Department of Plasma Proteins, Sanquin, Amsterdam, The Netherlands.
Department of Hematology, Erasmus MC, Cancer Institute, Rotterdam, The Netherlands.
Blood Adv. 2020 Jul 14;4(13):2967-2978. doi: 10.1182/bloodadvances.2020001640.
Thrombocytopenia is a common complication of influenza virus infection, and its severity predicts the clinical outcome of critically ill patients. The underlying cause(s) remain incompletely understood. In this study, in patients with an influenza A/H1N1 virus infection, viral load and platelet count correlated inversely during the acute infection phase. We confirmed this finding in a ferret model of influenza virus infection. In these animals, platelet count decreased with the degree of virus pathogenicity varying from 0% in animals infected with the influenza A/H3N2 virus, to 22% in those with the pandemic influenza A/H1N1 virus, up to 62% in animals with a highly pathogenic A/H5N1 virus infection. This thrombocytopenia is associated with virus-containing platelets that circulate in the blood. Uptake of influenza virus particles by platelets requires binding to sialoglycans and results in the removal of sialic acids by the virus neuraminidase, a trigger for hepatic clearance of platelets. We propose the clearance of influenza virus by platelets as a paradigm. These insights clarify the pathophysiology of influenza virus infection and show how severe respiratory infections, including COVID-19, may propagate thrombocytopenia and/or thromboembolic complications.
血小板减少症是流感病毒感染的常见并发症，其严重程度可预测危重症患者的临床结局。但其潜在原因尚不完全清楚。在这项研究中，在甲型 H1N1 流感病毒感染患者中，病毒载量和血小板计数在急性感染期呈负相关。我们在流感病毒感染的雪貂模型中证实了这一发现。在这些动物中，血小板计数随病毒致病性的变化而变化，从感染甲型 H3N2 病毒的动物中减少 0%，到感染大流行的甲型 H1N1 病毒的动物中减少 22%，再到感染高致病性甲型 H5N1 病毒的动物中减少 62%。这种血小板减少症与在血液中循环的含有病毒的血小板有关。血小板对流感病毒颗粒的摄取需要与唾液酸糖结合，导致病毒神经氨酸酶去除唾液酸，这是血小板被肝脏清除的触发因素。我们提出血小板清除流感病毒作为一个范例。这些见解阐明了流感病毒感染的病理生理学，并表明包括 COVID-19 在内的严重呼吸道感染如何导致血小板减少症和/或血栓栓塞并发症的发生。
