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Altered Fibrin Network Structure and Fibrinolysis in Intensive Care Unit Patients with COVID-19, Not Entirely Explaining the Increased Risk of Thrombosis

1Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands, Rotterdam, Zuid-Holland, Netherlands, 2Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands, Rotterdam, Zuid-Holland, Netherlands, 3Optical Imaging Center, Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Zuid-Holland, Netherlands, 4University Medical Center Utrecht, Utrecht, Utrecht, Netherlands, 5UMC Utrecht, Utrecht, Utrecht, Netherlands, 6Department of Medical Microbiology and Infectious Diseases & Department of Internal Medicine, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands, Rotterdam, Zuid-Holland, Netherlands, 7Department of Pulmonary Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands, Rotterdam, Zuid-Holland, Netherlands, 8Department of Internal Medicine & Department of Viroscience, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands, Rotterdam, Zuid-Holland, Netherlands, 9Department of Viroscience & Department of Adult Intensive Care, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands, Rotterdam, Zuid-Holland, Netherlands, 10Department of Adult Intensive Care, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands, Rotterdam, Zuid-Holland, Netherlands, 11Erasmus University Medical Center, Rotterdam, The Netherlands, Rotterdam, Zuid-Holland, Netherlands

Abstract Number: PB0592

Meeting: ISTH 2022 Congress

Theme: COVID and Coagulation » COVID and Coagulation, Basic Science

Background: SARS-CoV-2 infection is associated with an increased incidence of thrombosis.

Aims: By studying the fibrin network structure of COVID-19 patients, we aimed to unravel pathophysiological mechanisms that contribute to this increased risk of thrombosis. This may contribute to optimal prevention and treatment of COVID-19 related thrombosis.

Methods: In this case-control study, we collected plasma samples from intensive care unit (ICU) patients with COVID-19, with and without confirmed thrombosis, between April and December 2020. Additionally, we collected plasma from COVID-19 patients admitted to general wards without thrombosis, from ICU patients with pneumococcal infection, and from healthy controls. Fibrin fiber diameters and fibrin network density were quantified in plasma clots imaged with stimulated emission depletion (STED) microscopy and confocal microscopy. Finally, we determined the sensitivity to fibrinolysis. Ethical approval was obtained and written informed consent was obtained or an opt-out procedure was in place.

Results: COVID-19 ICU patients (n=37) and ICU patients with pneumococcal disease (n=7) showed significantly higher fibrin network densities and longer plasma clot lysis times than healthy controls (n=7) (Figure 1). No differences were observed between COVID-19 ICU patients with and without thrombosis, or ICU patients with pneumococcal infection. At a second time point, after thrombosis or at a similar time point in patients without thrombosis, we observed thicker fibers and longer lysis times in COVID-19 ICU patients with thrombosis (n=19) than in COVID-19 ICU patients without thrombosis (n=18).

Conclusion(s): Our results suggest that severe COVID-19 is associated with a changed fibrin network structure and decreased susceptibility to fibrinolysis. Since these changes were not exclusive to COVID-19 patients, they may not explain the increased thrombosis risk.

Image

Figure 1. Characteristics of clots formed from plasma collected at the first time point -before the diagnosis of thrombosis in case of COVID-19 ICU patients with thrombosis-. COVID-19 ICU – means patients without confirmed thrombosis, COVID-19 ICU + means patients with confirmed thrombosis. One-way ANOVA or Kruskal Wallis test with Tukey’s post-hoc tests. *p < 0.05; **p < 0.01; ***p < 0.001.

To cite this abstract in AMA style:

de Vries J, Visser C, Geers L, Slotman J, van Kleef N, Maas C, Bax H, Miedema J, van Gorp E, Goeijenbier M, van den Akker J, Endeman H, Rijken D, Kruip M, de Maat M. Altered Fibrin Network Structure and Fibrinolysis in Intensive Care Unit Patients with COVID-19, Not Entirely Explaining the Increased Risk of Thrombosis [abstract]. https://abstracts.isth.org/abstract/altered-fibrin-network-structure-and-fibrinolysis-in-intensive-care-unit-patients-with-covid-19-not-entirely-explaining-the-increased-risk-of-thrombosis/. Accessed September 29, 2023.

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