Estimating incidence of venous thromboembolism in COVID‐19: Methodological considerations

Abstract

Background Coagulation abnormalities and coagulopathy are recognized as consequences of severe acute respiratory syndrome coronavirus 2 infection and the resulting coronavirus disease 2019 (COVID‐19). Specifically, venous thromboembolism (VTE) has been reported as a frequent complication. By May 27, 2021, at least 93 original studies and 25 meta‐analyses investigating VTE incidence in patients with COVID‐19 had been published, showing large heterogeneity in reported VTE incidence ranging from 0% to 85%. This large variation complicates interpretation of individual study results as well as comparisons across studies, for example, to investigate changes in incidence over time, compare subgroups, and perform meta‐analyses. Objectives This study sets out to provide an overview of sources of heterogeneity in VTE incidence studies in patients with COVID‐19, illustrated using examples. Methods The original studies of three meta‐analyses were screened and a list of sources of heterogeneity that may explain observed heterogeneity across studies was composed. Results The sources of heterogeneity in VTE incidence were classified as clinical sources and methodologic sources. Clinical sources of heterogeneity include differences between studies regarding patient characteristics that affect baseline VTE risk and protocols used for VTE testing. Methodologic sources of heterogeneity include differences in VTE inclusion types, data quality, and the methods used for data analysis. Conclusions To appreciate reported estimates of VTE incidence in patients with COVID‐19 in relation to its etiology, prevention, and treatment, researchers should unambiguously report about possible clinical and methodological sources of heterogeneity in those estimates. This article provides suggestions for that.

Incidence and determinants of venous thromboembolism over 90 days in hospitalized and nonhospitalized patients with COVID‐19

“…The variations in reported prevalence rates are influenced by the large differences in study designs and populations, including data quality, threshold for hospitalization or transfer to the ICU, use of thromboprophylaxis, patient characteristics, and methods to ascertain the outcome. Thus, comparing incidence rates is difficult [32]. A meta‐analysis from 2021 reported a pooled incidence for VTE in hospitalized COVID‐19 patients of 17% [33].…”

Risk Factors for Postdischarge Major Thromboembolism and Mortality in Hospitalized Patients with COVID-19 with Cardiovascular Comorbidities: Insights from the CORE-19 Registry

“…5,6 Thrombotic microangiopathy is manifested as thrombocytopenia, microangiopathic hemolytic anemia, end organ damage, and pulmonary capillary stasis/microthrombi that occur despite anticoagulation. Studies reporting pooled inpatient rates of COVID-19-associated thrombosis are subject to high heterogeneity, 7 though pooled rates for the early pandemic are 10 to 15% for VTE, 8-10 and 3 to 5% for ATE. 8,11 High rates of undiagnosed pulmonary microthrombi at the time of death also suggest an association between thromboembolism and mortality.…”

Does COVID-19 vaccination protect against pulmonary embolism?

“…The prevalence of venous thromboembolism (VTE) in patients with COVID-19 is highly variable, depending on methodological and clinical factors, among which vaccination [ 1 ]. The hypothesis of a possible protective role of vaccination in preventing pulmonary embolism (PE) in hospitalized COVID-19 patients has not been explored.…”