Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19.
Fiche publication
Date publication
décembre 2021
Journal
Blood advances
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BARRETO Guillermo
Tous les auteurs :
Wygrecka M, Birnhuber A, Seeliger B, Michalick L, Pak O, Schultz AS, Schramm F, Zacharias M, Gorkiewicz G, David S, Welte T, Schmidt JJ, Weissmann N, Schermuly RT, Barreto G, Schaefer L, Markart P, Brack MC, Hippenstiel S, Kurth F, Sander L, Witzenrath M, Kuebler W, Kwapiszewska G, Preissner KT
Lien Pubmed
Résumé
The high incidence of thrombotic events suggests a possible role of the contact system pathway in COVID-19 pathology. Here, we demonstrate altered levels of factor XII (FXII) and its activation products in critically ill COVID-19 patients in comparison to patients with severe acute respiratory distress syndrome due to influenza virus (ARDS-influenza). Compatible with this data, we report rapid consumption of FXII in COVID-19, but not in ARDS-influenza, plasma. Interestingly, the lag phase in fibrin formation, triggered by the FXII activator kaolin, was not prolonged in COVID-19 as opposed to ARDS-influenza. Using confocal and electron microscopy, we showed that increased FXII activation rate, in conjunction with elevated fibrinogen levels, triggers formation of fibrinolysis-resistant, compact clots with thin fibers and small pores in COVID-19. Accordingly, clot lysis was markedly impaired in COVID-19 as opposed to ARDS-infleunza subjects. Dysregulatated fibrinolytic system, as evidenced by elevated levels of thrombin-activatable fibrinolysis inhibitor, tissue-plasminogen activator, and plasminogen activator inhibitor-1 in COVID-19 potentiated this effect. Analysis of lung tissue sections revealed wide-spread extra- and intra-vascular compact fibrin deposits in COVID-19 patients. Together, compact fibrin network structure and dysregulated fibrinolysis may collectively contribute to high incidence of thrombotic events in COVID-19.
Référence
Blood Adv. 2021 Dec 3;: