COVID-19 patients exhibit reduced procoagulant platelet responses.
COVID-19 patients exhibit reduced procoagulant platelet responses.
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DOI：
10.1111/jth.15107
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Campbell RA
中科院分区：
文献类型：
--
作者：
Denorme F;Manne BK;Portier I;Petrey AC;Middleton EA;Kile BT;Rondina MT;Campbell RA
新出现的证据表明，在COVID-19患者的血栓性并发症中存在血小板反应功能障碍。血小板是炎症诱导血栓形成的重要参与者。特别是，促凝血血小板支持凝血酶生成并介导血栓炎症。检查COVID-19患者的促凝血血小板形成是否改变，以及促凝血血小板是否导致肺血栓形成。从犹他州大学医院系统招募健康供体和COVID-19患者。分离血小板，并通过膜联蛋白V结合测定促凝血血小板形成以及检查线粒体功能。我们利用缺乏形成促凝血血小板（CypDplt−/−）能力的小鼠来研究促凝血血小板在肺血栓形成中的作用。我们观察到，与来自匹配的健康供体的血小板相比，从COVID-19患者中分离的血小板成为促凝血剂的能力降低，这一点可以通过凝血酶和惊厥素双重刺激后线粒体去极化和磷脂酰丝氨酸暴露减少来证明。为了了解体内促凝血血小板反应减少的影响，我们将血小板特异性亲环素D缺失的小鼠（缺乏促凝血血小板形成）置于肺微血管血栓形成模型中。与同窝野生型对照组相比，血小板缺乏亲环素D的小鼠死于肺微血管血栓形成的速度明显更快。这些结果表明，失调的促凝血血小板反应可能有助于血栓性并发症在SARS-CoV-2感染。
Emerging evidence implicates dysfunctional platelet responses in thrombotic complications in COVID-19 patients. Platelets are important players in inflammation-induced thrombosis. In particular, procoagulant platelets support thrombin generation and mediate thromboinflammation. To examine if procoagulant platelets formation is altered in COVID-19 patients and if procoagulant platelets contribute to pulmonary thrombosis. Healthy donors and COVID-19 patients were recruited from the University of Utah Hospital System. Platelets were isolated and procoagulant platelet formation measured by Annexin V binding as well as mitochondrial function were examined. We utilized mice lacking the ability to form procoagulant platelets (CypDplt−/−) to examine the role of procoagulant platelets in pulmonary thrombosis. We observed that platelets isolated from COVID-19 patients had a reduced ability to become procoagulant compared to those from matched healthy donors, as evidenced by reduced mitochondrial depolarization and phosphatidylserine exposure following dual stimulation with thrombin and convulxin. To understand what impact reduced procoagulant platelet responses might have in vivo, we subjected mice with a platelet-specific deletion of cyclophilin D, which are deficient in procoagulant platelet formation, to a model of pulmonary microvascular thrombosis. Mice with platelets lacking cyclophilin D died significantly faster from pulmonary microvascular thrombosis compared to littermate wild-type controls. These results suggest dysregulated procoagulant platelet responses may contribute to thrombotic complications during SARS-CoV-2 infection.
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影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
15.3
作者：
Momi, Stefania;Falcinelli, Emanuela;Gresele, Paolo
通讯作者：
Gresele, Paolo
影响因子：
2
作者：
Calkins, Hugh;Hindricks, Gerhard;Yamane, Teiichi
通讯作者：
Yamane, Teiichi
DOI：
10.1161/01.atv.0000152726.49229.bf
发表时间：
2005-02-01
影响因子：
8.7
作者：
Remenyi, G;Szasz, R;Dale, GL
通讯作者：
Dale, GL
DOI：
10.1161/atvbaha.112.300433
发表时间：
2012-12
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Choo HJ;Saafir TB;Mkumba L;Wagner MB;Jobe SM
通讯作者：
Jobe SM