Clinical Features And Risk Factors In Patients With Lymphoma Complicated With Venous Thromboembolism

ObjectiveThere is a higher risk of lymphoma patients with venous thromboembolism(VTE),which not only affects patients activity,delays chemotherapy,and is even associated with worsening survival.It is highly consequential for patients with high VTE risk to identify,monitor and prevent early.However,the predictive accuracy of lymphoma specific risk scores has not been consistently confirmed.Sensitive risk indicators are still needed to be defined by multi-center analysis for optimizing risk assessment tools.The purpose of this study is to analyze the clinical characteristics and risk factors of lymphoma patients complicated with venous thromboembolism for strengthening clinicians’ awareness of VTE and providing potential variables for optimization of risk model.MethodsClinical data of 1750 inpatients with lymphoma treated with at least 1 cycle of chemotherapy within the first hospital of Jilin university from January 2013 to December 2019 were collected for retrospective analysis.The overall incidence of thrombosis and the characteristics of arteriovenous distribution were analyzed.A total of 112 patients with VTE events were selected in the VTE group,and 243 patients without VTE events were randomly selected as control group.Then we analyzed the vascular distribution,occurrence time and anticoagulant drugs in VTE group and compared the potential risk factors between the two groups.Factors include: 1)individual factors of patients: age at first visit,gender,BMI index,complications(hypertension,diabetes,coronary heart disease/cardiac insufficiency,chronic renal insufficiency),ECOG score,VTE/myocardial infarction/stroke history,smoking history,indwelling PICC catheter or not,history of surgical treatment under general anesthesia within one month.2)disease related characteristic of patients: lymphoma subtype,stage,with or without B symptoms,extranodal organ infiltration,mediastinal involvement,central or bone marrow involvement,bulky disease(>10cm),prognosis score and efficacy evaluation.3)baseline test indexes: lactate dehydrogenase(LDH),β2-microglobulin,albumin number(ALB),prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(FIB),white cell count(WBC),neutrophil count(NE),hemoglobin(HGB)and platelet count(PLT).SPSS 26.0 software was used for statistical analysis,and the significant variables were included in multivariate Logistic regression analysis.P<0.05 for significance.ResultsAmong the 1750 patients with lymphoma,there were 163 thrombotic events(including arterial thrombosis,VTE and superficial venous thrombosis).The total incidence of thrombosis was 9.3%.Obviously venous thrombosis events were higher than arterial events.The incidence of VTE events was 6.8%,mainly deep venous thrombosis,and only 5 cases(4.2%)of pulmonary embolism.VTE often occurs in the deep vein of the limb,the lower limb is more than the upper limb,and the intermuscular vein,axillary vein and subclavian vein are more common.Catheter-related thrombosis accounts for 33.0%.The occurrence time of VTE was mainly concentrated within 1 month after the diagnosis of lymphoma(58.0%).80.3%of patients developed VTE within 3 months of diagnosis,and 25.9% of patients had VTE events before the first chemotherapy.VTE was mainly treated with low molecular weight heparin or rivaroxaban,and no patients were treated with unfractionated heparin and other direct oral anticoagulants.Univariate analysis showed that the median age of patients in the VTE group was 62.5 years,which was significantly higher than that of 54 years in the control group(P<0.001).Patients with hypertension,coronary heart disease/cardiac insufficiency or chronic renal insufficiency had a higher incidence of VTE than those in the control group.Patients with a previous history of VTE/ myocardial infarction/ stroke also had a higher risk of VTE(P=0.001).The percentage of patients with ECOG score ≥ 2 in the VTE group was 32.1%,which was higher than that in the control group(18.5%)(P=0.004).The proportion of patients with indwelling PICC catheter in the VTE group was also significantly higher than that in the control group.There were 9 HL patients(8.0%),97 aggressive NHL patients(86.6%)and 6 indolent NHL(5.4%).In the control group,there were 30 HL patients(12.3%),179 aggressive NHL patients(73.7%)and 34 indolent NHL(14.0%).The proportion of patients with aggressive NHL in VTE group was obviously higher than that in control group,while the proportion of patients with indolent NHL was lower than that in control group.Pairwise comparison showed that there was significant difference between aggressive NHL and indolent NHL.The proportion of patients with late disease stage(III/IV stage)and high-risk of prognosis was also different between the two groups.There were more patients with later stage and higher risk of prognosis in VTE group(stage: P=0.008;prognosis: P=0.001).The number of patients with extranodal organ infiltration in the VTE group was 84(75.0%),which was significantly higher than that in the control group(54.3%)(P=0.001).There was no significant difference in the level of baseline blood cells between the two groups.The proportion of LDH > 250U/L,β 2-microglobulin >2.5mg/L,ALB < 40g/L in VTE group was significantly higher than that in control group(P<0.05).The combination of bulky disease,mediastinal involvement central involvement and meaningful factors in single factor analysis were included in the binary Logistic regression model.Multivariate analysis showed that advanced age,chronic renal insufficiency,indwelling PICC catheter,mediastinal involvement,baseline LDH > 250U/L were independent risk factors for VTE in patients with lymphoma.For every 1 year increased in age,the risk of VTE increased by 3.8%(OR=1.038).The risk of VTE in patients with chronic renal insufficiency was 3.8times higher than that in patients without this complication(OR=3.810).The risk of VTE in patients with PICC catheterization was twice as high as that in patients without catheterization(OR=2.182).The risk of VTE in patients with mediastinal involvement was 1.8 times higher than that without mediastinal involvement(OR=1.864).The risk of VTE in patients with baseline LDH > 250U/L was twice as high as in patients with LDH ≤ 250U/L(OR=2.064).The study also compared theefficacy evaluation of disease between the two groups,showing no significant difference in objective response rate and complete response rate at half a year.In addition,there was no difference in patients with high risk in Khorana score between the two groups.The proportion of patients with intermediate or high risk in Thro Ly score accounted for 69.6% in the VTE group and 53.5% in the control group.There was a statistical difference between the two groups(P=0.004).The positive predictive value is 37.5%,the negative predictive value is 76.9%,the sensitivity is 69.6%,and the specificity is 46.5%.Conclusion1.The incidence of thrombotic events in lymphoma patients receiving chemotherapy was 9.3%.The incidence of VTE was 6.8%.The incidence of venous thrombotic events was significantly higher than that of arterial thrombotic events.2.Lymphoma with VTE events occurred in the first 3 months after diagnosis,and 25.9% of patients had VTE events before the first chemotherapy.3.Aggressive NHL has a higher incidence of VTE than indolent NHL,and the difference is statistically significant.4.Advanced age,chronic renal insufficiency,indwelling PICC catheter,mediastinal involvement,baseline LDH > 250U/L were independent risk factors for lymphoma complicated with VTE.5.Thro Ly score is better than Khorana score in predicting VTE of lymphoma,but it needs to be further optimized.