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Publications

Journal Article Ahead of print

PubMed: 42224841 DOI: 10.1016/j.thromres.2026.109723

Inhibition of inflammation reduces hypofibrinolysis in severe COVID-19: A nested case-control study within the MaastrICCht cohort.

Thromb Res 262:109723

Authors: Joep Schellens, Magdolna Nagy, Anne-Marije Hulshof, Frank van Rosmalen, René van Oerle, Thijs T W van Herpt, Teba Alnima, Mark M G Mulder, Dave Hellenbrand, Hugo Ten Cate, Rob G H Driessen, Jan-Willem E M Sels, Iwan C C van der Horst, Yvonne M C Henskens, Bas C T van Bussel, Henri M H Spronk

Affiliations

  • Department of Intensive Care Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
  • Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Thrombosis Expertise Center, Heart & Vascular Center, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
  • Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Central Diagnostic Laboratory, Maastricht University Medical Centre+, Maastricht, the Netherlands.
  • Department of Intensive Care Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
  • Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, Netherlands.
  • Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Department of Anesthesiology, Maastricht University Medical Centre+, Maastricht, the Netherlands.
  • Central Diagnostic Laboratory, Maastricht University Medical Centre+, Maastricht, the Netherlands.
  • Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Thrombosis Expertise Center, Heart & Vascular Center, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands.
  • Department of Intensive Care Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Department of Cardiology, Maastricht University Medical Centre+, Maastricht, the Netherlands.
  • Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Board of Directors, Albert Schweitzer Hospital, Dordrecht, the Netherlands.
  • Department of Intensive Care Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands.
  • Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Thrombosis Expertise Center, Heart & Vascular Center, Maastricht University Medical Center+, Maastricht, the Netherlands; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, Netherlands.

Abstract

BACKGROUND

Critically ill COVID-19 patients exhibit a hypercoagulable and hypofibrinolytic phenotype, further characterized by a prolonged clotting time in rotational thromboelastometry (ROTEM) measurements. We investigated the effects of immunosuppressants on measures of coagulability and fibrinolysis in these patients.

PATIENTS/METHODS

In a nested case-control study within the Maastricht Intensive Care COVID cohort (MaastrICCht), three patient groups were age and sex matched: dexamethasone, dexamethasone and tocilizumab, and no anti-inflammatory treatment. Clotting time (CT) was assessed using the ROTEM EXTEM assay. Lysis onset time (LOT) and duration (lysis time (LT)) were assessed using tissue plasminogen activated (tPA)-ROTEM. Biomarkers of inflammation, coagulation, and fibrinolysis were also measured. Linear mixed-effect models compared trajectories of these markers between groups.

RESULTS

Out of the full cohort of 324 patients, 36 patients (12 per group) were matched. CT-EXTEM was 23 s 95% CI [-52;5] shorter in dexamethasone and 36 s [-65;-7] shorter in tocilizumab versus no anti-inflammatory treatment group. LT appeared lowest in the week after administering tocilizumab, which effect became less clear over the next two weeks. Compared to no anti-inflammatory treatment, CRP was 235 mg/L 95% CI [-334;-137] lower in the dexamethasone and 318 mg/L [-416;-220] lower in the tocilizumab group, with diminishing effects over time. Plasminogen activator inhibitor 1 (PAI-1) was 3.2 ng/mL [-9.9;3.6] lower in the dexamethasone group and 9.3 ng/mL [-16.2;-2.4] lower in the tocilizumab group, which appeared lowest the week after administering tocilizumab and increased over the next two weeks.

CONCLUSIONS

In critically ill COVID-19 patients, anti-inflammatory treatment, particularly tocilizumab, is associated with reduced PAI-1 levels and accelerated clot lysis, indicating alleviated fibrinolysis.

MeSH

Plasminogen Activator Inhibitor 1, Hemorrhage, Fibrinolysis, Dexamethasone, Case-Control Studies, Covid-19, Therapeutics, Thrombosis, Hemostasis