Association of D-dimer and Fibrinogen With Hypercoagulability in COVID-19 Requiring Extracorporeal Membrane Oxygenation

  1. Abhimanyu Chandel
  2. Saloni Patolia
  3. Mary Looby
  4. Najeebah Bade
  5. Vikramjit Khangoora
  6. Christopher S. King

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Abstract

D-dimer concentration has been used by institutions to identify candidates for intensified anticoagulant treatment for venous thromboembolism prevention and for the mitigation of the microthrombotic complications associated with COVID-19. Thromboelastography (TEG) maximum amplitude (MA) has been validated as a marker of hypercoagulability and MA ≥68 mm has been utilized as a marker of hypercoagulability in other conditions.

Methods:

The goal of this study was to evaluate the relationship between coagulation, inflammatory, and TEG parameters in patients with COVID-19 on extracorporeal membrane oxygenation (ECMO). We performed a single-center retrospective analysis of consecutive patients that received ECMO for the treatment of COVID-19. TEG, inflammatory, and coagulation markers were compared in patients with and without a thrombotic complication. Correlation tests were performed to identify the coagulation and inflammatory markers that best predict hypercoagulability as defined by an elevated TEG MA.

Results:

A total of 168 TEGs were available in 24 patients. C-reactive protein and fibrinogen were significantly higher in patients that developed a thrombotic event versus those that did not ( P = 0.04 and P = 0.04 respectively). D-dimer was negatively correlated with TEG MA ( P < 0.01), while fibrinogen was positively correlated ( P < 0.01). A fibrinogen >441 mg/dL was found to have a sensitivity of 91.2% and specificity of 85.7% for the detection of MA ≥68 mm.

Conclusions:

In critically ill patients with COVID-19 treated with ECMO, D-dimer concentration had an inverse relationship with degree of hypercoagulability as measured by TEG MA. D-dimer elevation may potentially reflect hemostatic perturbation in patients on ECMO or the severity of COVID-19 related sepsis rather than designate patients likely to benefit from anticoagulation. Fibrinogen concentration may represent a more useful marker of hypercoagulability in this population.

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  1. Version published to 10.1177/0885066621997039
  2. ScreenIT

    SciScore for 10.1101/2020.07.27.20162842: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was approved by the Institutional Review Board (IRB# 18-3317) at Inova Fairfax Hospital.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All statistical analyses were performed using STATA version 14 (StataCorp LP; College Station, TX, USA).
    STATA
    suggested: (Stata, RRID:SCR_012763)
    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:
    Our findings should be interpreted in the context of the study limitations. First, our data is retrospectively derived from a single tertiary care center. The study was limited to severe COVID-19 infection requiring ECMO support to facilitate data collection due to the institutional use of TEG as part of the standard care of these patients. Alterations in platelet function is a known phenomenon in patients on ECMO and the implications of this alteration may affect TEG, inflammatory, and coagulation parameters.[19] Microvesicles are particles derived from platelets or monocytes and carry procoagulant activity. Microvesicles have been associated with VTE and have also been noted in patients on ECMO.[20] The interplay between COVID-19 disease and the effects of ECMO may also increase the risk of thromboembolism in these patients. Given these considerations, our selected population may limit generalizability and our findings should be validated in a non-ECMO cohort. Second, all patients in our study were on therapeutic anticoagulation with either heparin or bivalirudin per standard institutional ECMO protocol. Deviation from protocolized dosing of therapeutic anticoagulation was occasionally noted. Several of the patients in this report experienced clotting at cannulation sites despite boluses of heparin and one patient received tissue plasminogen activator in addition to anticoagulation for repetitive pulmonary emboli. There is limited data regarding the use of bivalirudin in pa...

    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.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. ScreenIT

    SciScore for 10.1101/2020.07.27.20162842: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementThe study was approved by the Institutional Review Board (IRB# 18-3317) at Inova Fairfax Hospital.Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All statistica analyses were performed using STATA version 14 (StataCorp LP; College Station, TX, USA).
    STATA
    suggested: (Stata, SCR_012763)
          <div style="margin-bottom:8px">
        <div><b>StataCorp</b></div>
        <div>suggested: (Stata, <a href="https://scicrunch.org/resources/Any/search?q=SCR_012763">SCR_012763</a>)</div>
      </div>
    </td></tr></table>

    Data from additional tools added to each annotation on a weekly basis.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.07.27.20162842v1 on medRxiv