COPD患者发生下肢静脉血栓的独立危险因素。4.绘制受试者工作特征曲线,单个因素预测能力最大的是D-二聚体,AUC0.852,约登指数最大为0.574,对应的临界值为0.54mg/L,诊断COPD患者发生下肢静脉血栓的灵敏度为85.3%,特异度72.1%。D-二聚体与其他三项指标联合预测,预测能力均大于单个危险因素,其中D二聚体联合年龄预测COPD发生下肢静脉血栓的AUC最大,为0.844（95%CI 0.793-0.895,P<0.001）,灵敏度为70.6%,特异度为85.3%。将四项指标联合,AUC为0.850（95%CI 0.798-0.901,P<0.001）,灵敏度为86.8%,特异度为68.6%。5.三项血栓风险评估模型中Padua风险评估模型的AUC最大,为0.977,约登指数最大为0.867,对应的临界值为4.5分,灵敏度和特异度最高,分别为94.1%、92.6%。结论:1.女性COPD患者、合并肺源性心脏病、呼吸衰竭,更容易发生下肢静脉血栓。2.中性粒-淋巴细胞比率、降钙素原、B型脑钠肽越高,凝血酶原时间越长,Pa O₂、嗜酸细胞数、白蛋白越低,慢阻肺患者发生下肢静脉血栓可能性越大,对预测静脉血栓的发生有一定的指导价值。3.慢阻肺患者年龄越大,住院时间越长,D-二聚体、甘油三酯越高,发生静脉血栓栓塞的危险性越大,是COPD患者发生下肢静脉血栓的独立危险因素。4.Padua、Wells-DVT、Caprini三项风险评估模型均可预测COPD患者下肢静脉血栓的发生,Padua风险评估模型诊断价值最大,灵敏度、特异度最高。5.三项血栓风险评估模型危险因素中均未纳入D-二聚体、Pa O₂,但其与三项血栓风险评估模型均有相关关系,D-二聚体是静脉血栓发生的独立危险因素,且呼吸科住院患者具有低氧血症的特点,可以考虑将D-二聚体、Pa O₂纳入其中,优化评分系统,提高COPD患者静脉血栓筛查成功率。更多还原

【Abstract】 Background:For Chronic Obstructive Pulmonary Disease（COPD）patients undergoing acute deteriorations or encountering secondary conditions like heart failure and respiratory failure,clinical presentations such as coughing,worsened breathlessness,and edema in both lower limbs are prevalent.These symptoms are routinely considered to be indicative of the exacerbation of the underlying COPD,thus overshadowing the likelihood of Deep Venous Thrombosis（DVT）or Pulmonary Embolism（PE）,leading to missed golden opportunities for timely treatment and potentially life-saving interventions.Based on a retrospective study by Stein,which examined data from the National Hospital Discharge Survey in the United States over a span of 25 years,out of58.392 million COPD patients,632,000 were found to have DVT and 381,000 had PE,with the diagnosis rates for DVT and PE being as low as 1.08%and 0.65%,respectively^[1].Another forward-looking study that screened all hospital-admitted AECOPD patients for thrombosis discovered a PE prevalence of 25.0%^[2].These findings underscore the clinical oversight in detecting venous thromboembolism（VTE）among COPD sufferers.Despite advancements in medical technologies such as color Doppler ultrasound,CT Pulmonary Angiography（CTPA）,and nuclear medicine lung ventilation/perfusion scans,the challenge of early thrombosis screening in COPD cases persists.Objective:Analysis of the factors affecting the occurrence of lower extremity venous thrombosis in patients with chronic obstructive pulmonary disease helps us to judge the potential risk of thrombosis,and prevent,identify and treat thrombosis as early as possible.At the same time,the appropriate risk assessment model was selected to help clinical staff to screen thrombus patients conveniently and quickly,so as to improve the quality of life of patients and reduce the length of hospital stay,hospital cost and fatality rate of patients.Methods:1.A total of 272 patients admitted to the Respiratory Department of The Third Bethune hospital of Jilin University from January 2020 to November 2022,clinically diagnosed with chronic obstructive pulmonary disease and accompanied by venous color ultrasound examination of both lower limbs were collected.General data,comorbidities,laboratory test results and arterial blood gas analysis were collected.2.The patients were divided into thrombus group and control group according to venous ultrasonography of both lower limbs,of which 68 cases were thrombus group and 204 cases were control group.3.Use Excel to complete data collection and record,and use SPSS 25.0 for statistical analysis after confirming that the data is correct.Results:1.Univariate analysis showed that the age,length of hospital stay,proportion of female patients,combined respiratory failure,and combined pulmonary heart disease,in the thrombus group were higher than those in the control group,with statistical significance（P<0.05）.NLR,PCT,BNP,PT,D-D and TG in the thrombus group were higher than those in the control group,while Pa O₂,EOS and ALB were lower than those in the control group,with statistical significance（P<0.05）.The scores of Padua,Caprini and Wells-DVT in thrombus group were higher than those in control group,and the differences were statistically significant（P<0.05）.There were no significant differences between the two groups in BMI,smoking and drinking history,tumor history,hypertension,diabetes,atrial fibrillation,p H,Pa CO₂,WBC,RBC,Hb,PLT,Mb,APTT,FIB,TC,HDL-C,and LDL-C（P>0.05）.2.Correlation analysis found that Padua,Wells-DVT and Caprini scores were positively correlated with D-dimer（P<0.05）,while Padua and Caprini scores were negatively correlated with Pa O₂（P<0.05）.D-dimer is more correlated with Caprini（r=0.518,P<0.05）,Pa O₂ is more correlated with Padua（r=-0.267,P<0.05）.3.Binary Logistic regression analysis found that the older of age（OR=1.127,95%CI 1.074-1.182,P<0.001）,the longer of hospital stay（OR=1.096,95%CI 1.003-1.198,P=0.042）,the higher of D-dimer（OR=2.021,95%CI 1.290-3.168,P=0.002）,the higher of triglyceride（OR=2.062,95%CI 1.192-3.565,P=0.010）,the higher of lower extremity venous thrombosis,which is an independent risk factor for lower extremity venous thrombosis in COPD patients.4.According to the Receiver Operating Characteristic Curve of subjects,the largest predictive ability of a single factor was D-dimer,AUC 0.852,and the highest Jorden index was 0.574,corresponding to a critical value of 0.54mg/L.The sensitivity and specificity of diagnosing lower extremity venous thrombosis in COPD patients were85.3%and 72.1%.The prediction ability of D-dimer combined with other three indexes was greater than that of a single risk factor.Among them,the AUC of D-dimer combined with age predicted the occurrence of lower extremity venous thrombosis in COPD was the largest,0.844（95%CI0.793-0.895,P<0.001）,the sensitivity was 70.6%,and the specificity was 85.3%.The AUC of the four indexes was 0.850（95%CI 0.798-0.901,P<0.001）,the sensitivity was 86.8%,and the specificity was 68.6%.5.Among the three thrombus risk assessment models,the Padua risk assessment model had the highest AUC was 0.977 and the highest Jorden index was 0.867,corresponding to a critical value of 4.5 points,the highest sensitivity and specificity were 94.1%and 92.6%.Conclusion:1.Female patients with COPD,pulmonary heart disease and respiratory failure are more likely to develop lower extremity venous thrombosis.2.The higher the NLR,PCT,BNP,the longer the PT,the lower the Pa O₂,EOS and ALB,the greater the likelihood of lower extremity venous thrombosis in COPD patients,which has certain guiding value for predicting the occurrence of venous thrombosis.3.The older the COPD patients,the longer the hospital stay,the higher the D-dimer and triglyceride,and the greater risk of venous thromboembolism,which is an independent risk factor for lower extremity venous thrombosis in COPD patients.4.Padua,Wells-DVT and Caprini can all predict the occurrence of lower extremity venous thrombosis in COPD patients,and Padua has the highest diagnostic value,sensitivity and specificity.5.D-dimer and Pa O₂ were not included in the risk factors of the three thrombosis risk assessment models,but they were related to the three thrombosis risk assessment models.D-dimer is an independent risk factor for the occurrence of venous thrombosis,and inpatients in the respiratory department have the characteristics of hypoxemia.D-dimer and Pa O₂ can be considered to optimize the scoring system and improve the screening rate of lower extremity venous thrombosis in COPD patients.更多还原