Department of Medical Laboratory Science and Technology, Harbin Medical University-Daqing, Daqing, China.
Department of General Surgery, The Fifth Hospital, Harbin Medical University, Daqing, China.
J Thromb Haemost. 2020 Jan;18(1):222-233. doi: 10.1111/jth.14617. Epub 2019 Sep 10.
Essential thrombocythemia (ET) is characterized by thrombocytosis with increased platelet number and persistent activation. The mechanisms of thrombosis and the fate of these platelets are not clear. The aim of the present study is to explore the phagocytosis of platelets of ET patients by endothelial cells (ECs) in vitro and its relevance to the procoagulant activity (PCA).
Phosphatidylserine (PS) exposure on platelets was detected by flow cytometry. Phagocytosis of the platelets by ECs was performed using flow cytometry, confocal microscopy, and electron microscopy. The PCA of platelets was evaluated by coagulation time and purified coagulation complex assays.
The PS exposure on platelets in ET patients is higher than that in healthy controls. The PS-exposed platelets are highly procoagulant and lactadherin reduced 80% of the PCA by blockade of PS. When cocultured, the platelets of ET patients were sequestered by ECs in a time-dependent fashion. Lactadherin enhanced phagocytosis by bridging the PS on activated platelets and the integrin αvβ3 on ECs, and P-selectin played at least a partial role in this process. Furthermore, factor Xa and prothrombinase activity of PS-exposed platelets were decreased after incubation with ECs.
Our results suggest that phagocytic clearance of platelets by ECs occurs in ET patients, thus representing a novel mechanism to remove activated platelets from the circulation; lactadherin and phagocytosis could cooperatively limit the thrombophilia in ET patients.
特发性血小板增多症（ET）的特征是血小板计数增加伴血小板持续活化。血栓形成的机制和这些血小板的命运尚不清楚。本研究旨在探讨 ET 患者血小板在体外被内皮细胞（ECs）吞噬的情况及其与促凝活性（PCA）的相关性。
采用流式细胞术检测血小板上的磷脂酰丝氨酸（PS）暴露。通过流式细胞术、共聚焦显微镜和电子显微镜检测 ECs 对血小板的吞噬作用。通过凝血时间和纯化凝血复合物测定评估血小板 PCA。
ET 患者血小板上 PS 的暴露高于健康对照组。PS 暴露的血小板具有高度促凝活性，而 lactadherin 通过阻断 PS 减少了 80%的 PCA。共培养时，ET 患者的血小板以时间依赖性方式被 ECs 隔离。Lactadherin 通过桥接活化血小板上的 PS 和 ECs 上的整合素 αvβ3 增强吞噬作用，而 P-选择素在这个过程中至少发挥了部分作用。此外，PS 暴露的血小板与 ECs 孵育后，其 Xa 因子和凝血酶原酶活性降低。
我们的结果表明，ECs 对血小板的吞噬清除作用发生在 ET 患者中，这代表了一种从循环中清除活化血小板的新机制；lactadherin 和吞噬作用可以协同限制 ET 患者的血栓形成倾向。
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