暴露磷脂酰丝氨酸的血细胞和微颗粒可在非瓣膜性心房颤动中诱导促凝活性。

Phosphatidylserine-exposing blood cells and microparticles induce procoagulant activity in non-valvular atrial fibrillation.

机构信息

Department of Cardiology, The First Hospital, Harbin Medical University, Harbin, China.

出版信息

Int J Cardiol. 2018 May 1;258:138-143. doi: 10.1016/j.ijcard.2018.01.116.

DOI:10.1016/j.ijcard.2018.01.116

PMID:29544920

Abstract

BACKGROUND

The definitive role of phosphatidylserine (PS) in the prothrombotic state of non-valvular atrial fibrillation (NVAF) remains unclear. Our objectives were to study the PS exposure on blood cells and microparticles (MPs) in NVAF, and evaluate their procoagulant activity (PCA).

METHODS

NVAF patients without (n = 60) and with left atrial thrombi (n = 18) and controls (n = 36) were included in our study. Exposed PS was analyzed with flow cytometry and confocal microscopy. PCA was evaluated using clotting time, factor Xa (FXa), thrombin and fibrin formation.

RESULTS

PS blood cells and MPs were significantly higher in NVAF patients without and with left atrial thrombi (both P < 0.01) than in controls. Patients with left atrial thrombi showed increased PS platelets, neutrophils, erythrocytes and MPs compared with patients without thrombi (all P < 0.05). Moreover, in patients with left atrial thrombi, MPs primarily originated from platelets (56.1%) followed by leukocytes (21.9%, including MPs from neutrophils, monocytes and lymphocytes), erythrocytes (12.2%) and endothelial cells (8.9%). Additionally, PS blood cells and MPs contributed to markedly shortened coagulation time and dramatically increased FXa/thrombin/fibrin (all P < 0.001) generation in both NVAF groups. Furthermore, blockade of exposed PS on blood cells and MPs with lactadherin inhibited PCA by approximately 80%. Lastly, we found that the amount of PS platelets and MPs was positively correlated with thrombus diameter (all p < 0.005).

CONCLUSIONS

Our results suggest that exposed PS on blood cells and MPs play a procoagulant role in NVAF patients. Blockade of PS prior to thrombus formation might be a novel therapeutic approach in these patients.

摘要

背景

磷脂酰丝氨酸（PS）在非瓣膜性心房颤动（NVAF）的血栓前状态中的明确作用仍不清楚。我们的目的是研究 NVAF 中血细胞和微颗粒（MPs）上 PS 的暴露情况，并评估其促凝活性（PCA）。

方法

我们纳入了无左心房血栓（n=60）、有左心房血栓（n=18）和对照组（n=36）的 NVAF 患者。用流式细胞术和共聚焦显微镜分析暴露的 PS。用凝血时间、因子 Xa（FXa）、凝血酶和纤维蛋白形成来评估 PCA。

结果

无左心房血栓和有左心房血栓的 NVAF 患者的 PS 血细胞和 MPs 均显著高于对照组（均 P<0.01）。与无血栓患者相比，有左心房血栓的患者 PS 血小板、中性粒细胞、红细胞和 MPs 均显著增加（均 P<0.05）。此外，在有左心房血栓的患者中，MPs 主要来源于血小板（56.1%），其次是白细胞（21.9%，包括来自中性粒细胞、单核细胞和淋巴细胞的 MPs）、红细胞（12.2%）和内皮细胞（8.9%）。此外，PS 血细胞和 MPs 导致凝血时间明显缩短，FXa/凝血酶/纤维蛋白生成显著增加（均 P<0.001），这两种情况均存在于 NVAF 两组中。此外，用乳凝集素阻断血细胞和 MPs 上的暴露 PS 可使 PCA 降低约 80%。最后，我们发现 PS 血小板和 MPs 的数量与血栓直径呈正相关（均 p<0.005）。