Impact Factors And Predictive Biomarkers Associated With High Venous Thromboembolism Risk In Hospitalized Patients With Acute Exacerbation Of Chronic Obstructive Pulmonary Disease

ObjectiveThe aim of the study is to explore the impact factors and predictive biomarkers associated with high venous thromboembolism?VTE?risk in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease?AECOPD?,and to provide the theoretical proof for the early prevention of VTE with low molecular weight heparin?LMWH?based on the prethrombotic state?PTS?of the cohort.MethodsHospitalized patients with AECOPD were enrolled prospectively from April 2018to December 2018 whose medical information of gender,age,smoking history,chronic diseases,arterial blood gas and other clinical data were collected.These patients were assigned into the low-risk group and high-risk group by Padua risk assessment score?PRAS?.Then the high-risk hospitalized patients were divided into anticoagulation group and non-anticoagulation group according to whether LMWH was used.The plasma levels of new coagulation-fibrinolytic biomarkers such as thrombomodulin?TM?,thrombin-antithrombin complex?TAT?,plasminogen-?₂ plasminogen inhibitor complex?PIC?and tissue-type plasminogen activator-plasminogen activator inhibitor complex?t-PAI-C?as well as routine coagulation-fibrinolysis parameters were measured on admission?D₀?,the third day?D₃?and seventh day?D₇?after anticoagulate therapy in anticoagulation group or after admission in non-anticoagulation group and low-risk group.Same serum samples were also collected and measured in healthy individuals from the physical examination center as a control group.The levels of coagulative parameters and other clinical indices were measured and compared among the groups.The receiver operating characteristic?ROC?curves of these indices were generated,and the area under the curve?AUC?was calculated.The predictive values of the selected potential parameters were examined in binary regression analysis.Results?1?A total of 60 patients with AECOPD?18 cases in the low-risk group and 42cases in the high-risk group?and 20 normal controls were enrolled in our study.Non-invasiveventilationtreatment,deepveinpuncture/catheterization,bed rest/immobilized>3 days,pulmonary heart disease,type-II respiratory failure were more common in the high-risk group.The duration of hospitalization in the high-risk group was significantly longer than that in the low-risk group?P<0.05?.The levels of WBC,NEU,TM,TAT,PIC,t-PAI-C and PT,APTT,FIB,DD,P-FDP on admission in patients with AECOPD were higher while the levels of LYM,RBC,HCT,PLT,TT were lower than those in normal controls?P<0.05?.The levels of PaCO₂,WBC,NEU,TAT,and P-FDP were higher while the levels of PaO₂,LYM,and TT were lower in the AECOPD inpatients with high VTE risk than those with low VTE risk?P<0.05?.Correlation analysis showed that PaCO₂,WBC,NEU,TAT,P-FDP was positively correlated with PRAS,while PaO₂,LYM,TT was negatively correlated with PRAS.Levels of PaCO₂?OR=1.183,95%CI:1.056,1.325?,NEU?OR=1.447,95%CI:1.035,2.022?,and TT?OR=0.319,95%CI:0.139,0.731?were independently associated with higher risk of VTE.The AUC of TAT,TT and FDP were 0.751,0.697and 0.665 respectively.Combination of three indicators demonstrated largest AUC?0.837?with the sensitivity of 81.0%and specificity of 77.8%respectively.?2?There were 40 patients with AECOPD whose subgroup with 9 cases in the low-risk group,21 cases in the non-anticoagulation group and 10 cases in the anticoagulation group.The levels of TAT,PIC,FIB in the patients of three groups all had the trend to decrease.The levels of TAT,PIC and FIB in the patients of anticoagulation group were lower on D₇ than those before anticoagulation treatment and the level of FIB in the patients of anticoagulation group was lower than that on D₃?P<0.05?,but there was no significant change in the low-risk group and non-anticoagulation group?P>0.05?.There were no differences in the levels of TM,t-PAI-C,DD,P-FDP among patients in the three groups?P>0.05?.The level of APTT in the patients of anticoagulation group had a tendency to increase but no significance?P>0.05?.ConclusionThe hospitalized patients with AECOPD show a hypercoagulable state.Non-invasiveventilator-assistedventilation,deepvenipuncture/catheterization,bed/immobilized time>3 days,duration of hospitalization,chronic pulmonary heart disease,and type-II respiratory failure are considered to be associated with higher risk of VTE.The levels of PaCO₂,NEU,and TT may be independent predictors of the high risk of in-hospital VTE in AECOPD patients,and serve as predictors for PTS in the early stage of VTE.On the basis of routine treatment combined with LMWH prophylaxis in patients with AECOPD suffering with a high risk of VTE,the coagulation-fibrinolysis indexes can be partially improved,which may reduce the risk of VTE in the patients with AECOPD in hospital.