Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar;126(3):590-598.
doi: 10.1016/j.bja.2020.12.010. Epub 2020 Dec 9.

Impaired fibrinolysis in critically ill COVID-19 patients

Mirjam Bachler  1 , Johannes Bösch  2 , Daniel P Stürzel  3 , Tobias Hell  4 , Andreas Giebl  5 , Mathias Ströhle  3 , Sebastian J Klein  6 , Volker Schäfer  3 , Georg F Lehner  6 , Michael Joannidis  6 , Claudius Thomé  7 , Dietmar Fries  3
Affiliations

Impaired fibrinolysis in critically ill COVID-19 patients

Mirjam Bachler et al. Br J Anaesth. 2021 Mar.

Abstract

Background: Critically ill coronavirus disease 2019 (COVID-19) patients present with a hypercoagulable state with high rates of macrovascular and microvascular thrombosis, for which hypofibrinolysis might be an important contributing factor.

Methods: We retrospectively analysed 20 critically ill COVID-19 patients at Innsbruck Medical University Hospital whose coagulation function was tested with ClotPro® and compared with that of 60 healthy individuals at Augsburg University Clinic. ClotPro is a viscoelastic whole blood coagulation testing device. It includes the TPA test, which uses tissue factor (TF)-activated whole blood with added recombinant tissue-derived plasminogen activator (r-tPA) to induce fibrinolysis. For this purpose, the lysis time (LT) is measured as the time from when maximum clot firmness (MCF) is reached until MCF falls by 50%. We compared COVID-19 patients with prolonged LT in the TPA test and those with normal LT.

Results: Critically ill COVID-19 patients showed hypercoagulability in ClotPro assays. MCF was higher in the EX test (TF-activated assay), IN test (ellagic acid-activated assay), and FIB test (functional fibrinogen assay) with decreased maximum lysis (ML) in the EX test (hypofibrinolysis) and highly prolonged TPA test LT (decreased fibrinolytic response), as compared with healthy persons. COVID-19 patients with decreased fibrinolytic response showed higher fibrinogen levels, higher thrombocyte count, higher C-reactive protein levels, and decreased ML in the EX test and IN test.

Conclusion: Critically ill COVID-19 patients have impaired fibrinolysis. This hypofibrinolytic state could be at least partially dependent on a decreased fibrinolytic response.

Keywords: COVID-19; D-dimer; coagulation; critically ill; fibrinogen; fibrinolysis; tissue plasminogen activator; viscoelastic test.

PubMed Disclaimer

Conflict of interest statement

Declarations of interest MB has received research funding and travel grants from LFB Biomedicaments, Baxter GmbH, CSL Behring GmbH, Mitsubishi Tanabe and non-financial support from TEM International outside the submitted work. MJ reported receiving grants from Baxter; grants and personal fees from Fresenius Kabi; and speaking, consulting honoraria, or both from Sphingotec, CLS-Behring, Fresenius and Astute Medical outside the submitted work. CT reports grants and personal fees from BrainLab, grants and personal fees from DePuySynthes, grants and personal fees from Intrinsic Therapeutics, grants from TETEC AG, personal fees from Aesculap, grants and personal fees from Signus Medizintechnik, grants and personal fees from Medtronic, grants and personal fees from Icotec AG, grants and personal fees from Edge Therapeutics, grants from BIT-Pharma, outside the submitted work. DF has received study funding, honoraria for consultancy and board activity from Astra Zeneca, AOP orphan, Baxter, Bayer, BBraun, Biotest, CSL Behring, Delta Select, Dade Behring, Edwards, Fresenius, Glaxo, Haemoscope, Hemogem, Lilly, LFB, Mitsubishi Pharma, NovoNordisk, Octapharm, Pfizer, Tem-Innovation outside the submitted work. The other authors declare no conflicts of interest.

Figures

Fig 1
Fig 1
Decreased fibrinolytic response in critically ill COVID-19 patients. The numbers below the box plots depict median (25th to 75th percentile) and estimated median differences with corresponding 95% confidence intervals (CIs) and P-value. (a) Prolonged lysis time (LT) in the TPA test assay in critically ill COVID-19 patients as compared with healthy persons. Fibrinogen levels (b), platelet counts (d), and levels of C-reactive protein (e) were significantly elevated in patients with decreased fibrinolytic response, whereas D-dimers did not differ between patients with and without impaired fibrinolysis (c).
See this image and copyright information in PMC

Comment in

References

    1. World Health Organization . 7 September 2020. Epidemiological Update, Coronavirus disease 2019 (COVID-19)https://www.who.int/docs/default-source/coronaviruse/situation-reports/2... Available from:
    1. Morens D.M., Daszak P., Markel H., Taubenberger J.K. Pandemic COVID-19 joins history’s pandemic legion. mBio. 2020;11:e00812–e00820. - PMC - PubMed
    1. Spiezia L., Boscolo A., Poletto F. COVID-19-related severe hypercoagulability in patients admitted to intensive care unit for acute respiratory failure. Thromb Haemost. 2020;120:998–1000. - PMC - PubMed
    1. Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844–847. - PMC - PubMed
    1. Zhou F., Yu T., Du R. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062. - PMC - PubMed

Substances

LinkOut - more resources