Part One: Analysis Of Thrombosis And Related Risk Factors In Chinese Adult Patients With Primary Immune Thrombocytopenia. Part II: Clinical Analysis Of Eltropapax In The Treatment Of Primary Immune Thrombocytopenia

The incidence and risk factors for thrombosis in Chinese adults with primary immunethrombocytopeniaBackground As the most common acquired hemorrhagic disease,primary immune thrombocytopenia(ITP)has also been reported to have higher incidence rate of thrombosis than the normal population.There were few literatures related to ITP complicated with thrombosis has been reported.Rodeghiero F summarizes some literatures that the incidence of arterial thrombosis is about 1.14-4.1%and venous thrombosis is about 0.41-2.9%in ITP patients.Because the occurrence of thrombosis varies with ethnicity and region,and the occurrence of thrombosis affects the treatment of patients with ITP,especially those with thrombocytopenia.So our study was conducted to understand the occurrence of thrombosis and related risk factors in Chinese ITP population.Objective To explore thrombosis and related risk factors in Chinese adults with ITP,And provide the basis for the prevention strategy of ITP patients with thrombosis and assist clinicians in developing target treatment plans,balancing the risk of bleeding and thrombosis.Methods We retrospectively analyzed of 3225 ITP patients hospitalize in the Blood Disease Hospital,CAMS&PUMC from October 2005 to December 2017.There are 1309 males and 1916 females,with a median age of 30 years(from 4 months to 94 years).None of the 1,008 children(<18 years old)had thrombosis;there were 2217 adult patients(>18 years old).The basic information of patients was collected through the medical record retrieval system of our hospital,all thrombosis events were recorded,and personal information,laboratory data and the treatment were collected.A total of 46 cases of thrombotic events occurred.Since no thrombotic events occurred in children,according to the information collected,the adult patients were divided into thrombosis group and non-thrombosis control group,and analyzed the cause,diagnosis,treatment and prognosis.Single factor analysis of variance(continuous variable)and chi-square test(categorical variable)were used to compare the indexes between the two groups.Preliminary analysis found that thrombotic events has obvious age distribution,adjust the confounding factors,the SPSS system was used to conduct 1:2 frequency matching according to the patient's gender,age and the ITP history,matching thrombus group 45 cases and control group 90 cases respectively,the effect of different risk factors on thrombosis was assessed by binary classification multi-factor logistic regression analysis.Results1.A total of 46 patients had a thrombotic event with a prevalence of 1.43%(46/3225 cases).The median age of thrombosis was 54 years old(26 to-83 years old),the prevalence of thrombosis was 3.37%(40/1187 cases)in>40 years old,which was significantly higher than 0.58%(6/1030 cases)in those under 40 years old,there was a statistically significant difference,P=0.00.There was no statistical difference in the incidence of thrombosis between males and females,1.53%(20/1309)vs 1.36%(26/1916),P=0.187.The prevalence of arterial thrombosis was 1.12%(36/3225),which was higher than venous thrombosis 0.22%(7/3225),P=0.00;and 82.61%(38/46 cases)of patients had PLT<100�109/L.2.All adult patients were divided into thrombosis group(46 cases)and non-thrombosis group(2,171 cases),through a comparative analysis of thrombotic risk factors found that age,smoking,hypertension,diabetes and post-splenectomy are independent risk factors for thrombosis in ITP patients,P values were 0.00?0.002,0.00,0.001 and 0.022,respectively.There was no statistical difference in the presence or absence of thrombotic events whether received glucocorticoid or TPO/TPO-Ra treatment,the P values were 0.232 and 0.531,respectively.3.Adjust for confounding factors,45 cases in the thrombosis group and the non-thrombosis group 90 cases were matched with a 1:2 randomized control group.A history of hypertension was found to be risk factors for thrombosis in ITP patients by binary logistic regression analysis,OR=2.523,95%Cl(1.106 5,755),P=0.028.Family history of thrombosis and cardiovascular and cerebrovascular diseases increases the risk of thrombosis,OR=4.667,95%CI(0.99-21.99),P=0.051.Conclusions1.For Chinese ITP population,ITP maybe also an immune disease accompanied by thrombosis.Thrombosis can occur even if platelet count<100�109/L.2.The thrombotic events of ITP are mainly arterial thromboembolism,and the embolic sites are mostly cerebrovascular.3.With the increase of age,the risk of thrombosis increases,and the peak age is 51-60 years old.4.The incidence of thrombosis in male patients was slightly higher than that in female patients,but overall comparison showed that gender was not a risk factor for thrombosis.5.Risk factors for cardiovascular events,including smoking,hypertension and diabetes,increase the risk of thrombosis in ITP patients,hypertension is an independent risk factor for thrombosis.6.the risk of thrombosis in patients receiving splenectomy should be paid attention to clinically.Treatment with glucocorticoid and TPO did not promote thrombotic events.Clinical analysis of eltrombopag in the treatment of primary immune thrombocytopeniaObjective:To investigate the effect and safety of eltrombopag for the treatment of primary immune thrombocytopenia(ITP)in Chinese adults.Methods:We retrospectively analysed of 75 ITP patients hospitalize in the Blood Disease Hospital,CAMS&PUMC from February 2013 to October 2018,the clinical data of treated with eltrombopag were analyzed.Results:1.A total of 75 patients including 25males and 50 females,with a median age of 44 years(from 19 to 66 years),the median platelet count before treatment was 13(1-66)� 109/L,12 patients were treated with other drug before the treatment with eltrombopag,therefore,the PLT>30 x 109/L at baseline,the median PLT of patients at week 2,week 4,month 3 and the six months after treatment were 29(1-286)�109/L,57(3-616)�109/L,67(3-300)�109/L,and 92(10-397)�109/L,and the platelet level after treatment was significantly higher than before treatment,P=0.00.The median time to platelet recovery?30�10~9/L at the first time after treatment was 14 days(3-42days),54.67%(41/75 cases)were effective within 2 weeks.The total response rate was 81.33%(61/75 cases),32%of the patients(24/75cases)had response more than 6 months,and in 10 patients,the platelet count remained>30 x 109/L for at least half a year after the discontinuation of treatment.2.Use the drug according to the treatment regimen,the response rate of both 50mg/d and 75mg/d groups was higher than that of 25mg/d group(45.45%vs 22.22%and 65.52%vs 22.22%,P<0.05).By analyzing possible correlation factors affecting the effective dose of the drug,we found that the value of weight and BMI of the patients had no significant correlation between the effective dose,P>0.05.As to analyze the possible factors affecting drug efficacy,36 of the 75 patients received TPO treatment(11 cases were effective in TPO treatment),and 39 patients did not receive TPO treatment,the results showed that there was no statistically significant difference in the efficacy of TPO or with or without the previous treatment of TPO,60%vs 56.52%,58.33%vs 66.67%,P>0.05;the response rate of patients with specific autoantibodies against platelet glycoprotein positive contrast with the negative group were not different(P>0.05);the number of megakaryocytes in all patients was normal or increased,and there were no statistically significant difference in the therapeutic efficiency between the normal group and the increased group(87.88%,76.19%),P>0.05.3.Adverse events that occurred more frequently due to eltrombopag included increased transaminase(22/37cases)and blood bilirubin(11/37cases).All liver adverse events return to normal or return to baseline after treatment;Other adverse events include nausea,lower limb edema,hypoalbuminemia,dizziness,and cerebral infarction associated with thrombocytopenia.Conclusions:1.Eltrombopag is an effective and safe treatment option for ITP,and liver function damage as the most common adverse events.2.In order to rapidly improve platelet level and minimize the hemorrhage risk associated with decreased platelet counts,we advise the recommended initial dose is 50mg per day for adult patients,and combined with hepatoprotective therapy.3.The following items had not affect the effection of eltrombopag,whether rhTPO was effective,abnormal expression of platelet autoantibodies or more megakaryocytes.4.Because there was no curative effect soon after the drug was discontinued,it is suggested to try to gradually reduce the dose until the drug was withdraw.