Venous Thromboembolism In Inflammatory Bowel Disease:A Multicenter Study Into Incidence And Risk Factors,and Association Between Coagulation Function And Disease Activity

Part1 Incidence and risk factors of venous thromboembolism in inflammatory bowel disease:a nation-wide multicenter retrospective studyBackground and aim:Inflammatory bowel disease(IBD)is characterized by chronic inflammation of the gastrointestinal tract,which primarily consists of Crohn's disease(CD)and ulcerative colitis(UC).Apart from the gastrointestinal related symptoms,IBD patients are sometimes presented with extra-intestinal manifestations and comorbidities such as arthrisits,arteritis and venous thromboembolism(VTE).Multiple studies from the western population showed that patients with IBD have higher risk of VTE,which greatly compromised the quality of life and IBD prognosis.In the past decade,incidence of IBD in China has been rising,and the quality of care for IBD patients has been improving.However,the incidence and risk factors for VTE among Chinese IBD patients are not known,and therefore there is a lack of concern for thromboprophylaxis in clinical practice.Therefore,this multi-center retrospective study is performed,aiming to investigate the incidence and risk factors of VTE among Chinese IBD patients,and to provide evidence for improving the quality of care for Chinese IBD patients.Method:A total of 17 hospitals in China participated in this retrospective investigation.IBD patients treated at these hospitals between 2011.1.1 to 2016.6.30 were consecutively enrolled.Demographical and clinical information(IBD subtype,date of IBD diagnose,duration of IBD-related symptoms,history of bowel resection),date of the first and the last clinical visit,VTE events,use of VTE screening and prophylaxis were recorded from medical file review.For patients with VTE,specific diagnostic and treatment course were recorded.Incidence density was used as the indicator for the incidence of VTE;demographical and clinical features of VTE events,VTE screening and prophylaxis were analyzed.For inpatients with VTE,a case control analysis was performed.IBD related factors(disease subtypes,disease activity,medication),and VTE related risk factors(surgery,pregnancy,and comorbidities)were compared between patients with and without VTE;independent risk factors for VTE among IBD inpatients were investigated using Logistic regression.Results:Based on the 8459 IBD patients enrolled from the 17 hospitals,incidence rate of VTE was 37.18/10000 person-years,with 0.54%of all IBD patients affected.Incidence of deep venous thrombosis of the lower extremities(DVT)was highest(21.63/10000 person-years),and incidence of pulmonary embolism(PE)and intra-abdominal venous thrombosis were 5.66 and 6.47/10000 person-years,respectively.VTE significantly prolonged hospital stay among elder IBD patients,and demonstrated poor prognosis with one patient died(2.2%).20.31%and 1.94%of the patients received VTE screening and thromboprophylaxis,respectively.VTE incidence did not differ between different IBD subtypes and genders,but increased with advanced age.The incremental of incidence with age was more pronounced among CD patients and female gender.The proportion of bowel resection was higher among patients with VTE.Inpatients with VTE were mostly having active disease and 25%were having direct risk factors for VTE including surgery,history of tumor,and venous line insertions.About 30%of patients were having comorbidities that predisposed them to higher VTE risks.Multivariant Logistic regression discovered that for UC patients,severe disease flares and immobilization were independent risk factors for VTE,whereas past use of 5-aminosalicylic acids was protective against VTE.For CD patients,severe disease flare and past use of glucocorticoids were independent risk factors for VTE.Conclusions:This is the first multi-center study from Chinese IBD patients,which included over 8000 patients,and discovered that the incidence rate of VTE was similar with some reports from the western population.VTE screening and prophylaxis were low and not standardized.For inpatients with IBD,severe disease flares was the independent risk factors for VTE.This study suggests that clinicians should be ware of VTE among IBD patients as a serious,yet not uncommon complication,and that prophylactic measures need to be taken for patients with risk factors such as severe disease flares.Part 2 Associations between coagulation function and disease activity in inflammatory bowel diseaseBackground and aim:Risk of venous thromboembolism(VTE)rises among patients with inflammatory bowel disease(IBD).Inflammation affects coagulation process through several mechanisms including damaging the endothelial cells,leading to hypercoagulablestate and consequently higher VTE risks.Studies dicovered that coagulation abnormalities existed in IBD patients and correlated with degree of inflammation,but these studies didn't further analyze the coagulation function between different IBD subgroups.Treatment of IBD focuses on inflammation control and symptom relief;biologics such as anti tumor necrosis factor a monoclonal antibody shows good effects with control of intestinal inflammation and therefore has become an important pharmacological therapy for IBD in China.However,there's lack of data from large patient group analyzing how platelet and coagulation function changes as the result of inflammation control with biologics.Therefore,to further understand the how inflammatory status interacts with hypercoagulable state in IBD,the second part of the thesis was designed.The current study adopted commonly used coagulation tests and inflammatory markers for IBD,aiming to analyze the coagulation function of IBD patients with different disease subtypes,their correlation with disease activity,and also to explore changes in platelet and coagulation function after use of biologies.Method:This is a retrospective,single center study.IBD inpatients,including Crohn's disease(CD)and ulcerative colitis(UC),who were treated at one hospital between 2014.8.1 to 2017.8.1 were consecutively recruited.Demographical and IBD related clinical information(IBD subtypes and disease activity),coagulation function,erythrocyte sediment rate(ESR),C reactive protein(CRP)were recorded.People coming to hospital for regular health exam were enrolled as control and their coagulation function tests were recorded.For CD patients on biologics,all the tests above were recorded before the first and the sixth infusions.Test results were compared between different IBD subtypes,before and after use of biologics,and correlation analysis with disease activity was performed.Results:1)Platelet and coagulation function of IBD patients were significantly different compared to healthy controls,regardless of disease activity.Fibrinogen(FG)and D dimers(DDI)were abnormally elevated.Degrees of these differences correlated with ESR,CRP and disease activity assessment.FG most stronly correlated with disease activity.2)UC and CD patients were different regarding the aspects of coagulation function.DDI was higher among UC patients and more correlated with inflammation as opposed to CD patietns,whereas most other coagulation function among CD patients were more prominently deviated from the norm compared to UC patients.3)Prothrombin time was significantly prolonged in UC patients with pancolitis;FG was higher among CD patients with inflammatory type and perianal disease;these differences coincided with differences in inflammatory markers between these groups,therefore different coagulation function among patients with different disease characteristics may be due to differences in inflammation.4)After the use of biologics,platelet test and coagulation tests were normalized among CD patients,and these changes correlated with changes in inflammation.Conclusions:This study proved that there are associations between coagulation function and inflammatory status among IBD patients;fibrinogen and platelet most strongly correlated with active disease,and thus could be two potential indicators for degrees of inflammation among IBD patients.Inspite of the association between coagulation function and disease activity,UC and CD presented with different characteristics in coagulation abnormalities.In addition,extensive colitis in UC,inflammatory type and perianal disease in CD were more prominent in coagulation abnormalities,which could be due to different inflammatory conditions among these groups.Lastly,this study discovered that after the use of biologics,coagulation abnormalities were alleviated,which suggested that inflammation control is crucial to the maintainance of normal coagulation function in IBD patients.