Association Between D-dimer Level And Portal Venous System Thrombosis In Liver Cirrhosis: Meta-analysis And Retrospective Observational Study

BackgroundLiver cirrhosis is a common disease in the digestive system,which has a high mortality rate.Portal vein thrombosis(PVT)is one of the severe complications of liver cirrhosis and can contribute to significant morbidity and mortality.Early detection and prevention of PVT may improve the prognosis of patients with liver cirrhosis.Development of PVT is associated with systemic prothrombotic factors and local risk factors,including coagulation factor mutation,anticardiolipin antibodies,high with hyperhomocysteinemia,platelet count and function change,fibrinolysis system abnormalities,a variety of inflammatory injury,portal vein hemodynamic changes.D-dimer is produced under the action of the fibrinolytic enzyme during the fibrinolysis,mainly reflecting the function of fibrinolysis.D-dimer testing is cheap and readily available in clinical practice to assist the diagnosis of venous thrombosis.Negative D-dimer combine with low clinical probability tools can effectively rule out the diagnosis of deep vein thrombosis and pulmonary embolism.whether D-dimer is the independent risk of the PVT is controversial.Aims we performed a meta-analysis and retrospective study further exploration the role of D-dimer in cirrhotic patients with PVT.Methods1: All papers were searched via Pub Med,EMBASE,China National Knowledge Infrastructure,Wan Fang,and VIP databases.Search items were listed as follows:(“d-dimer”[All Fields])AND(“liver cirrhosis” [All Fields])AND(“portal vein thrombosis” [All Fields]).The last search was performed on July 20,2014.D-dimer were collected and presented with mean±standard deviation,A standardized mean difference(SMD)with 95% confidence interval(CI)was pooled.Heterogeneity between studies was assessed by using the I2 statistic and the ?2 test.The Egger test was performed to evaluate the presence of publication bias.All analyses were conducted using Stats Direct statistical software version 2.7.8(Stats Direct Ltd,Sale,Cheshire,UK).2: The retrospective study included 66 patients who were admitted to the General Hospital of the Shenyang military between July 2011 and June 2014.Demographic data,the diagnosis of liver cirrhosis,the etiology of cirrhosis,clinical manifestations,abdominal imaging examination,laboratory data,splenectomy and laboratory data were collected.laboratory data including regular blood test,liver function,renal function,blood coagulation,serum albumin and serum ion.Child-Pugh classification and scores were calculated.Continuous data were presented with mean±standard deviation and were compared by using the independent sample t tests.Categorical data were expressed as frequency,P value <0.05 was of statistically significant.Receiver operating curve(ROC)was employed to evaluate the specificity and sensitivity of D-dimer for predicting the presence of PVT.Areas under ROC(AUROC)with 95%confidence interval(CI)were calculated.P value <0.05 was of statistically significant.All statistical analyses were performed by using the Med Calc software.Results1: Overall,284 studies were initially identified,of which 21 were included.Cirrhotic patients with PVT had a significantly higher D-dimer concentration than those without PVT(pooled SMD = 1.249,95%CI = 0.740–1.758).After the portal Hypertension related surgery,cirrhotic patients with PVT had a similar preoperative D-dimer concentration to those without PVT(pooled SMD = 0.820,95%CI =-0.122–0.286),but a higher postoperative value of D-dimer concentration than those without PVT(pooled SMD = 2.505,95%CI = 0.975–4.036).Notably,the D-dimer concentration at the 1st postoperative day was similar between cirrhotic patients with and without PVT(pooled SMD = 0.137,95%CI =-0.827–1.101),but that at the 7th postoperative day was higher in cirrhotic patients with PVT than in those without PVT(pooled SMD = 1.224,95%CI = 0.277–2.171).2: Of the 66 included patients,mean D-dimer level was 0.51±0.72 ?g/mL(range:0.10-3.44).Mean D-dimer level was not significantly different between PVT and non-PVT groups(0.68±0.93 ?g/m L versus 0.41±0.56 ?g/m L,P=0.146).Area under the receiver operating curve for D-dimer level for predicting the presence of PVT was 0.606(95% confidence interval: 0.478-0.724,P=0.1393).The optimal cut-off value for D-dimer was 0.22 with a sensitivity of 58.3% and a specificity of 69.0%.The subgroup analyses of patients without splenectomy or those with different Child-Pugh classes demonstrated no significant difference in the D-dimer level between PVT and non-PVT groups.Conclusion1.The meta-analysis found that D-dimer might be regarded as a diagnostic marker for PVT in liver cirrhosis.In addition,postoperative D-dimer testing is worthwhile for the diagnosis of PVT after portal hypertension related surgery.However,the specific time and the critical value of the D-dimer also need to be further studied.2.The retrospective study found that the mean D-dimer level in PVST group higher than non-PVST groups.However,there was not significantly different between them,indicating that D-dimer may not be a useful factor in PVT prediction.3.The meta-analysis and retrospective study's conclusions are not consistent.The reasons should be: 1)low quality of literature included in the meta-analysis study,2)sample and methods to retrospectively collected data in the retrospective study.D-dimer was not a reliable risk factor for PVT.Further well-designed prospective study should be necessary to confirm this finding.