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

被引:2
作者
Raadsen, M. [1 ]
Langerak, T. [1 ]
Du Toit, J. [1 ,2 ]
Kruip, M. J. H. A. [3 ]
Mersha, D. Aynekulu [1 ,5 ]
De Maat, M. P. M. [3 ]
Vermin, B. [4 ]
Van den Akker, J. P. C. [5 ]
Schmitz, K. S. [1 ]
Bakhtiari, K. [6 ]
Meijers, J. C. M. [6 ]
van Gorp, E. C. M. [1 ]
Short, K. R. [7 ]
Haagmans, B. [1 ]
de Vries, R. D. [1 ]
Gommers, D. A. M. P. J. [5 ]
Endeman, H. [5 ]
Goeijenbier, M. [4 ,5 ]
机构
[1] Erasmus MC, Dept Virosci, Rotterdam, Netherlands
[2] Wits Donal Gordon Med Ctr, Dept Hematol, Johannesburg, South Africa
[3] Erasmus MC, Dept Hematol, Rotterdam, Netherlands
[4] Spaarne Gasthuis, Dept Intens Care, Hoofddorp, Netherlands
[5] Erasmus MC, Dept Intens Care, Rotterdam, Netherlands
[6] Sanquin Res, Dept Mol Hematol, Amsterdam, Netherlands
[7] Univ Queensland, Sch Chem & Mol Biosci, St Lucia, Australia
关键词
COVID-19; SARS-CoV-2; Immunothrombosis; Pulmonary embolism; Tissue factor;
D O I
10.1016/j.jcrc.2023.154463
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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.
引用
收藏
页数:8
相关论文
共 18 条
[11]   D-dimer level in COVID-19 infection: a systematic review [J].
Rostami, Mehrdad ;
Mansouritorghabeh, Hassan .
EXPERT REVIEW OF HEMATOLOGY, 2020, 13 (11) :1265-1275
[12]   Heterogeneity of Ventilation/Perfusion Mismatch at Different Levels of PEEP and in Mechanical Phenotypes of COVID-19 ARDS [J].
Scaramuzzo, Gaetano ;
Karbing, Dan Stieper ;
Fogagnolo, Alberto ;
Mauri, Tommaso ;
Spinelli, Elena ;
Mari, Matilde ;
Turrini, Cecilia ;
Montanaro, Federica ;
Volta, Carlo Alberto ;
Rees, Stephen Edward ;
Spadaro, Savino .
RESPIRATORY CARE, 2023, 68 (02) :188-198
[13]   Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis [J].
Skendros, Panagiotis ;
Mitsios, Alexandros ;
Chrysanthopoulou, Akrivi ;
Mastellos, Dimitrios C. ;
Metallidis, Simeon ;
Rafailidis, Petros ;
Ntinopoulou, Maria ;
Sertaridou, Eleni ;
Tsironidou, Victoria ;
Tsigalou, Christina ;
Tektonidou, Maria ;
Konstantinidis, Theocharis ;
Papagoras, Charalampos ;
Mitroulis, Ioannis ;
Germanidis, Georgios ;
Lambris, John D. ;
Ritis, Konstantinos .
JOURNAL OF CLINICAL INVESTIGATION, 2020, 130 (11) :6151-6157
[14]   Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19 The HEP-COVID Randomized Clinical Trial [J].
Spyropoulos, Alex C. ;
Goldin, Mark ;
Giannis, Dimitrios ;
Diab, Wassim ;
Wang, Janice ;
Khanijo, Sameer ;
Mignatti, Andrea ;
Gianos, Eugenia ;
Cohen, Marc ;
Sharifova, Gulru ;
Lund, Jeet M. ;
Tafur, Alfonso ;
Lewis, Paul A. ;
Cohoon, Kevin P. ;
Rahman, Husneara ;
Sison, Cristina P. ;
Lesser, Martin L. ;
Ochani, Kanta ;
Agrawal, Nirav ;
Hsia, Judith ;
Anderson, Victoria E. ;
Bonaca, Marc ;
Halperin, Jonathan L. ;
Weitz, Jeffrey, I .
JAMA INTERNAL MEDICINE, 2021, 181 (12) :1612-1620
[15]   Tissue factor in COVID-19-associated coagulopathy [J].
Subramaniam, Saravanan ;
Kothari, Hema ;
Bosmann, Markus .
THROMBOSIS RESEARCH, 2022, 220 :35-47
[16]   Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study [J].
van der Hulle, Tom ;
Cheung, Whitney Y. ;
Kooij, Stephanie ;
Beenen, Ludo F. M. ;
van Bemmel, Thomas ;
van Es, Josien ;
Faber, Laura M. ;
Hazelaar, Germa M. ;
Heringhaus, Christian ;
Hofstee, Herman ;
Hovens, Marcel M. C. ;
Kaasjager, Karin A. H. ;
van Klink, Rick C. J. ;
Kruip, Marieke J. H. A. ;
Loeffen, Rinske F. ;
Mairuhu, Albert T. A. ;
Middeldorp, Saskia ;
Nijkeuter, Mathilde ;
van der Pol, Liselotte M. ;
Schol-Gelok, Suzanne ;
ten Wolde, Marije ;
Klok, Frederikus A. ;
Huisman, Menno V. .
LANCET, 2017, 390 (10091) :289-297
[17]   Ethyl pyruvate exerts combined anti-inflammatory and anticoagulant effects on human monocytic cells [J].
van Zoelen, Marieke A. D. ;
Bakhtiari, Kamran ;
Dessing, Mark C. ;
van 't Veer, Cornelis ;
Spek, C. Arnold ;
Tanck, Michael ;
Meijers, Joost C. ;
van der Poll, Tom .
THROMBOSIS AND HAEMOSTASIS, 2006, 96 (06) :789-793
[18]   Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity [J].
Vanderbeke, L. ;
Van Mol, P. ;
Van Herck, Y. ;
De Smet, F. ;
Humblet-Baron, S. ;
Martinod, K. ;
Antoranz, A. ;
Arijs, I. ;
Boeckx, B. ;
Bosisio, F. M. ;
Casaer, M. ;
Dauwe, D. ;
De Wever, W. ;
Dooms, C. ;
Dreesen, E. ;
Emmaneel, A. ;
Filtjens, J. ;
Gouwy, M. ;
Gunst, J. ;
Hermans, G. ;
Jansen, S. ;
Lagrou, K. ;
Liston, A. ;
Lorent, N. ;
Meersseman, P. ;
Mercier, T. ;
Neyts, J. ;
Odent, J. ;
Panovska, D. ;
Penttila, P. A. ;
Pollet, E. ;
Proost, P. ;
Qian, J. ;
Quintelier, K. ;
Raes, J. ;
Rex, S. ;
Saeys, Y. ;
Sprooten, J. ;
Tejpar, S. ;
Testelmans, D. ;
Thevissen, K. ;
Van Buyten, T. ;
Vandenhaute, J. ;
Van Gassen, S. ;
Velasquez Pereira, L. C. ;
Vos, R. ;
Weynand, B. ;
Wilmer, A. ;
Yserbyt, J. ;
Garg, A. D. .
NATURE COMMUNICATIONS, 2021, 12 (01)