Presence of procoagulant peripheral blood mononuclear cells in severe COVID-19 patients relate to ventilation perfusion mismatch and precede pulmonary embolism

Dutch Covid-19 and Thrombosis Coalition (DCTC), M. Raadsen, T. Langerak, J. Du Toit, M. J.H.A. Kruip, D. Aynekulu Mersha, M. P.M. De Maat, B. Vermin, J. P.C. Van den Akker, K. S. Schmitz, K. Bakhtiari, J. C.M. Meijers, E. C.M. van Gorp, K. R. Short, B. Haagmans, R. D. de Vries, D. A.M.P.J. Gommers, H. Endeman, M. Goeijenbier*

*Corresponding author for this work

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Abstract

PURPOSE: Pulmonary emboli (PE) contribute substantially to coronavirus disease 2019 (COVID-19) related mortality and morbidity. Immune cell-mediated hyperinflammation drives the procoagulant state in COVID-19 patients, resulting in immunothrombosis. To study the role of peripheral blood mononuclear cells (PBMC) in the procoagulant state of COVID-19 patients, we performed a functional bioassay and related outcomes to the occurrence of PE. Secondary aims were to relate this functional assay to plasma D-dimer levels, ventilation perfusion mismatch and TF expression on monocyte subsets. METHODS: PBMC from an ICU biobank were obtained from 20 patients with a computed tomography angiograph (CTA) proven PE and compared to 15 COVID-19 controls without a proven PE. Functional procoagulant properties of PBMC were measured using a modified fibrin generation time (MC-FGT) assay. Tissue factor (TF) expression on monocyte subsets were measured by flow cytometry. Additional clinical data were obtained from patient records including end-tidal to arterial carbon dioxide gradient. RESULTS: MC-FGT levels were highest in the samples taken closest to the PE detection, similar to the end-tidal to arterial carbon dioxide gradient (ETCO2 - PaCO2), a measurement to quantify ventilation-perfusion mismatch. In patients without proven PE, peak MC-FGT relates to an increase in end-tidal to arterial carbon dioxide gradient. We identified non-classical, CD16 positive monocytes as the subset with increased TF expression. CONCLUSION: We show that the procoagulant state of PBMC could aid in early detection of PE in COVID-19 ICU patients. Combined with end-tidal to ETCO2 - PaCO2 gradient, these tests could improve early detection of PE on the ICU.

Original languageEnglish
Article number154463
JournalJournal of Critical Care
Volume79
DOIs
Publication statusPublished - 1 Feb 2024

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