Serum D-D And MMP-9Level Change Before And After Treatment Of Decompensated Cirrhosis With Portal Vein Thrombosis

Background and objectivePortal vein thrombosis (PVT) is a deep vascular occlusive disease that is rare less seen,mainly occurring in the portal vein, superior mesenteric vein, inferior mesenteric veinor splenic vein. Thrombosis of the portal vein has a close relationship with cirrhosis.According to statistics, about1%of patients with compensated cirrhosis occur toportal vein thrombosis. However, patients with decompensated cirrhosis could reach8%-25%. PVT in decompensated cirrhosis patients always has liver dysfunction andcoagulation disorders, and some patients even lose the chance of surgical treatment.So it is vitally important for this part of patients to adopt reasonable and effectiveanticoagulant therapy. In recent years, the study of anticoagulant drugs is developing.Fondaparinux is a new antithrombotic drug approved by FDA following heparin andlow-molecular-weight heparin. Hardly any interactions are identified betweenfondaparinux and platelets. And fondaparinux doesn’t affect bleeding time, and thebioavailability can be close to100%by hypodermic injection with a half-life of about17hours. Therefore, fondaparinux can be used in a fixed dose without anticoagulationmonitoring. At present there is no report related to fondaparinux application in cirrhosis patients with portal vein thrombosis, but according to the principle offondaparinux, it will have a good anticoagulant effect and can promote therecanalization of portal vein.The D-dimer (D-D) is a sensitivity index for detecting thrombosis in clinicalwork and has been accepted both at home and abroad. It is one of molecular markersrepresenting the formation and degradation of fibrin. At the states of hypercoagulation,micro-thrombus thrombosis and increased fibrinolytic activity, the concentration ofD-dimer will be rising. Matrix metalloproteinase-9(MMP-9) always involve in thedynamic balance of extracellular matrix (ECM) and tissue remodeling. It plays animportant role in the process of tissue damage and healing. MMP-9can participate inthe remodeling of blood vessel endothelium by releasing vascular endothelial growthfactor (VEGF). As a specific inhibitor of MMP-9, tissue inhibitor ofmetalloproteinase-1(TIMP-1) can bind specifically to MMP-9forming complexes andinhibit the activity of MMP-9.The research chose patients with decompensated cirrhosis and with fondaparinuxanticoagulant therapy as research objects. Serum D-D、MMP-9and TIMP-1weredetected before and after anticoagulant therapy to analyze the expression and thecorrelations between the three indexes, which may help us to further discuss themechanism of decompensated cirrhosis with portal vein thrombosis. Meanwhile, theefficacy and safety of fondaparinux can be further validated, which may provide abrief guide for related clinical work.MethodAfter a clear diagnosis and excluding related contraindications,22patientsapplied fondaparinux sodium (2.5mg q24hr subcutaneously) in the region of theumbilicus under the basis of conventional liver protection therapy. The therapeuticregimen lasted until portal vein recanalization. And then patients were prescribedalternate anti-platelet aggregation (aspirin enteric-coated tablets,100mg q24hr). Inthe process, we chose pre-treatment，portal vein recanalization and one month afterportal vein recanalization as three observation time points. Platelet count (PLT), prothrombin time (PT), international normalized ratio (INR), liver function weremeasured, and the results of portal vein color Doppler ultrasound were collected.Serum in the three time points was collected as experimental specimens. ELISA wasapplied to detect the expression of D-D, MMP-9and TIMP-1.Statistical analysis: All the dates were analyzed by SPSS17.0statistical package,measurement data were expressed by standard deviation. The mean among moregroups uses the ANVOA. The relation of two variables was analyzed by theSpearman correlation analysis. α=0.05is considered as significance.Results1. After treatment,22patients got satisfactory treatment effect and reached portalvein recanalization. There was no recurrence of portal vein thrombosis after onemonth reexamination.2. Before and after treatment, Plt, PT and INR have no significant differences.There was no obvious abnormity about liver function. Only2patients appearedecchymoses at the injection site. No other adverse reactions were observed.3. As portal vein recanalization, the expression of serum D-D, MMP-9and TIMP-1are higher than those in pre-treatment, the differences are significant (P﹤0.05),No e significant difference was observed compared portal vein recanalizationwith after one month reexamination(P＞0.05).4. Serum D-D and MMP-9, D-D and TIMP-1and MMP-9and TIMP-1have goodpositive correlation. The correlation coefficient before treatment is greater thanthat after treatment.Conclusions1. The concentrations of D-D, MMP-9and TIMP-1are higher but declining afteranticoagulant therapy in decompensated cirrhosis with portal vein thrombosis.The state might be a hint that D-D, MMP-9and TIMP-1could give a judgementto advances of thrombosis and the effective rate of anticoagulant therapy.2. Serum D-D and MMP-9have good positive correlation in patients with PVT，and the both may be used as reaction factors in decompensated cirrhosis with portalvein thrombosis.3. The expression of TIMP-1and MMP-9before and after treatment is different.The influence factors may be complex, and need to be further studied.4. The results of clinical observation show fondaparinux is effective and secure fordecompensated cirrhotic with portal vein thrombosis, and has no side effects liverfunction or thrombocytopenia.