Skip to main content

Plasma exchange in critically ill COVID-19 patients improved inflammation, microcirculatory clot formation, and hypotension, thereby improving clinical outcomes: fact or fiction?

We read with great interest the recent article by Morath et al. who conclude that plasma exchange (PE) improved inflammation, microcirculatory clot formation, and hypotension, thereby improving clinical outcomes [1]. We would like to make some comments. This is a good example of when misinterpretation of the results can lead to the wrong conclusions. PE has a cutoff of 1,000,000 daltons (Da) and can therefore remove many substances. Let us just take the example of the inflammatory mediators C-reactive protein (CRP) and interleukin-6 (IL-6). CRP, in its pentameric form, has a molecular weight of 120,000 Da and in its monomeric form 22,000 Da [2]. IL-6 has a molecular weight of 21,000 Da [3]. It stands to reason that these two inflammatory molecules will be easily removed by PE. Reduction of the plasma level of inflammatory mediators via the use of PE does not necessarily equate to an improvement in the septic status of the patient. It is simply an artificial reduction, “treating the numbers” so to speak. The same is true for ferritin (474,000 Da), LDH (144,000 Da), and D-dimers (180,000 Da), where the observed reduction is simply a consequence of removal and not an improvement of the patient’s condition. It is also important to note that PE has the potential to cause harm by diluting or attenuating the patient’s adaptive response to infection via depletion of immunoglobulins and complement components 3 and 4 in individuals treated with plasmapheresis [4]. Importantly, in the case of patients with COVID-19, PE will remove the protective antibodies formed by the patient, which is not desirable. Indeed, PE may not restore immune homeostasis but may rather aggravate immunoparalysis [5]. Look also at the various additional treatments received by the patients: tocilizumab, interferon, prednisolone, immunoglobulins, and convalescent serum [1]. Most of these additional treatments will be easily removed by PE. The authors stated that clinical improvements were achieved with only 1 to 2 PE, possibly indicating a direct pathophysiological influence of PE on the COVID-19-associated cytokine storm-like clinical syndrome [1]. We doubt that this is the case. The only positive effect that we can see is in the control of temperature; perhaps by inducing relative hypothermia, PE resulted in peripheral vasoconstriction responsible for the weaning of vasopressors.

Availability of data and materials

Not applicable.

Abbreviations

PE:

Plasma exchange

Da:

Daltons

CRP:

C-reactive protein

IL-6:

Interleukin-6

LDH:

Lactate dehydrogenase

References

  1. 1.

    Morath C, Weigand MA, Zeier M, Speer C, Tiwari-Heckler S, Merle U. Plasma exchange in critically ill COVID-19 patients. Crit Care. 2020;24:481. https://doi.org/10.1186/s13054-020-03171-3.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Honore PM, Jacobs R, Hendrickx I, De Waele E, Van Gorp V, Spapen HD. ‘Biomarking’ infection during continuous renal replacement therapy: still relevant? Crit Care. 2015;19(1):232. https://doi.org/10.1186/s13054-015-0948-z.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Tosato G, Tanner J, Jones KD, Revel M, Pike SE. Identification of interleukin-6 as an autocrine growth factor for Epstein-Barr virus-immortalized B cells. J Virol. 1990;64(6):3033–41. https://doi.org/10.1128/JVI.64.6.3033-3041.1990.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Rimmer E, Houston BL, Kumar A, Abou-Setta AM, Friesen C, Marshall JC, et al. The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis. Crit Care. 2014 Dec 20;18(6):699. https://doi.org/10.1186/s13054-014-0699-2.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Szczeklik W, Wawrzycka K, Włudarczyk A, Sega A, Nowak I, Seczyńska B, et al. Complications in patients treated with plasmapheresis in the intensive care unit. Anaesthesiol Intensive Ther. 2013 Jan-Mar;45(1):7–13. https://doi.org/10.5603/AIT.2013.0002.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

None.

Funding

None.

Author information

Affiliations

Authors

Contributions

PMH, SR, and DDB designed the paper. All authors participated in drafting and reviewing. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Patrick M. Honore.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare to have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Honore, P.M., Barreto Gutierrez, L., Kugener, L. et al. Plasma exchange in critically ill COVID-19 patients improved inflammation, microcirculatory clot formation, and hypotension, thereby improving clinical outcomes: fact or fiction?. Crit Care 24, 551 (2020). https://doi.org/10.1186/s13054-020-03262-1

Download citation