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. 2020 Oct 13;4(7):1178-1191.
doi: 10.1002/rth2.12439. eCollection 2020 Oct.

Risk of venous thromboembolism in patients with COVID-19: A systematic review and meta-analysis

Stephan Nopp  1 , Florian Moik  1 , Bernd Jilma  2 , Ingrid Pabinger  1 , Cihan Ay  1   3
Affiliations

Risk of venous thromboembolism in patients with COVID-19: A systematic review and meta-analysis

Stephan Nopp et al. Res Pract Thromb Haemost. .

Abstract

Background: Venous thromboembolism (VTE) is frequently observed in patients with coronavirus disease 2019 (COVID-19). However, reported VTE rates differ substantially.

Objectives: We aimed at evaluating available data and estimating the prevalence of VTE in patients with COVID-19.

Methods: We conducted a systematic literature search (MEDLINE, EMBASE, World Health Organization COVID-19 database) to identify studies reporting VTE rates in patients with COVID-19. Studies with suspected high risk of bias were excluded from quantitative synthesis. Pooled outcome rates were obtained within a random effects meta-analysis. Subgroup analyses were performed for different settings (intensive care unit [ICU] vs non-ICU hospitalization and screening vs no screening) and the association of d-dimer levels and VTE risk was explored.

Results: Eighty-six studies (33,970 patients) were identified and 66 (28,173 patients, mean age: 62.6 years, 60.1% men, 19.4% ICU patients) were included in quantitative analysis. The overall VTE prevalence estimate was 14.1% (95% confidence interval [CI], 11.6-16.9), 40.3% (95% CI, 27.0-54.3) with ultrasound screening and 9.5% (95% CI, 7.5-11.7) without screening. Subgroup analysis revealed high heterogeneity, with a VTE prevalence of 7.9% (95% CI, 5.1-11.2) in non-ICU and 22.7% (95% CI, 18.1-27.6) in ICU patients. Prevalence of pulmonary embolism (PE) in non-ICU and ICU patients was 3.5% (95% CI, 2.2-5.1) and 13.7% (95% CI, 10.0-17.9). Patients developing VTE had higher d-dimer levels (weighted mean difference, 3.26 µg/mL; 95% CI, 2.76-3.77) than non-VTE patients.

Conclusion: VTE occurs in 22.7% of patients with COVID-19 in the ICU, but VTE risk is also increased in non-ICU hospitalized patients. Patients developing VTE had higher d-dimer levels. Studies evaluating thromboprophylaxis strategies in patients with COVID-19 are needed to improve prevention of VTE.

Keywords: COVID‐19; prevalence; pulmonary embolism; severe acute respiratory syndrome coronavirus 2; venous thromboembolism.

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Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) flow diagram for study selection
Figure 2
Figure 2
Prevalence of VTE in patients with COVID‐19. Prevalence of VTE is estimated based on 66 studies and stratified by the performance of ultrasound screening for VTE. The overall VTE prevalence was 14.1% (95% CI, 11.6‐16.9), 40.3% (95% CI, 27.0‐54.3) in those screened and 9.5% (95% CI, 7.5‐11.7) in those not screened. Red diamonds represent subtotal (screening studies vs nonscreening studies) and overall prevalence estimates and corresponding 95% CI of VTE outcomes. VTE comprises the specific outcome as reported by the respective study (PE and/or DVT). Details on each study are listed in Tables S1 and S2. CI, confidence interval; DVT, deep vein thrombosis; ECMO, extracorporeal membrane oxygenation; ES, estimates; mech. vent., mechanically ventilated; ICU, intensive care unit; PE, pulmonary embolism; VTE, venous thromboembolism
Figure 3
Figure 3
Differences in baseline d‐dimer between patients with VTE and patients without VTE. Patients developing VTE had higher baseline d‐dimer levels compared to those without VTE. D‐dimer levels at baseline were available in 21 studies, including 6633 patients. In the pooled analysis, levels of d‐dimer were substantially higher at baseline in patients experiencing VTE (WMD, 3.26 µg/mL (95% CI, 2.76‐3.77; P < .001; I2, 87.3%). CI, confidence interval; VTE, venous thromboembolism; WMD, weighted mean difference
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