High plasma levels of Activated Factor VII-Antithrombin Complex Point to increased Tissue Factor Expression in patients with SARS-CoV-2 pneumonia: a potential link with COVID-19 Prothrombotic Diathesis
Martinelli N, Rigoni AM, De Marchi S, Osti N, Donini M, Montagnana M, Castagna A, Pattini P, Udali S, De Franceschi L, Tinazzi E, Mazzi F, Moruzzi S, Argentino G, Delfino L, Sartori G, Azzini AM, Tacconelli E, Van Dreden P, Lippi G, Girelli D, Olivieri O, Friso S, Pizzolo F
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19), in which coagulation abnormalities and endothelial dysfunction play a key pathogenic role. Tissue factor (TF) expression is triggered by endothelial dysfunction. Activated factor VII-antithrombin (FVIIa-AT) complex reflects indirectly FVIIa-TF interaction and has been proposed as a potential biomarker of prothrombotic diathesis. FVIIa-AT plasma concentration was measured in 40 patients (30 males and 10 females; 64.8 ± 12.3 years) admitted with SARS-CoV-2 pneumonia during the first pandemic wave in Italy. Two sex- and age-matched cohorts without COVID-19, with or without signs of systemic inflammation, were used to compare FVIIa-AT data. The FVIIa-AT plasma levels in COVID-19 patients were higher than those in non-COVID-19 subjects, either with or without inflammation, while no difference was observed among non-COVID-19 subjects. The association between COVID-19 and FVIIa-AT levels remained significant after adjustment for sex, age, C-reactive protein, renal function, fibrinogen, prothrombin time and activated partial thromboplastin time. Our results indicate that SARS-CoV-2 infection, at least during the first pandemic wave, was characterized by high FVIIa-AT levels, which may suggest an enhanced FVIIa-TF interaction in COVID-19, potentially consistent with SARS-CoV-2-induced endotheliopathy.
Keywords: activated factor VII-antithrombin (FVIIa-AT); coagulation; coronavirus disease 2019 (COVID-19); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); tissue factor (TF).