Prevalence of Venous Thromboembolism in Critically Ill COVID-19 Patients: Systematic Review and Meta-Analysis

  1. Mouhand F. H. Mohamed
  2. Shaikha D. Al-Shokri
  3. Khaled M. Shunnar
  4. Sara F. Mohamed
  5. Mostafa S. Najim
  6. Shahd I. Ibrahim
  7. Hazem Elewa
  8. Lina O. Abdalla
  9. Ahmed El-Bardissy
  10. Mohamed Nabil Elshafei
  11. Ibrahim Y. Abubeker
  12. Mohammed Danjuma
  13. Khalid M. Dousa
  14. Mohamed A. Yassin

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Abstract

Background: Recent studies revealed a high prevalence of venous thromboembolism (VTE) events in coronavirus disease 2019 (COVID-19) patients, especially in those who are critically ill. Available studies report varying prevalence rates. Hence, the exact prevalence remains uncertain. Moreover, there is an ongoing debate regarding the appropriate dosage of thromboprophylaxis.

Methods: We performed a systematic review and proportion meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and EMBASE for studies exploring the prevalence of VTE in critically ill COVID-19 patients till 25/07/2020. We pooled the proportion of VTE. Additionally, in a subgroup analysis, we pooled VTE events detected by systematic screening. Finally, in an exploratory analysis, we compared the odds of VTE in patients on prophylactic compared with therapeutic anticoagulation.

Results: The review comprised 24 studies and over 2,500 patients. The pooled proportion of VTE prevalence was 0.31 [95% confidence interval (CI) 0.24, 0.39; I 2 94%], of VTE utilizing systematic screening was 0.48 (95% CI 0.33, 0.63; I 2 91%), of deep venous thrombosis was 0.23 (95% CI 0.14, 0.32; I 2 96%), and of pulmonary embolism was 0.14 (95% CI 0.09, 0.20; I 2 90%). Exploratory analysis of few studies, utilizing systematic screening, VTE risk increased significantly with prophylactic, compared with therapeutic anticoagulation [odds ratio (OR) 5.45; 95% CI 1.90, 15.57; I 2 0%].

Discussion: Our review revealed a high prevalence of VTE in critically ill COVID-19 patients. Almost 50% of patients had VTE detected by systematic screening. Higher thromboprophylaxis dosages may reduce VTE burden in this patient's cohort compared with standard prophylactic anticoagulation; however, this is to be ascertained by ongoing randomized controlled trials.

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  1. ScreenIT

    SciScore for 10.1101/2020.08.24.20175745: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Information sources and literature search: For a timely review, we performed the search in PubMed, MEDLINE, and EMBASE.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)
    We used free text, emtree, and MeSH terms in our search.
    MeSH
    suggested: (MeSH, RRID:SCR_004750)
    We used the Cochrane Q test and I2 to examine heterogeneity.
    Cochrane Q
    suggested: None
    We used MetaXl software for statistical analysis (version 5.3 © EpiGear International Pty Ltd ABN 51 134 897 411 Sunrise Beach, Queensland, Australia, 2011-2016)
    MetaXl
    suggested: None

    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:
    Limitations of our review are the heterogeneity in the pooled prevalence in the constituent studies. This is likely due to varying detection methods (systematic vs. nonsystematic, imaging modalities used, timing, etc.), screening threshold (many studies reported that the threshold was high due to infection control concerns), varying severity of illness, prophylaxis strategies, and dosage, missing VTE in deceased patients of fatal VTE events, varying and insufficient follow-ups. Additionally, the inability to provide a mortality comparison between VTE group and non-VTE group due to data paucity (we contacted the primary authors; however, we could not get the data necessary for its computation), limited conclusion provided by the comparison of VTE in the therapeutic vs. prophylactic anticoagulation groups (absence of adjustment, varying doses between studies). Moreover, the retrospective nature of the included studies, inability to accurately compute the prevalence of PE (absence of systematic PE screening), and absence of autopsies to ascertain causes of death, adds to the limitations of our review. Notwithstanding this, there are many strengths to our review that are worthy of mention. This is the most extensive review examining the prevalence of VTE exclusively in critically ill patients. Additionally, the review examines VTE prevalence based on the utilized screening method providing the readers with a better estimate of VTE prevalence. We also pooled a proportion that refl...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04367831RecruitingIntermediate or Prophylactic-Dose Anticoagulation for Venous…
    NCT04373707RecruitingWeight-Adjusted vs Fixed Low Doses of Low Molecular Weight H…
    NCT04401293RecruitingFull Dose Heparin Vs. Prophylactic Or Intermediate Dose Hepa…

    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 10.3389/fcvm.2020.598846
  3. Version published to 10.1101/2020.08.24.20175745v1 on medRxiv