Department of Cardiology of the First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, China.
Department of Cardiology of the Second Hospital, Harbin Medical University, Harbin, China.
J Thromb Thrombolysis. 2019 Aug;48(2):187-194. doi: 10.1007/s11239-019-01889-8.
Relatively little information is known about the definitive role of phosphatidylserine (PS) in the hypercoagulability of heart failure (HF). Our objectives were to assess the levels of PS exposure on microparticles (MPs) and blood cells (BCs) in each group of HF patients and to evaluate their procoagulant activity (PCA). HF patients in each NYHA functional class II-IV (II n = 30, III n = 30, IV n = 30) and healthy controls (n = 25) were enrolled in the present study. PS exposure on MPs, BCs was analyzed with flow cytometry. MPs were classified based on their cellular origin: platelets (CD41a), neutrophils (CD66b), endothelial cells (CD31CD41a), erythrocytes (CD235a), monocytes (CD14), T lymphocytes (CD3), and B lymphocytes (CD19). PCA was evaluated by clotting time, extrinsic/intrinsic FXa and prothrombinase production assays, as well as fibrin formation assays. Inhibition assays of PCA of PS BCs and MPs were performed by lactadherin. There was no significant difference in MP cellular origin between healthy and HF subjects. However, the total number of PS MPs was significantly increased in HF patients compared with healthy controls. In addition, circulating PS BCs cooperated with PS MPs to markedly shorten coagulation time and dramatically increase FXa/thrombin generation and fibrin formation in each HF group. Moreover, blockade of exposed PS on BCs and MPs with lactadherin inhibited PCA by approximately 80%. Our results lead us to believe that exposing PS on the injured BCs and MPs played a pivotal role in the hypercoagulability state in HF patients.
关于磷脂酰丝氨酸（PS）在心力衰竭（HF）高凝状态中的明确作用，人们知之甚少。我们的目的是评估 HF 患者各组中 PS 在微粒（MPs）和血细胞（BCs）上的暴露水平，并评估其促凝活性（PCA）。本研究纳入了每个 NYHA 功能分类 II-IV 级（II 组 n=30、III 组 n=30、IV 组 n=30）的 HF 患者和健康对照者（n=25）。使用流式细胞术分析 MPs 和 BCs 上的 PS 暴露。根据其细胞来源对 MPs 进行分类：血小板（CD41a）、中性粒细胞（CD66b）、内皮细胞（CD31CD41a）、红细胞（CD235a）、单核细胞（CD14）、T 淋巴细胞（CD3）和 B 淋巴细胞（CD19）。通过凝固时间、外源性/内源性 FXa 和凝血酶原酶生成测定以及纤维蛋白形成测定评估 PCA。通过乳酰脱氢酶抑制 PS BCs 和 MPs 的 PCA。健康和 HF 患者之间 MP 的细胞来源没有显著差异。然而，与健康对照组相比，HF 患者的总 PS MPs 数量显著增加。此外，循环 PS BCs 与 PS MPs 共同作用，显著缩短凝血时间，并在每个 HF 组中显著增加 FXa/凝血酶生成和纤维蛋白形成。此外，用乳酰脱氢酶阻断 BCs 和 MPs 上暴露的 PS 可抑制 PCA 约 80%。我们的研究结果表明，受损的 BCs 和 MPs 上 PS 的暴露在 HF 患者的高凝状态中起着关键作用。
