Alteratiods Of Anticoagulant Proteins And Soluble Endothelial Protein C Receptor In Thalassemia Patients

Objective To detect the antigen concentration and activity level in proteins related to the protein C pathway in patients with thalassemia.To investigate the relationship of these proteins with the hypercoagulability and/or thrombosis in thalassemia.Methods A group of 122 patients with thalassemia were compared with 32 gender-and age-matched controls.Thalassemic patients consisted of 67 ?-thalassemia major(?-TM),22 ?-thalassemia intermedia(?-TI)and 33 ?-thalassemia intermedia(?-TI)patients.Antigen concentration of protein C(PC),protein S(PS),antithrombin III(AT III),soluble endothelial protein C receptor(sEPCR),thrombin-antithrombin complex(TAT),and intercellular adhesion molecule1(ICAM-1)were measured by enzyme-linked immunosorbent assay.PC and AT III were assayed by substrate chromatography.PS activity was detected by a prothrombin time(PT)-based free protein S assay.Results(1)Proteins related to the protein C pathway: PC and PS activity below normal range were seen in 117(95.9%)and 93(76.2%)patients with thalassemia,respectively.The plasma activity levels of anticoagulant protein(PC,PS and AT III)in the subgroups of thalassemia were significantly lower than those in the control group(P<0.006).Concomitant reductions in PC and AT III antigen and activity were observed in ?-TM,?-TI,and ?-TI than in controls(P<0.009).PC activity was lower in ?-TM than in ?-TI(P=0.004).PS antigen was elevated in ?-TM(P=0.012)and sEPCR was elevated in ?-TI(P=0.008).(2)Thrombosis and endothelial injury markers: TAT and ICAM-1 was increased in all patient subgroups compared with controls(P<0.001).ICAM-1 was increased in patients with splenectomy(P=0.010).(3)Factors related to splenectomy: Nonsplenectomized patients had lower PC(P=0.001)and PS(P=0.015)activity and higher sEPCR(P<0.001)than postsplenectomy patients.ICAM-1(P=0.010)and platelet count(P<0.001)in splenectomy group were elevated than those in non-splenectomy group.No statistically significant difference was conserved in TAT.(4)Factors related to transfusion: Transfusion dependent thalassemia(TDT)patients had lower both antigen(P=0.004)and activity(P=0.002)PC levels than those with nontransfusion dependent thalassemia(NTDT).Compared to TDT patients,the levels of serum ferritin(P<0.001)and fibrinogen(P=0.008)were significantly increased and APTT(P=0.008)prolonged significantly in patients with TDT.No statistically significant difference was conserved in TAT or ICAM-1.(5)Pearson correlation: The anticoagulation activity and antigen level of PC and AT III were positively correlated.Significantly,positive correlations of the activity levels of PC and PS were seen.The activity of PC was positively correlated with antigen and activity of AT?.sEPCR was positively correlated with PS antigen level,TAT and ICAM-1,and negatively correlated with AT III activity level.TAT was inversely correlated with PC activity(r=-0.225,p=0.005),and positively correlated with sEPCR(r=0.462,p<0.001)and serum ferritin(r=0.229,p=0.011).ICAM-1 was inversely correlated with PC(r=-0.350,p<0.001),PS(r=-0.283,p<0.001),and AT III(r=-0.295,p<0.001)activity and positively correlated with sEPCR(r=0.167,p=0.038)and serum ferritin(r=0.227,p=0.012).Serum ferritin was positively correlated with TAT(r=0.229,p=0.011)and ICAM-1(r=0.227,p=0.012).Conclusions Patients with ?-TM,?-TI,and ?-TI had chronic hypercoagulability and endothelial cell activation and the hypercoagulability of thalassemia was multifactorial.The difference of antigen concentration and activity level of anticoagulant protein meant that the changes in anticoagulant protein were not only due to anticoagulant consumption.Deficiencies of activity in anticoagulant proteins(PC,PS and AT III)and elevated sEPCR may contribute to chronic hypercoagulability in thalassemia patients.