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红细胞微粒与溶血标志物相关,可能与镰状细胞病患者的临床事件有关。

Red blood cells microparticles are associated with hemolysis markers and may contribute to clinical events among sickle cell disease patients.

机构信息

Hematology and Hemotherapy Center (Hemocentro), University of Campinas (UNICAMP), Rua Carlos Chagas, 480, Barão Geraldo, Campinas, SP, 13083-970, Brazil.

Department of Pediatrics, College of Medicine, Ekiti State University, Ado Ekiti, Nigeria.

出版信息

Ann Hematol. 2019 Nov;98(11):2507-2521. doi: 10.1007/s00277-019-03792-x. Epub 2019 Sep 6.

Abstract

Microparticles are sub-micron vesicles possessing protein and other materials derived from the plasma membrane of their parent cells, and literature suggests that they may have a role in the pathophysiology and downstream manifestations of sickle cell disease (SCD). The contributions of red blood cells microparticles (RMP) to the pathogenic mechanisms and clinical phenotypes of SCD are largely unknown. There is a controversy as to whether the proportions of intravascular hemolysis (approximately ≤ 30% of total hemolysis) would be enough to explain some complications seen in patients with SCD. We investigated RMP among 138 SCD patients and 39 HbAA individuals. Plasma RMPs were quantified by flow cytometry, plasma hemoglobin and heme by colorimetric assays, and haptoglobin and hemopexin by ELISA. The patients had higher RMP, plasma hemoglobin, and heme compared to the controls. On the contrary, haptoglobin and hemopexin were depleted in the patients. The RMP correlated positively with heme, lactate dehydrogenase, plasma hemoglobin, serum bilirubin, reticulocyte counts, and tricuspid regurgitant jet velocity of the patients. Contrarily, it correlated negatively with HbF, hemopexin, red blood cells counts, hemoglobin concentration, and haptoglobin. Although patients treated with hydroxyurea had lower RMP, this did not attain statistical significance. Patients with sickle leg ulcer and elevated tricuspid regurgitant jet velocity had higher levels of RMP. In conclusion, these data suggest that RMPs are associated with hemolysis and may have important roles in the pathophysiology and downstream complications of SCD.

摘要

微粒是亚微米级囊泡,具有来自其母细胞质膜的蛋白质和其他物质,文献表明它们可能在镰状细胞病(SCD)的病理生理学和下游表现中发挥作用。红细胞微粒(RMP)对 SCD 发病机制和临床表型的贡献在很大程度上尚不清楚。关于血管内溶血(约≤30%的总溶血)的比例是否足以解释 SCD 患者的一些并发症存在争议。我们研究了 138 例 SCD 患者和 39 例 HbAA 个体中的 RMP。通过流式细胞术定量检测血浆 RMP,比色法检测血浆血红蛋白和血红素,ELISA 法检测结合珠蛋白和血红素结合蛋白。与对照组相比,患者的 RMP、血浆血红蛋白和血红素水平较高。相反,患者的结合珠蛋白和血红素结合蛋白耗竭。RMP 与患者的血红素、乳酸脱氢酶、血浆血红蛋白、血清胆红素、网织红细胞计数和三尖瓣反流射流速度呈正相关。相反,它与 HbF、血红素结合蛋白、红细胞计数、血红蛋白浓度和结合珠蛋白呈负相关。尽管羟基脲治疗的患者 RMP 较低,但无统计学意义。镰状腿溃疡和三尖瓣反流射流速度升高的患者 RMP 水平较高。总之,这些数据表明 RMP 与溶血有关,可能在 SCD 的病理生理学和下游并发症中发挥重要作用。

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