Hemprachitchai Nutthida, Praneetponkang Rattanaporn, Wongwerawattanakoon Pakawan, Wongborisuth Chokdee, Innachai Pawarit, Kadegasem Praguywan, Khlangtan Tanyanee, Sriwantana Thanaporn, Phoonlapdacha Phanphen, Dumrongwongsiri Oraporn, Chuansumrit Ampaiwan, Pattanapanyasat Kovit, Sirachainan Nongnuch, Sibmooh Nathawut, Chaichompoo Pornthip, Songdej Duantida
Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchatewi District, Bangkok, 10400, Thailand.
Graduate Program in Molecular Medicine, Faculty of Science, Mahidol University, Bangkok, Thailand.
BMC Pediatr. 2025 May 20;25(1):405. doi: 10.1186/s12887-025-05741-2.
Patients with thalassemia acquire cellular oxidative damage mainly from the degradation of excessive uncoupled hemoglobin (Hb) chains and iron overload. The oxidative damage of red blood cells (RBCs) and platelets potentially results in the worsening of ineffective erythropoiesis, hemolysis, and the occurrence of thromboembolic events. Vitamin E (VitE) is an antioxidant that inhibits membrane lipid peroxidation. It is widely used as a supplement in thalassemia; however, its benefits in improving cellular oxidative damage remain unclear.
We conducted a double-blind, randomized, controlled trial registered in the Thai Clinical Trials Registry (TCTR20220801001) on 01/08/2022. We randomized transfusion-dependent (TD) β- and α-thalassemia (aged 10-25 years) to receive oral VitE 400 IU/day or placebo at a 1:1 ratio for 6 months. Cellular oxidative damage markers, including phosphatidyl serine (PS)-bearing RBCs, PS-bearing RBC vesicles, PS-bearing platelets, PS-bearing microparticles (MPs), PS-bearing RBC-MPs, PS-bearing platelet MPs (PMPs) and platelet activation, were measured before and after the intervention as the primary outcomes.
Seventy-four TD thalassemia patients were categorized into 63 β-thalassemia (10 splenectomy, β-Thal-S; and 53 non-splenectomy, β-Thal-NS) and 11 α-thalassemia (non-splenectomy, α-Thal-NS). Randomized from all patient groups, 36 received VitE and 38 received a placebo. A significant reduction in PS-bearing RBCs and PS-bearing RBC vesicles was observed in the β-Thal-NS receiving VitE. This occurred parallel with a substantial decrease in malondialdehyde levels, as a marker of lipid peroxidation, found only in the β-Thal-NS but not in β-Thal-S and α-Thal-NS groups. In the β-Thal-NS group, VitE had improved RBC pathology as demonstrated by the inverse correlation between post-treatment VitE levels and PS-bearing RBCs (p = 0.001) as well as reticulocyte count (p = 0.006), although Hb levels remained unchanged. The VitE treatment did not result in improving platelet pathology or reducing MPs. No adverse event was reported in both VitE and placebo groups.
VitE 400 IU/day was well-tolerated and associated with improved oxidative damage of the RBCs in TD β-Thal-NS patients. Accordingly, advice for VitE supplementation in young TD β-Thal-NS patients can be beneficial.
地中海贫血患者的细胞氧化损伤主要源于过量解偶联血红蛋白（Hb）链的降解和铁过载。红细胞（RBC）和血小板的氧化损伤可能导致无效造血、溶血恶化以及血栓栓塞事件的发生。维生素E（VitE）是一种抗氧化剂，可抑制膜脂质过氧化。它在地中海贫血中被广泛用作补充剂；然而，其在改善细胞氧化损伤方面的益处仍不明确。
我们于2022年8月1日在泰国临床试验注册中心（TCTR20220801001）进行了一项双盲、随机、对照试验。我们将输血依赖型（TD）β-和α-地中海贫血患者（年龄10 - 25岁）按1:1的比例随机分为两组，一组每天口服400 IU VitE，另一组服用安慰剂，为期6个月。作为主要结局指标，在干预前后测量细胞氧化损伤标志物，包括携带磷脂酰丝氨酸（PS）的RBC、携带PS的RBC囊泡、携带PS的血小板、携带PS的微粒（MP）、携带PS的RBC - MP、携带PS的血小板微粒（PMP）以及血小板活化情况。
74例TD地中海贫血患者被分为63例β-地中海贫血（10例脾切除，β-Thal-S；53例非脾切除，β-Thal-NS）和11例α-地中海贫血（非脾切除，α-Thal-NS）。从所有患者组中随机选取，36例接受VitE治疗，38例接受安慰剂治疗。在接受VitE的β-Thal-NS患者中，观察到携带PS的RBC和携带PS的RBC囊泡显著减少。这与仅在β-Thal-NS组中发现的脂质过氧化标志物丙二醛水平的大幅下降同时发生，而在β-Thal-S和α-Thal-NS组中未出现这种情况。在β-Thal-NS组中，VitE改善了RBC病理状况，治疗后VitE水平与携带PS的RBC（p = 0.001）以及网织红细胞计数（p = 0.006）呈负相关，尽管Hb水平保持不变。VitE治疗并未改善血小板病理状况或减少MP。VitE组和安慰剂组均未报告不良事件。
每天400 IU的VitE耐受性良好，且与改善TD β-Thal-NS患者的RBC氧化损伤相关。因此，建议对年轻的TD β-Thal-NS患者补充VitE可能有益。
