Risk of deep vein thrombosis and pulmonary embolism in patients with COVID-19

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In a systematic review of the worldwide published data, Cihan Ay, Stephan Nopp, and Florian Moik from the department of medicine I, clinical division of haematology and haemostaseology, at the Medical University of Vienna, now for the first time provide an in-depth analysis of the risk of venous thrombo-embolism (VTE) in patients hospitalised for COVID-19. While hospitalised patients at general wards have a VTE risk of between 5 and 11%, the risk of developing deep vein thrombosis or pulmonary embolism in critically ill patients is 18 to 28%.

“From the beginning of the COVID-19 pandemic, studies reported an increased rate of thrombosis and pulmonary embolism in patients with COVID-19. On the basis of these reports, but without robust evidence from controlled interventional studies, global treatment strategies were developed, recommending more intense thrombo-prophylaxis strategies. Our study now offers a better understanding of the underlying risk and, therefore, aids in individual treatment decisions based on accurate risk assessment for the different patient groups,” reports principal investigator Ay.

Within their review of the literature, the authors assessed a total of 5,951 studies published in the field of VTE in COVID-19. Of those, 86 studies were found eligible for inclusion and reported rates of thrombosis and pulmonary embolism in COVID-19 patients. After excluding additional studies due to underlying risk of bias in a structured assessment, 66 studies (28,173 patients) were found eligible to perform a meta-analysis to provide a robust estimate on risk of VTE in COVID-19.

The main findings are as follows: the overall VTE risk in hospitalised patients with COVID-19 is 14%, despite rigorous thrombo-prophylaxis regimens in most studies.

Further, high heterogeneity in VTE rates was found between different patient subgroups. The rate was highest in patients admitted to intensive care units, with 23% of patients suffering VTE. Patients admitted to general wards suffered VTE in 8% of the cases. These findings underline the high risk of VTE in COVID-19 patients.

In addition, the authors specifically focused on estimating the risk of potentially life-threatening pulmonary embolism. The result: “This risk is considerably higher than in other comparable serious medical illnesses and ranges between 10 and 18% in COVID-19 patients requiring intensive care. Further, astonishingly, deep vein thrombosis was detected in almost half of the hospitalised COVID-19 patients who had been systematically screened for thrombosis using ultrasound.”

These findings underscore the strong impact of COVID-19 on the blood-clotting system. In addition, an exploratory analysis revealed that patients who developed deep vein thrombosis or pulmonary embolism during hospitalisation had significantly higher D-dimer concentrations at admission, a laboratory parameter that indicates an activated coagulation system. This finding might be used to help develop personalized, risk-stratified thrombo-prophylaxis strategies in the future.

In summary, the authors provide a detailed evaluation of the risk of VTE based on the severity of the disease. Future studies need to determine whether elevated D-dimer at hospital admission justifies intensification of anticoagulant treatment in hospitalised patients with COVID-19.

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 COVID‐19 patients.
Methods: We conducted a systematic literature search (MEDLINE, EMBASE, WHO COVID‐19 database) to identify studies reporting VTE‐rates in COVID‐19 patients. 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% men, 20% ICU‐patients) were included in quantitative analysis. The overall VTE‐prevalence estimate was 14.1% (95%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.

Authors
Stephan Nopp, Florian Moik, Bernd Jilma, Ingrid Pabinger, Cihan Ay

 

Medical University of Vienna material

 

Research and Practice in Thrombosis and Haemostasis abstract

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