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J Crit Care
. 2023 Nov 15:79:154463.
doi: 10.1016/j.jcrc.2023.154463. Online ahead of print. Presence of procoagulant peripheral blood mononuclear cells in severe COVID-19 patients relate to ventilation perfusion mismatch and precede pulmonary embolism
M Raadsen 1 , T Langerak 1 , J Du Toit 2 , M J H A Kruip 3 , D Aynekulu Mersha 4 , M de Maat 3 , B Vermin 5 , J P C Van den Akker 6 , K S Schmitz 1 , K Bakthiari 7 , J C Meijers 7 , E C M van Gorp 1 , K R Short 8 , B Haagmans 1 , R D de Vries 1 , D A M P J Gommers 6 , H Endeman 6 , M Goeijenbier 9 ; Dutch COVID & Thrombosis Coalition
Affiliations
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.
Keywords: COVID-19; Immunothrombosis; Pulmonary embolism; SARS-CoV-2; Tissue factor.
. 2023 Nov 15:79:154463.
doi: 10.1016/j.jcrc.2023.154463. Online ahead of print. Presence of procoagulant peripheral blood mononuclear cells in severe COVID-19 patients relate to ventilation perfusion mismatch and precede pulmonary embolism
M Raadsen 1 , T Langerak 1 , J Du Toit 2 , M J H A Kruip 3 , D Aynekulu Mersha 4 , M de Maat 3 , B Vermin 5 , J P C Van den Akker 6 , K S Schmitz 1 , K Bakthiari 7 , J C Meijers 7 , E C M van Gorp 1 , K R Short 8 , B Haagmans 1 , R D de Vries 1 , D A M P J Gommers 6 , H Endeman 6 , M Goeijenbier 9 ; Dutch COVID & Thrombosis Coalition
Affiliations
- PMID: 37976997
- DOI: 10.1016/j.jcrc.2023.154463
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.
Keywords: COVID-19; Immunothrombosis; Pulmonary embolism; SARS-CoV-2; Tissue factor.