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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. © 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Citation

Shuting Ji, Weijun Dong, Yushan Qi, Hong Gao, Danwei Zhao, Minghui Xu, Tingting Li, Hongyin Yu, Yuting Sun, Ruishuang Ma, Jialan Shi, Chunyan Gao. Phagocytosis by endothelial cells inhibits procoagulant activity of platelets of essential thrombocythemia in vitro. Journal of thrombosis and haemostasis : JTH. 2020 Jan;18(1):222-233

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PMID: 31442368

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