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Another new application of heparin in COVID-19: more than anticoagulation and antiviral

Xianqiang Yu
DOI: 10.1136/jim-2021-001951 Published 26 July 2021
Xianqiang Yu
Medical School, Southeast University–Dingjiaqiao Campus, Nanjing, Jiangsu, China
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Dear Editor,

We read with great interest an article in your journal about the relationship between heparin dose and anticoagulation effect of COVID-19 infection.1 As the pandemic continues to spread and challenge, it is particularly important to standardize treatment protocols for COVID-19 anticoagulation. To the best of our knowledge, heparin-binding protein (HBP) has important clinical value as an early predictor of COVID-19 and its combination with heparin plays a key role in anticoagulant therapy.2 In particular, the latest reports have unprecedentedly confirmed the anti-inflammatory mechanism of heparin in sepsis. From this perspective, heparin may play a double-edged sword effect in the anti-inflammatory and anticoagulant effects of severe COVID-19.

It is reported that heparin inhibited HMGB1–lipopolysaccharide interactions and prevented macrophage heparinase from degrading glycocalyx.3 HMGB1 is a well-studied component of the damage-associated molecular pattern family. As a key potential therapeutic target in the occurrence and development of sepsis, it has always been the target of drug exploration. It is well known that heparin is a pluripotent drug for clinical favor, including anticoagulant, lipid-lowering, anti-inflammatory, and so on. But to be clear, little is known about the mechanism by which heparin exacts its anti-inflammatory effects. We also noted that even if the anticoagulant part of heparin was removed, it could also play a significant anti-inflammatory effect in sepsis through the HMGB1 pathway. In other words, modified heparin can be used in inflammatory diseases without concern for its classical pharmacological side effects. Severe COVID-19 is often faced with a combination of severe inflammation and coagulation disorders. In particular, elevated HBP levels in patients with severe COVID-19 provide the possibility of carrying exogenous heparin. Therefore, from this point of view, heparin has multiple clinical values of anticoagulation and anti-inflammatory in the treatment of severe COVID-19. We have noted that there are currently a series of randomized controlled trials of heparin in the treatment of COVID-19 anticoagulants. Therefore, the next focus should be to consider which patients with COVID-19 will benefit from heparin treatment, which will not, and which may even be impaired. With this in mind, the appropriate range of heparin in the treatment of patients with COVID-19 and the balance of its anticoagulant and anti-inflammatory doses are urgently needed to be clarified.

As the pandemic continues to spread and brings uncertain risks, targeted intervention drugs for severe COVID-19 are of far-reaching significance. In particular, heparin, as a potentially effective anti-inflammatory agent in severe patients, combined with its own anticoagulant effect may play a significant role in the treatment of severe COVID-19. The clarity of the anti-inflammatory mechanism of heparin through HMGB1 pathway gives us sufficient confidence in its potential anti-inflammatory value in patients with severe COVID-19. After all, there is reason to be optimistic about heparin as a new trial for an old drug.

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Footnotes

  • Contributors XY completed the design and writing of the article and all the relevant contents of the manuscript.

  • Funding This study was funded by Scholarship of Southeast University (No 189351).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

References

  1. ↵
    1. Carallo C ,
    2. Pugliese F ,
    3. Vettorato E , et al
    . Higher heparin dosages reduce thromboembolic complications in patients with COVID-19 pneumonia. J Investig Med 2021;69:884–7.doi:10.1136/jim-2020-001628 pmid:http://www.ncbi.nlm.nih.gov/pubmed/33758036
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Saridaki M ,
    2. Metallidis S ,
    3. Grigoropoulou S , et al
    . Integration of heparin-binding protein and interleukin-6 in the early prediction of respiratory failure and mortality in pneumonia by SARS-CoV-2 (COVID-19). Eur J Clin Microbiol Infect Dis 2021. doi:doi:10.1007/s10096-020-04145-7. [Epub ahead of print: 29 Jan 2021].pmid:http://www.ncbi.nlm.nih.gov/pubmed/33515095
  3. ↵
    1. Tang Y ,
    2. Wang X ,
    3. Li Z , et al
    . Heparin prevents caspase-11-dependent septic lethality independent of anticoagulant properties. Immunity 2021;54:454–67.doi:10.1016/j.immuni.2021.01.007 pmid:http://www.ncbi.nlm.nih.gov/pubmed/33561388
    OpenUrlPubMed
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Vol 69 Issue 6 Table of Contents
Journal of Investigative Medicine: 69 (6)
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Another new application of heparin in COVID-19: more than anticoagulation and antiviral
Xianqiang Yu
Journal of Investigative Medicine Aug 2021, 69 (6) 1258; DOI: 10.1136/jim-2021-001951

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Another new application of heparin in COVID-19: more than anticoagulation and antiviral
Xianqiang Yu
Journal of Investigative Medicine Aug 2021, 69 (6) 1258; DOI: 10.1136/jim-2021-001951
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Another new application of heparin in COVID-19: more than anticoagulation and antiviral
Xianqiang Yu
Journal of Investigative Medicine Aug 2021, 69 (6) 1258; DOI: 10.1136/jim-2021-001951
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