Nomogram For Predicting Portal Vein Thrombosis In Cirrhosis And Analysis Of Platelet Activation Function In Portal Vein Thrombosis

Part Ⅰ:Nomogram for predicting portal vein thrombosis in cirrhosis and prognostic analysisObjective:Portal vein thrombosis(PVT)will aggravate portal venous pressure and lead to portal hypertension related complications,thus seriously affect the prognosis of cirrhotic patients.The aim of this study is to develop a simple and effective model to predict PVT in cirrhotic patients based on nomogram and to verify its prediction value.Besides,we will also perform prognostic analysis to evaluate the survival condition in cirrhotic patients.Methods:Clinical data of 578 cirrhotic patients with or without PVT in The First Affiliated Hospital of Soochow University and The Third Affiliated Hospital of Nantong University were retrospectively collected from January 2017 to August 2022,all patients were divided into training cohort,internal and external validation cohort,and construct predictive nomogram model based on the risk factors for PVT formation.The receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA)were used to evaluate the prediction value of the nomogram model.The feasibility of the model was further validated in internal and external cohorts.All enrolled patients were follow-up to construct the survival curve and calculate the incidence of complications.Results:The independent risk factors for cirrhotic patients with PVT included serum albumin,D-Dimer,portal vein diameter,splenectomy,esophageal and gastric varices after statistical analysis(P<0.05).We used the independent risk factors to construct the nomogram predictive model based on clinical and radioactive feature,the nomogram model had good predictive efficiency for predicting PVT in cirrhotic patients,with an AUC of 0.792 in training cohort(0.761 in internal validation cohort and 0.852 in external validation cohort).The DCA revealed that the nomogram had high level of concordance between different medical centers.There was significant difference between PVT and non-PVT group in survival curve with the P value of 0.039 in training cohort,0.028 in internal validation cohort and<0.001 in external validation cohort by log-rank test.The median survival time of PVT patients in the three cohorts was 43,38,40 months,respectively.The incidence of recurrent esophageal and gastric varices bleeding(EGVB)during the follow-up showed significant difference among three cohorts(P=0.031,0.028,0.001 in training cohort,internal validation cohort and external validation respectively).Conclusion:The nomogram model provides a convenient and feasible way with good efficiency on prediction PVT in cirrhotic patients.Compared with the non-PVT group,cirrhotic patients with PVT were prone to recurrent EGVB and a shorter survival time.Part Ⅱ:Analysis of platelets activation function in cirrhosis with portal vein thrombosisObjective:Platelets are multifunctional effector cells and play the key role in the formation of thrombosis.The study is aimed to explore the platelet activation function in the formation of PVT in cirrhotic patients.Methods:Patients with cirrhosis were recruited in The First Affiliated Hospital of Soochow University from October 2021 to December 2022 and were divided into PVT group and non-PVT group based on radioactive data.Logistic regression analysis was performed to find the risk factors of liver cirrhosis complicated with PVT.Flow cytometry was used to detect the level of CD62p,CD63,monocyte-platelet aggregates(MPA),neutrophil-platelet aggregates(NPA)to evaluate the platelet activation function.Clinical indicators were also evaluated between two groups to find out the potential influence factors.Results:Total 140 subjects were enrolled in our study including 60 cirrhotic PVT patients and 60 cirrhotic non-PVT patients and 20 health volunteers.Multivariate analysis suggested that esophageal gastric varices,splenectomy and D-dimer were independent risk factors for cirrhosis with PVT.The expression of CD41+CD62p+ and CD41+CD63+platelets in PVT group were significant elevated compared with non-PVT group(P<0.05).MPA and NPA showed no statistical difference between two cirrhotic groups.Subgroup analysis showed that the mean fluorescent intensity(MFI)of CD62p and CD63 were associated with portal hypertension related complications(P=0.008,P<0.001),and CD63 MFI was associated with thrombosis burden with statistically significant difference(P=0.019).The CD41+CD62p+and CD41+CD63+platelets as well as MPA and NPA were high-expressed in splenectomy group compared with non-splenectomy group in cirrhotic patients(P<0.05).Positive correlations were found between CD62p MFI with CD63 MFI,MPA as well as NPA(r=0.642,P<0.001;r=0.378,P=0.003;r=0.430,P<0.001).Besides,platelet counts were also correlated with MPA(r=0.556,P<0.001)and NPA(r=0.467,P<0.001).Cirrhotic patients with PVT had higher mortality and were prone to occur portal hypertension related complications in prognostic analysis(P<0.05).Conclusion:Highly activated platelet function exists in patients with cirrhosis,and platelet activation expression was elevated when PVT formation,suggesting that activated platelets may participate in the formation of PVT in patients with cirrhosis.