Development of venous thromboembolism and its impact on hospitalized adults with covid-19: rapid systematic review

Rocha, Andressa Pereira; Sanchez, João Gabriel

doi:10.1590/1677-5449.202400731

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Table of contents

REVIEW ARTICLES • J. Vasc. Bras. 24 • 2025 • https://doi.org/10.1590/1677-5449.202400732 linkcopy

Development of venous thromboembolism and its impact on hospitalized adults with covid-19: rapid systematic review

Authorship SCIMAGO INSTITUTIONS RANKINGS

The association between COVID-19 and coagulation disorders has been discussed since the onset of the pandemic. Four years into the pandemic, it is crucial to organize the findings and evidence accumulated thus far. The objective of this study was to review and synthesize the available scientific evidence regarding the relationship between COVID-19 and development of venous thromboembolism (VTE). A rapid systematic review was conducted by searching two electronic databases, selecting systematic review articles that assessed the association between COVID-19 and development of VTE, such as deep vein thrombosis (DVT) or pulmonary embolism (PE). The studies indicated that hospitalized COVID-19 patients are at greater risk of developing VTE, especially those admitted to intensive care units (ICUs). Elevated D-dimer levels and male gender were also associated with increased risks.

Keywords:
covid-19; SARS-CoV-2; thrombosis; venous thromboembolism; deep vein thrombosis; pulmonary embolism

Review stage	Shortcut taken	Potential impact on the study*
Data extraction	Data extracted by one investigator only	Increased number of errors. However, the impact on the results is unknown.
Literature search	Searches limited to two databases.	No impairment as long as at least two databases are used.
Inclusion criterion	Grey literature omitted.	Introduces publication bias (reduces AMSTAR2** assessment scores by 1 point).
Synthesis and analysis of data	No meta-analysis conducted; synthesis produced by just one author.	Impact unknown. Meta-analysis can increase the power and precision of the analysis. However, if conducted incorrectly, it has the potential to generate misleading results. No points are deducted in AMSTAR2 assessments if this step is eliminated because of heterogeneous studies.

Authors	Type of study	Types of studies included	Number of studies included	Date of last literature search	Results	Conclusions	AMSTAR2 score¹²
Mota et al.¹⁷	Systematic review	Cohort	6	March/2021	VTE and PE rates: One study observed that 34% of cases of VTE were identified at hospital admission and that patients who needed intensive care had higher VTE rates in both of the groups observed. Additionally, it was observed that 4.4% of the patients studied exhibited thromboembolic complications; 63% of them developed PE and 50% had VTE.	Patients with COVID-19 demonstrated a greater tendency to develop VTE and PE. In this infectious condition, in common with others, there is a generalized manifestation of inflammation and one of the main laboratory markers is increased D dimer levels, which are correlated with the severity of clinical symptoms.	Critically low
Maitra et al.¹⁸	Systematic review and meta-analysis	Cohort and RCTs	19	July/2020	Incidence of VTE: - Incidence of VTE: 23% (10-36%; 95%CI) - Incidence of PE: 12% (6-17%; 95%CI) - Incidence of DVT: 15% (8-23%; 95%CI)	It was observed that prevalence of PE and DVT was elevated among individuals with COVID-19 and that thromboembolic events in general exhibited considerable heterogeneity. This variation could be attributable to factors such as the ethnic diversity of patients, differences between screening and prophylaxis protocols, exacerbation of clinical status, and presence of comorbidities.	Critically low
Henrina et al.¹⁹	Systematic review and meta-analysis	Retrospective, prospective, and cross-sectional cohort	45	November/2020	Association between VTE and several different factors: There were significant associations between VTE and factors such as admission to an ICU (1.53-3.52; 95%CI), male sex (1.08-1.35; 95%CI), elevated D dimer (2.74-6.25; 95%CI), LDH (19.33-122.54; 95%CI), and advanced age (0.06-5.53; 95%CI).	Occurrence of VTE among patients affected by COVID-19 is directly related to a greater probability of admission to an ICU. Moreover, factors such as male sex, advanced age, and elevated white cell counts and D dimer levels are associated with a greater risk of development of VTE during the COVID-19 infection.	Critically low
Suh et al.²⁰	Systematic review and meta-analysis	Prospective and retrospective cohort	27	June/2020	Incidence of PE and DVT: - Incidence of PE: 16.5% (95%CI: I2 = 0.93) - Incidence of DVT: 14.8% (95%CI: I2 = 0.94) PE was found more frequently among patients admitted to the ICU (24.7% [95%CI]) than in those not admitted to the ICU (10.5% [95%CI]). DVT was present in 42.4% of the patients with PE.	More than half of the patients who developed PE did not present signs of concomitant DVT. The D dimer cutoffs used as criterion to rule out occurrence of PE, as defined in preexisting guidelines, appear to also be applicable to patients diagnosed with COVID-19.	Low
Kollias et al.²¹	Systematic review and meta-analysis	Observational	47	September/2020	Prevalence of PE and DVT: - Prevalence of PE: 32% (25-40%; 95%CI) - Prevalence of DVT: 27% (21-34%; 95%CI)	In patients hospitalized with COVID-19 and screened or assessed for VTE, the prevalence of DVT and PE are each approximately 30%, even applying thromboprophylaxis measures. Notably, the risk of VTE appeared to be higher in comparison with patients who did not have COVID-19 who were admitted to the same ICUs.	Critically low
Mazzaccaro et al.²²	Systematic review	Randomized clinical trials, cohort studies, and cases series	69	May/2021	Prevalence of VTE: - Prevalence of VTE: 16.7% (5.8-30%) and higher among patients in the ICU (60.8-85.4%). Advanced age, elevated D dimer, and obesity increased the chances of developing VTE. Female sex appeared to be protective against VTE.	VTE occurrence was frequently observed among patients hospitalized for COVID-19, with particularly elevated prevalence rates among patients admitted to the ICU. Factors such as advanced age, obesity, and elevated D dimer levels at admission were associated with an increased probability of VTE, whereas female sex was demonstrated as being protective against development of VTE.	Critically low
Gabbai-Armelin et al.²³	Systematic review and meta-analysis	Cross-sectional and case-control cohort.	20	Information not provided	Prognosis linked to: Hypertension and diabetes were the comorbidities most frequently associated with thrombotic events.	Individuals over the age of 60 years who had a history of hypertension, diabetes, and D dimer concentrations exceeding 3.17 μg/mL were identified as prognostic factors associated with development of COVID-19-related VTE.	Low
Roncon et al.²⁴	Systematic review and meta-analysis	Retrospective and prospective cohort	23	August/2020	Incidence of PE: - PE incidence: 14.7% (9.9-21.3%; 95%CI; I2 = 95.0%) for patients in wards and 23.4% (16.7-31.8%; 95%CI; I2 = 88.7%) for patients in an ICU.	Occurrence of PE in a hospital setting is more frequent in patients with COVID-19 who are in intensive care than among those who are in general wards. There are also indications that the number of cases of PE may be underestimated.	Critically low
Xiong et al.²⁵	Systematic review and meta-analysis	Retrospective, prospective, and case-control cohort	12	July/2020	Prevalence of thrombosis: - Prevalence of thrombosis: 22% (0.08-0.40; 95%CI) in patients in wards and 43% (0.29-0.65; 95%CI) in patients in ICUs. Compared with non-thrombotic patients, thrombotic patients exhibited higher D dimer levels. Age, platelet counts, and male sex tend to be risks.	There was a considerable prevalence of thrombosis in patients with COVID-19, especially those in ICUs, despite administration of pharmacological prophylaxis against VTE. It is therefore crucial to pay special attention to elevated D dimer levels, LDH, and leukocytes and to drops in lymphocyte levels in patients with COVID-19.	Critically low
Longchamp et al.²⁶	Systematic review and meta-analysis	Retrospective and prospective cohort	33	June/2020	Incidence of VTE and PE: - Incidence of VTE: 9% (5-13%; 95%CI) in general; 21% (14-28%; 95%CI) for patients in an ICU. - Incidence of PE: 8% (4-13%; 95%CI) in general; 17% (11-25%; 95%CI) for patients in an ICU. - Incidence of DVT: 3% (1-5%; 95%CI) in general; 8% (3-14%; 95%CI) for patients in an ICU.	There is considerable potential for severe thromboembolic events in patients hospitalized with COVID-19. However, incidence is sensitive to disease severity. These findings confirm the need to implement thromboprophylactic measures in all patients hospitalized for COVID-19, in addition to conducting clinical trials that assess different thromboprophylaxis protocols in subpopulations.	Low
Nopp et al.²⁷	Systematic review and meta-analysis	Cross-sectional and case-control cohort,	86	August/2020	Prevalence of VTE and PE: - Prevalence of VTE: 7.9% (5.1-11.2; 95%CI) in patients not in an ICU and 22.7% (18.1-27.6; 95%CI) for patients in an ICU. - Prevalence of PE: 3.5% (2.2-5.1; 95%CI) in patients not in an ICU and 13.7% (10.0-17.9; 95%CI) for patients in an ICU.	There is an elevated risk of VTE in the ICU. However, it is also high in hospitalized patients not in an ICU setting. Notably, patients who had VTE had significantly higher D dimer levels.	Low
Jenner et al.²⁸	Systematic review	Observational studies	28	November/2020	Rate of thrombotic complications: Thrombotic complications occurred in 34% of the patients treated in the ICU, with DVT reported in 16.1% and PE in 12.6%, despite anticoagulant thromboprophylaxis.	Even after administration of anticoagulant thromboprophylaxis, a considerable incidence of thrombotic complications was observed in patients with COVID-19 receiving intensive care in an ICU. Additionally, implementation of systematic screening reveals a significant number de thrombotic complications that may not be investigated on the basis of clinical suspicion alone. Systematic screening for VTE is strongly recommended.	Low
Wu et al.²⁹	Systematic review and meta-analysis	Prospective and retrospective studies	39	September/2020	Incidence of PE and VTE: Incidence of PE: 17% (13-21; 95%CI) Incidence of VTE: 42% (25-60; 95%CI) Male patients with COVID-19 have a higher probability of VTE.	VTE is frequently observed as a complication in patients severely affected by COVID-19 and is robustly related to adverse clinical outcomes.	Low
Birkeland et al.³⁰	Systematic review	Retrospective, prospective, and cross-sectional cohort	14	June/2020	Incidence of VTE: Incidence of VTE: 26.9% (20.8-33.1; 95%CI). The likelihood of VTE was greater in the ICU (OR = 6.38; 3.67-11.11; 95%CI).	Even with prior anticoagulation, the incidence of VTE was considerably elevated.	Critically low
Mansory et al.³¹	Systematic review and meta-analysis	Retrospective cohort, prospective cohort, cross-sectional, RCTs, and case series	91	December/2020	VTE epidemiology: The overall frequencies of VTE in ICU and non-ICU patients were 24.1% (20.07-28.28; 95%CI) and 7.7% (20.07-28.28; 95%CI) respectively. PE occurred in 8.5% (6.91-10.20; 95%CI) and proximal DVT occurred in 8.2% (6.67-9.87; 95%CI) of all hospitalized patients.	There is a high incidence of VTE in patients hospitalized with COVID-19, especially those in the ICU. However, sensitivity analyses indicate that previously reported rates of VTE in COVID-19 may have been overestimated.	Critically low
Porfidia et al.³²	Systematic review and meta-analysis	Cohort	30	June/2020	Incidence of VTE: - Incidence of VTE: 24% (95% PI, 5-66%) in patients in the ICU and 9% (PI 95%, 0-94%) in patients in wards. - Incidence of PE: 19% (95% PI, 6%-47%) in patients in the ICU and 4% (PI 95%, 0-100%) in patients in wards. -Incidence of DVT: 7% (95% PI, 0-69%) in patients in the ICU and 7% (95%CI, 1-49%) in patients in wards.	VTE is a common complication in patients admitted for COVID-19 and PE is a recurrent presentation. It is crucial to maintain a high level of clinical suspicion in order to identify cases promptly.	Critically low
Zhang et al.³³	Systematic review and meta-analysis	Prospective and retrospective studies	40	August/2020	Prevalence of VTE: - Prevalence of VTE: 7% in patients not in the ICU (0.01-0.18; 95%CI) and 31% in patients in the ICU (0.22-0.42; 95%CI). ICU patients also had a higher prevalence of PE, 17% (0.12-0.23; 95%CI), and a greater prevalence of DVT, 25% (0.14-0.37; 95%CI).	VTE is a frequent occurrence in patients hospitalized with COVID-19, particularly among those in the ICU. Implementation of screening tests for PE and DVT could significantly improve detection rates in patients with COVID-19, both in the ICU and in the wards, compared with tests based exclusively on clinical suspicion.	Low

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[TFN100] ^*
The potential impacts are described as per Haby et al.;¹¹

[TFN200] ^**
AMSTAR2 = Assessing the Methodological Quality of Systematic Reviews (tool for assessing the methodological quality of literature reviews).¹³