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

Abstract

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 β-thalassemia major (β-TM), β-thalassemia intermedia (β-TI), α-thalassemia intermedia (α-TI) and combined α-/β-thalassemia (α + β-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 β-TM, β-TI, and α-TI than in controls (p < 0.005). PC activity was lower in β-TM than in α-TI (p = 0.004). PS antigen was elevated in β-TM (p = 0.011) and sEPCR was elevated in α-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 α + β-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. 1. Introduction Mutations or deletions of globin genes in thalassemia result in an imbalance of globin synthesis, decreased erythropoiesis, and extravascular hemolysis. Hypercoagulability states are common occurrences in thalassemia patients in southeast Asia, the Mediterranean, and the Middle East regions [1-3]. The prevalence of β-thalassemia is approximately 4.91% and that of α-thalassemia is about 14.13% in the Guangxi province of China, and the various causes of coagulation disorders deserve investigation [4]. Accumulation of unmatched globin chains results in premature destruction of erythrocyte precursors in bone marrow, hemolysis of erythrocytes in the peripheral blood, and the appearance of abnormal red blood cells (RBCs). Loss of deformability impairs passage of RBCs through capillaries [5], and the resulting hemostasis may elicit a procoagulant condition [6]. Other reasons may include endothelial injury, platelet activation, increased plasma microparticles, impaired nitric oxide bioavailability, increased blood oxidants, and phosphatidylserine exposure on the outer ...

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Heparanase Level and Procoagulant Activity Are Increased in Thalassemia and Attenuated by Janus Kinase 2 Inhibition

“…1 Coagulation system activation markers, including low levels of proteins C and S, and increased thrombinantithrombin levels, were observed in these patients. 20 Regular transfusions were found to decrease the risk of thrombosis, whereas splenectomy significantly increased such risk. 1 Along with thrombocytosis that frequently occurs after splenectomy, Trinchero et al 21 reported a prothrombotic state in splenectomized patients, characterized by enhanced platelet activation.…”