期刊
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
卷 19, 期 9, 页码 2193-2198出版社
ELSEVIER SCIENCE INC
DOI: 10.1111/jth.15445
关键词
ADAMTS13; ADAMTS13 conformation; COVID-19; thrombotic microangiopathy; von Willebrand factor
资金
- KU Leuven
Clinical features, hemostatic laboratory parameters, VWF/ADAMTS13 axis, and ADAMTS13 conformation were investigated in critically ill COVID-19 patients at admission. The study found that an imbalance between high VWF antigen levels and normal or slightly decreased ADAMTS13 activity levels correlated with mortality, suggesting that these markers may reflect inflammation and endothelial damage rather than driving the thrombotic process of COVID-19.
Background Critically ill patients with coronavirus disease 2019 (COVID-19) are prone to developing macrothrombosis and microthrombosis. COVID-19 has been reported to be rarely associated with thrombotic microangiopathies. A disintegrin and metalloprotease with thrombospondin type I repeats, member 13 (ADAMTS13) severe deficiency, the hallmark of thrombotic thrombocytopenic purpura (TTP), induces the formation of platelet, unusually large von Willebrand factor (VWF) multimer microthrombi. In immune-mediated TTP, ADAMTS13 adopts specifically an open conformation. The VWF/ADAMTS13 couple may contribute to the microthrombi formation in pulmonary alveolar capillaries in COVID-19. Objective To investigate clinical features, hemostatic laboratory parameters, VWF/ADAMTS13 axis, and ADAMTS13 conformation in critically ill COVID-19 patients at admission. Methods Fifty three critically ill COVID-19 patients were enrolled between March 18 and May 9 2020 in a monocentric hospital. Results The median age was 59 years and the male-to-female ratio was 2.8/1. We reported seven pulmonary embolisms and 15 deaths. Biological investigations showed increased fibrinogen and factor V levels, and strongly increased D-dimers correlated with mortality. No patient presented severe thrombocytopenia nor microangiopathic hemolytic anemia. An imbalance between high VWF antigen levels and normal or slightly decreased ADAMTS13 activity levels (strongly elevated VWF/ADAMTS13 ratio) was correlated with mortality. Three patients had a partial quantitative deficiency in ADAMTS13. We also reported a closed conformation of ADAMTS13 in all patients, reinforcing the specificity of an open conformation of ADAMTS13 as a hallmark of TTP. Conclusion We suggest that slightly decreased or normal ADAMTS13 activity and highly elevated VWF are rather biomarkers reflecting both the strong inflammation and the endothelial damage rather than drivers of the thrombotic process of COVID-19.
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