Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province 530021, China.
Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province 530021, China.
Thromb Res. 2018 Dec;172:61-66. doi: 10.1016/j.thromres.2018.10.016. Epub 2018 Oct 18.
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.
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.
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.
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.
地中海贫血的特征是一种高凝状态，其中蛋白 C (PC) 途径控制血栓形成。我们研究了地中海贫血中 PC、蛋白 S (PS)、抗凝血酶 III (AT III) 和可溶性内皮蛋白 C 受体 (sEPCR) 的变化。
一组 129 名β-地中海贫血重型 (β-TM)、β-地中海贫血中间型 (β-TI)、α-地中海贫血中间型 (α-TI) 和α-/β-地中海贫血联合型 (α+β-地中海贫血)患者与 32 名性别和年龄匹配的对照组进行比较。通过酶联免疫吸附试验测定 PC、PS、AT III、sEPCR、凝血酶-抗凝血酶复合物 (TAT)和细胞间黏附分子 1 (ICAM-1)抗原。通过基质色谱法和基于凝血酶原时间 (PT)的游离蛋白 S 测定法测定 PC、AT III 和 PS 活性。
95.3%的患者存在 PC 缺陷，77.5%的患者存在 PS 缺陷。与对照组相比，β-TM、β-TI 和 α-TI 患者中同时存在 PC 和 AT III 抗原和活性降低（p<0.005）。与 α-TI 相比，β-TM 中的 PC 活性较低（p=0.004）。β-TM 患者 PS 抗原升高（p=0.011），α-TI 患者 sEPCR 升高（p=0.018）。未行脾切除术的患者 PC（p=0.001）和 PS（p=0.006）较低，sEPCR 较高（p=0.021）。与非输血依赖型地中海贫血（NTDT）患者相比，输血依赖型地中海贫血（TDT）患者的 PC 水平较低（p<0.005）。亚组患者的 ICAM-1 增加（p<0.001），尤其是脾切除术患者（p=0.009），所有患者亚组的 TAT 与对照组相比均升高（p<0.001），但α+β-地中海贫血患者除外。
抗凝蛋白缺乏和 sEPCR 升高导致这些中国起源的地中海贫血患者出现慢性高凝状态。脾切除术缓解了该患者队列中这些变化，脾切除术中位时间为两年。输血对于避免血栓形成并不理想。
