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.
- Wygrecka, M.
- Birnhuber, A.
- Seeliger, B.
- Michalick, L.
- Pak, O.
- Schultz, A. S.
- Schramm, F.
- Zacharias, M.
- Gorkiewicz, G.
- David, S.
- Welte, T.
- Schmidt, J. J.
- Weissmann, N.
- Schermuly, R. T.
- Barreto, G.
- Schaefer, L.
- Markart, P.
- Brack, M. C.
- Hippenstiel, S.
- Kurth, F.
- Sander, L.
- Witzenrath, M.
- Kuebler, W.
- Kwapiszewska, G.
- Preissner, K. T.
