Alterations of anticoagulant proteins and soluble endothelial protein C receptor in thalassemia patients of Chinese origin

Background: Thalassemia is characterized by a hypercoagulable state in which the protein C (PC) pathway controls thrombosis. We investigated changes in PC, protein S (PS), antithrombin III (AT III) and soluble endothelial protein C receptor (sEPCR) in thalassemia. Methods: A group of 129 patients with beta-thalassemia major (beta-TM), beta-thalassemia intermedia (beta-TI), alpha-thalassemia intermedia (alpha-TI) and combined alpha-/beta-thalassemia (alpha + beta-thal) were compared with 32 gender-and age-matched controls. PC, PS, AT III, sEPCR, thrombin-antithrombin complex (TAT), and intercellular adhesion molecule1 (ICAM-1) antigens were measured by enzyme-linked immunosorbent assay. PC, AT III, and PS activity were assayed by substrate chromatography and a prothrombin time (PT)-based free protein S assay. Results: PC deficiency was seen in 95.3% of the patients and PS deficiency was seen in 77.5%. Concomitant reductions in PC and AT III antigen and activity were observed in beta-TM, beta-TI, and alpha-TI than in controls (p < 0.005). PC activity was lower in beta-TM than in alpha-TI (p= 0.004). PS antigen was elevated in beta-TM (p = 0.011) and sEPCR was elevated in alpha-TI (p= 0.018). Nonsplenectomized patients had lower PC (p= 0.001) and PS (p = 0.006) and higher sEPCR (p = 0.021) than postsplenectomy patients. Transfusion dependent thalassemia (TDT) patients had lower PC levels (p < 0.005) than those with nontransfusion dependent thalassemia (NTDT). ICAM-1 was increased in patient subgroups (p < 0.001), especially those with splenectomies (p= 0.009), and TAT was increased in all patient subgroups compared with controls (p < 0.001) except for alpha + beta-thal. Conclusions: Deficiencies of anticoagulant proteins and elevated sEPCR contributed to chronic hypercoagulability in these thalassemia patients of Chinese origin. Splenectomy alleviated these alterations in this patient cohort with the median duration since splenectomy of two years. Blood transfusion was not ideal for avoiding thrombosis.