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.
BACKGROUND:Critically illpatients 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 illCOVID-19patients at admission. METHODS: Fifty three critically illCOVID-19patients 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.
Authors: Denise Battaglini; Miquéias Lopes-Pacheco; Hugo C Castro-Faria-Neto; Paolo Pelosi; Patricia R M Rocco Journal: Front Immunol Date: 2022-04-27 Impact factor: 8.786
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Authors: Kiruphagaran Thangaraju; Upendra Katneni; Imo J Akpan; Kenichi Tanaka; Tiffany Thomas; Saini Setua; Julie A Reisz; Francesca Cendali; Fabia Gamboni; Travis Nemkov; Stacie Kahn; Alexander Z Wei; Jacob E Valk; Krystalyn E Hudson; David J Roh; Chiara Moriconi; James C Zimring; Angelo D'Alessandro; Steven L Spitalnik; Richard O Francis; Paul W Buehler Journal: Front Med (Lausanne) Date: 2022-01-10
Authors: György Sinkovits; Marienn Réti; Veronika Müller; Zsolt Iványi; János Gál; László Gopcsa; Péter Reményi; Beáta Szathmáry; Botond Lakatos; János Szlávik; Ilona Bobek; Zita Z Prohászka; Zsolt Förhécz; Blanka Mező; Dorottya Csuka; Lisa Hurler; Erika Kajdácsi; László Cervenak; Petra Kiszel; Tamás Masszi; István Vályi-Nagy; Zoltán Prohászka Journal: Thromb Haemost Date: 2022-01-21 Impact factor: 5.249