An important component of severe COVID-19 disease is virus-induced endothelilitis. This leads to disruption of normal endothelial function, initiating a state of failing normal clotting physiology. Massively increased levels of von Willebrand Factor (VWF) lead to overwhelming platelet activation, as well as activation of the enzymatic (intrinsic) clotting pathway. In addition, there is an impaired fibrinolysis, caused by, amongst others, increased levels of alpha-(2) antiplasmin. The end result is hypercoagulation [proven by thromboelastography^® (TEG^®)] and reduced fibrinolysis, inevitably leading to a difficult-to-overcome hypercoagulated physiological state. Platelets in circulation also plays a significant role in clot formation, but themselves may also drive hypercoagulation when they are overactivated due to the interactions of their receptors with the endothelium, immune cells or circulating inflammatory molecules. From the literature it is clear that the role of platelets in severely ill COVID-19 patients has been markedly underestimated or even ignored. We here highlight the value of early management of severe COVID-19 coagulopathy as guided by TEG^®, microclot and platelet mapping. We also argue that the failure of clinical trials, where the efficacy of prophylactic versus therapeutic clexane (low molecular weight heparin (LMWH)) were not always successful, might be because the significant role of platelet activation was not taken into account during the planning of the trial. We conclude that, because of the overwhelming alteration of clotting, the outcome of any trial evaluating an any single anticoagulant, including thrombolytic, would be negative. Here we suggest the use of the degree of platelet dysfunction and presence of microclots in circulation, together with TEG^®, should be used as a guideline for disease severity. A multi-pronged approach, guided by TEG^® and platelet mapping, would be required to maintain normal clotting physiology in severe COVID-19 disease.

中文翻译：

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严重 COVID-19 凝血病的早期管理应以 TEG®、微凝块和血小板作图为指导

严重的 COVID-19 疾病的一个重要组成部分是病毒引起的内皮炎。这会导致正常内皮功能的破坏，启动正常凝血生理机能失败的状态。血管性血友病因子 (VWF) 水平的大量增加导致压倒性的血小板激活，以及酶促（内在）凝血途径的激活。此外，由于 α-(2) 抗纤溶酶水平升高，纤维蛋白溶解受损。最终结果是高凝状态 [通过血栓弹力图^® (TEG ^®)] 和纤维蛋白溶解减少，不可避免地导致难以克服的高凝生理状态。循环中的血小板在凝块形成中也起着重要作用，但当它们的受体与内皮、免疫细胞或循环炎症分子的相互作用过度激活时，它们本身也可能驱动高凝状态。从文献中可以清楚地看出，血小板在重症 COVID-19 患者中的作用被明显低估甚至被忽视。我们在此强调在 TEG ^®指导下早期管理严重 COVID-19 凝血病的价值、微凝块和血小板作图。我们还争辩说，临床试验的失败，其中预防性与治疗性 Clexane（低分子量肝素（LMWH））的疗效并不总是成功，可能是因为在规划过程中没有考虑血小板活化的重要作用。试用。我们得出的结论是，由于凝血的巨大改变，任何评估任何单一抗凝剂（包括溶栓剂）的试验的结果都是阴性的。在这里，我们建议将血小板功能障碍的程度和循环中微凝块的存在与 TEG ^®一起用作疾病严重程度的指南。多管齐下的方法，由 TEG ^®指导 和血小板作图，在严重的 COVID-19 疾病中需要维持正常的凝血生理机能。