Oxidation in Red Cell Disorders and Health Task Force, Department of Clinical Microscopy, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Bangkok, Thailand.
Sci Rep. 2019 Apr 15;9(1):6059. doi: 10.1038/s41598-019-42432-2.
A hypercoagulable state leading to a high risk of a thrombotic event is one of the most common complications observed in β-thalassemia/HbE disease, particularly in patients who have undergone a splenectomy. However, the hypercoagulable state, as well as the molecular mechanism of this aspect of the pathogenesis of β-thalassemia/HbE, remains poorly understood. To address this issue, fifteen non-splenectomized β-thalassemia/HbE patients, 8 splenectomized β-thalassemia/HbE patients and 20 healthy volunteers were recruited to this study. Platelet activation and hypercoagulable parameters including levels of CD62P and prothrombin fragment 1 + 2 were analyzed by flow cytometry and ELISA, respectively. A proteomic analysis was conducted to compare the platelet proteome between patients and normal subjects, and the results were validated by western blot analysis. The β-thalassemia/HbE patients showed significantly higher levels of CD62P and prothrombin fragment 1 + 2 than normal subjects. The levels of platelet activation and hypercoagulation found in patients were strongly associated with splenectomy status. The platelet proteome analysis revealed 19 differential spots which were identified to be 19 platelet proteins, which included 10 cytoskeleton proteins, thrombin generation related proteins, and antioxidant enzymes. Our findings highlight markers of coagulation activation and molecular pathways known to be associated with the pathogenesis of platelet activation, the hypercoagulable state, and consequently with the thrombosis observed in β-thalassemia/HbE patients.
导致血栓事件风险增加的高凝状态是β-地中海贫血/血红蛋白 E 病最常见的并发症之一，尤其是在已接受脾切除术的患者中。然而，高凝状态以及β-地中海贫血/血红蛋白 E 发病机制中这一方面的分子机制仍知之甚少。为了解决这个问题，本研究招募了 15 名未行脾切除术的β-地中海贫血/血红蛋白 E 患者、8 名已行脾切除术的β-地中海贫血/血红蛋白 E 患者和 20 名健康志愿者。通过流式细胞术和 ELISA 分别分析血小板活化和高凝参数，包括 CD62P 和凝血酶原片段 1+2 的水平。进行蛋白质组学分析以比较患者和正常受试者之间的血小板蛋白质组，并通过 Western blot 分析验证结果。β-地中海贫血/血红蛋白 E 患者的 CD62P 和凝血酶原片段 1+2 水平明显高于正常受试者。患者中发现的血小板活化和高凝程度与脾切除术状态密切相关。血小板蛋白质组分析显示 19 个差异点，这些差异点被鉴定为 19 种血小板蛋白，其中包括 10 种细胞骨架蛋白、与凝血酶生成相关的蛋白质和抗氧化酶。我们的研究结果强调了与血小板活化、高凝状态以及随后在β-地中海贫血/血红蛋白 E 患者中观察到的血栓形成相关的凝血激活标志物和分子途径。
