The usefulness of D-dimer as a predictive marker for mortality in patients with COVID-19 hospitalized during the first wave in Italy

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Abstract

The coronavirus disease 2019 (COVID-19) presents an urgent threat to global health. Identification of predictors of poor outcomes will assist medical staff in treatment and allocating limited healthcare resources.

Aims

The primary aim was to study the value of D-dimer as a predictive marker for in-hospital mortality.

Methods

This was a cohort study. The study population consisted of hospitalized patients (age >18 years), who were diagnosed with COVID-19 based on real-time PCR at 9 hospitals during the first COVID-19 wave in Lombardy, Italy (Feb-May 2020). The primary endpoint was in-hospital mortality. Information was obtained from patient records. Statistical analyses were performed using a Fine-Gray competing risk survival model. Model discrimination was assessed using Harrell’s C-index and model calibration was assessed using a calibration plot.

Results

Out of 1049 patients, 507 patients (46%) had evaluable data. Of these 507 patients, 96 died within 30 days. The cumulative incidence of in-hospital mortality within 30 days was 19% (95CI: 16%-23%), and the majority of deaths occurred within the first 10 days. A prediction model containing D-dimer as the only predictor had a C-index of 0.66 (95%CI: 0.61–0.71). Overall calibration of the model was very poor. The addition of D-dimer to a model containing age, sex and co-morbidities as predictors did not lead to any meaningful improvement in either the C-index or the calibration plot.

Conclusion

The predictive value of D-dimer alone was moderate, and the addition of D-dimer to a simple model containing basic clinical characteristics did not lead to any improvement in model performance.

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  1. SciScore for 10.1101/2022.02.04.22270433: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was approved by the Medical Ethics Committee of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico.
    Consent: Written informed consent was obtained from patients before data collection.
    Sex as a biological variableThe following patient-and treatment characteristics were obtained: age (continuous variable), sex (dichotomous variable; male, female), the use of anticoagulant therapy during the study (dichotomous variable; yes, no) and the number of days between symptom onset and hospital admission (continuous variable).
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisSample size calculation: A formal sample size calculation for the development of a prediction model was not performed.

    Table 2: Resources

    No key resources detected.


    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:
    [22] Our study also has some limitations. The main limitation is that values for D-dimer levels were not available for 506 out of 1094 patients. D-dimer tests are most commonly ordered if a patient has some symptoms or medical history which are indicative of a thromboembolic event. Therefore, patients that were excluded from the study due to missing information on D-dimer were most likely patients with a low a priori likelihood of having a VTE. Also, D-dimer assays vary widely in their set-up. This lack of standardization makes comparison of different study results somewhat difficult. [23,24] Due to the rapid pace of change in the treatment of patients with COVID-19, the predictive value of D-dimer (and therefore, it’s clinical usefulness) will most likely have diminished over time. For example, in Lombardy, many patients in the second COVID-19 wave (Oct-Dec 2020) were already being prescribed anticoagulant treatment by their general practitioner before hospitalization. Furthermore, as the outbreak went on, patients with milder symptoms were also being hospitalized. Due to these treatment changes, we can speculate that patients hospitalized after the first COVID-19 wave will have had lower D-dimer levels at admission, when compared to patients admitted in the first COVID-19 wave (Feb-May 2020). Furthermore, D-dimer levels would have been less strongly associated with mortality in these patients, when compared to patients admitted in the first COVID-19 wave (Feb-May 2020). As ...

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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


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