Clinical Study On Thrombosis In Patients With Primary Immune Thrombocytopenia

Background and ObjectivePrimary immune thrombocytopenia(ITP)is a common clinical hemorrhagic disease.Now the main therapeutic approaches aim at reducing the destruction and accelerating the production of platelet,in order to increase the platelet count,which could prevent or alleviate the bleeding symptoms.However,in our clinical practice,it was observed that arterial or venous thrombosis occurred in some ITP patients during or after the treatment period,and PLT count was usually lower than normal range at the time of thrombopoiesis.The occurrence of thrombosis not only adds the pain of patients and prolongs the length of stay(LOS)of inpatients,but also increases the degree of difficulty for us to choose the follow-up therapeutic schedule,which can find us caught in a dilemma to get a balance between anticoagulant therapy to inhibit thrombogenesis and platelet increasing therapy to prevent the risk of bleeding.Recently,some foreign studies acclaimed the incidence of thrombosis in ITP patients was higher than it in common population.But few studies reported in our nation.Therefore,we undertook a retrospective investigation in a large cohort of ITP patients with a total of 669 cases,enrolled from Qilu Hospital,Shandong University,to analyze the incidence of thrombosis and investigate the risk factors of developing thrombosis in patients with ITP,so as to strengthen early detection for ITP patients accompanied by the thrombosis tendency,monitor and adjust the therapeutic schedule and target in time,and effectively reduce morbidity and mortality for these patients.MethodsWe collected all adult ITP patients treated from Department of Hematology of Qilu Hospital during the period from 2007.1.1 to 2016.7.30.A total of 669 cases were included in this research,with deletion of patients missing in 41 cases and untreated in 48 cases.Among these,there were males in 252 cases,females in 417 cases,with a median age of 40 years old.The numbers for diagnostic classification were 166(new-diagnosed ITP),191(persistent ITP),312(chronic ITP).Diagnostic criteria were based on Consensus of Chinese experts on diagnosis and treatment of adult primary immune thrombocytopenia(version 2016).All enrolled patients received at least one ITP-specific therapy during follow-up period.The personal information of enrolled patients was checked up by case management computer system of Qilu Hospital.Through telephone follow-up survey,researchers recorded all thrombotic events meeting the outcome definitions,as well as the personal and laboratory data at diagnosis.ITP-specific treatments received at any time from diagnosis to the time of last follow-up or to the time of first thrombotic episode were registered.According to whether occurred thrombotic events or not,all patients were divided into two groups:thrombus group,and non-thrombus group.Univariate analyses of quantitative variables and frequencies were calculated by one-way analysis of variance and chi-square to test the differences between these two groups.Unadjusted and adjusted hazard ratios(HRs)of thromboembolic events(TEs)were modeled by Cox regression stratified analysis.Results1.The annualized rates of ITP patients for 100 patients-years were 1.28(95%CI:0.83-1.94),0.93(95%CI:0.60-1.43),0.42(95%CI:0.15-1.12)for total,venous and arterial thrombosis.The risk greatly increases with age and particularly for arterial events,with an incidence more than 19 times higher in patients aged>60 than in those<40.The incidence of arterial events and total events for ITP patients aged>60 exceeded 11 times and 5 times than those<40,respectively.2.Age>40 years(P<0.01),previous history of thrombosis(P<0.01),2 or more cardiovascular risk factors at diagnosis(P<0.01),3 or more ITP-specific treatments(P<0.05)were independently associated with an increased thrombosis,before or after the adjustment for confounders.3.Among ITP-specific treatments,the use of rituximab,had shown significantly statistical difference with the incidence of thrombosis after the adjustment for confounders(HR=0.48,95%CI:0.2-1.2,P>0.05),but no statistical difference before the adjustment for confounders(HR=0.21,95%CI:0.1-0.5,P=0.001).No matter before or after the adjustment for confounders,splenectomy and steroids at any time from diagnosis hadn’t reached statistical significance(P>0.05).Conclusion1.Among personal risk factors age>60 is clearly associated with an increased risk of a TE.2.Venous and arterial thromboses are more easily occurred in ITP patients particularly in the following settings,such as patients with a previous blood clot,multiple cardiovascular risk factors,or repeated ITP-specific treatments.3.The use of rituximab could decrease the incidence of TEs,which suggests the drug of rituximab may be used as a protective factor for the prevention of a TE.