Hypercoagulation Detected by Rotational Thromboelastometry Predicts Mortality in COVID-19: A Risk Model Based on a Prospective Observational Study

  1. Lou M. Almskog
  2. Agneta Wikman
  3. Jonas Svensson
  4. Matteo Bottai
  5. Mariann Kotormán
  6. Carl-Magnus Wahlgren
  7. Michael Wanecek
  8. Jan van der Linden
  9. Anna Ågren

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Abstract

Background Severe disease due to the novel coronavirus disease 2019 (COVID-19) has been shown to be associated with hypercoagulation. The aim of this study was to assess the Rotational Thromboelastometry (ROTEM) as a marker of coagulopathy in hospitalized COVID-19 patients.

Methods This was a prospective, observational study where patients hospitalized due to a COVID-19 infection were eligible for inclusion. Conventional coagulation tests and ROTEM were taken after hospital admission, and patients were followed for 30 days. A prediction model, including variables ROTEM EXTEM-MCF (Maximum Clot Firmness) which in previous data has been suggested a suitable marker of hypercoagulation, age, and respiratory frequency, was developed using logistic regression to evaluate the probability of death.

Results Out of the 141 patients included, 18 (13%) died within 30 days. In the final prediction model, the risk of death within 30 days for a patient hospitalized due to COVID-19 was increased with increased EXTEM-MCF, age, and respiratory frequency. Longitudinal ROTEM data in the severely ill subpopulation showed enhanced hypercoagulation. In an in vitro analysis, no heparin effect on EXTEM–coagulation time (CT) was observed, supporting a severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) effect on prolonged initiation of coagulation.

Conclusion Here, we show that hypercoagulation measured with ROTEM predicts 30-day mortality in COVID-19. Longitudinal ROTEM data strengthen the hypothesis of hypercoagulation as a driver of severe disease in COVID-19. Thus, ROTEM may be a useful tool to assess disease severity in COVID-19 and could potentially guide anticoagulation therapy.

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  1. Version published to 10.1055/a-1725-9221
  2. ScreenIT

    SciScore for 10.1101/2021.04.29.21256241: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: In the ethical approval consent was waivered in severe cases of COVID-19 disease, where patients due to medical conditions were not able to give their consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Stata statistical software, version 15 (StataCorp LLC) and R, version 3.6.1 was used for statistical analysis and visualizations.
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Some limitations of this study should be recognized: 1) The sample size was relatively small. 2) Some patients were included somewhat later than the day of admission, which may have reflected test results of different disease stages. 3) Most patients had received antithrombotic treatment prior to inclusion, which may have influenced our lab results. However, given that the ROTEM variable we chose to include as a predictor indicated hypercoagulopathy, we do not presume this created any false positive associations. The recruitment of patients was performed at a single site with no validation set. The applicability of the model therefore needs to be validated in larger independent cohorts, in order to confirm its generalizability in other settings and populations. These limitations notwithstanding, we consider our cohort as a representative sample from the first wave of COVID-19 in Stockholm, in which a state of hypercoagulability has been shown to be associated with an increased risk of death. Together, these results indicate that ROTEM is a useful analysing method of coagulopathy in COVID-19 and may be a promising tool to guide anticoagulant treatment.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a protocol registration statement.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  3. Version published to 10.1101/2021.04.29.21256241v1 on medRxiv