Markers Of Coagulation And Hemostatic Activation Identify COVID-19 Patients At High Risk For Thrombotic Events, ICU Admission and Intubation

  1. Darwish Alabyad
  2. Srikant Rangaraju
  3. Michael Liu
  4. Rajeel Imran
  5. Christine L. Kempton
  6. Milad Sharifpour
  7. Sara C. Auld
  8. Manila Gaddh
  9. Roman Sniecinski
  10. Cheryl L. Maier
  11. Jeannette Guarner
  12. Alexander Duncan
  13. Fadi Nahab

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Abstract

Background

Coronavirus disease 2019 (COVID-19) has been associated with a coagulopathy giving rise to venous and arterial thrombotic events. The objective of our study was to determine whether markers of coagulation and hemostatic activation (MOCHA) on admission could identify COVID-19 patients at risk for thrombotic events and other complications.

Methods

COVID-19 patients admitted to a tertiary academic healthcare system from April 3, 2020 to July 31, 2020 underwent standardized admission testing of MOCHA profile parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) with abnormal MOCHA defined as ≥ 2 markers above the reference. Prespecified thrombotic endpoints included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, and access line thrombosis; other complications included ICU admission, intubation and mortality. We excluded patients on anticoagulation therapy prior to admission and those who were pregnant.

Results

Of 276 patients (mean age 59 ± 6.4 years, 47% female, 62% African American race) who met study criteria, 45 (16%) had a thrombotic event. Each coagulation marker on admission was independently associated with a vascular endpoint (p<0.05). Admission MOCHA with ≥ 2 abnormalities (n=203, 74%) was associated with in-hospital vascular endpoints (OR 3.3, 95% CI 1.2-8.8), as were admission D-dimer ≥ 2000 ng/mL (OR 3.1, 95% CI 1.5-6.6), and admission D-dimer ≥ 3000 ng/mL (OR 3.6, 95% CI 1.6-7.9). However, only admission MOCHA with ≥ 2 abnormalities was associated with ICU admission (OR 3.0, 95% CI 1.7-5.2) and intubation (OR 3.2, 95% CI 1.6-6.4), while admission D-dimer ≥2000 ng/mL and admission D-dimer ≥ 3000 ng/mL were not associated. MOCHA and D-dimer cutoffs were not associated with mortality. Admission MOCHA with <2 abnormalities (26% of the cohort) had a sensitivity of 88% and negative predictive value of 93% for a vascular endpoint.

Conclusions

Admission MOCHA with ≥ 2 abnormalities identified COVID-19 patients at increased risk of ICU admission and intubation during hospitalization more effectively than isolated admission D-dimer measurement. Admission MOCHA with <2 abnormalities identified a subgroup of patients at low risk for vascular events. Our results suggest that an admission MOCHA profile can be useful to risk-stratify COVID-19 patients.

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  1. ScreenIT

    SciScore for 10.1101/2020.10.04.20206540: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the Emory University Institutional Review Board.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Study Design and Setting: Patients were prospectively identified from an admission census list that identified all COVID-19 patients admitted to four hospitals in Emory Healthcare, an urban, academic, tertiary healthcare system in Atlanta, Georgia who had a MOCHA profile ordered on admission as part of a standardized COVID-19 orderset from April 3, 2020 through July 31, 2020.
    Emory Healthcare
    suggested: (One Mind Biospecimen Bank Listing, RRID:SCR_004193)
    Statistical analyses and figures were generated using SPSS version 26 software.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    This study had several limitations. As the data was collected from a single academic healthcare system, the generalizability of these findings needs to be studied in other settings. Our study focused on admission coagulation markers to aid in early risk stratification for COVID-19 patients however it is unknown whether serial measurements and changes in values across time may be better predictors. Lastly, our study did not assess whether the MOCHA profile could be used to guide anticoagulation therapy and how that may impact overall thrombotic events and clinical outcome. In summary, the admission MOCHA profile of hospitalized COVID-19 patients is useful in identifying hospitalized patients who are at increased risk for subsequent arterial and venous thrombotic events and more effectively identifies patients requiring ICU admission and intubation than admission D-dimer levels alone. Further investigation is needed to determine the utility of the MOCHA profile to guide anticoagulation therapy.

    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.

    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.

  2. Version published to 10.1101/2020.10.04.20206540 on medRxiv