COVID-19 Infection in Critically Ill Patients Carries a High Risk of Venous Thrombo-embolism

Abstract

Objective The coronavirus disease of 2019 (COVID-19) due to SARS-CoV-2 infection has been found to cause an increased risk for venous thromboembolism (VTE). The aims of the study were to determine the frequency of VTE in critically ill patients with COVID-19 and its correlation with D-dimer levels and pharmacological prophylaxis. Methods This was a cohort study of critically ill patients due to COVID-19. All patients admitted to the intensive care unit on the same day of April 2020 were selected, regardless of length of stay, and a single bilateral venous duplex ultrasound in the lower extremities was performed up to 72 hours later. Pulmonary embolism (PE) was diagnosed with computed tomography angiography. Asymptomatic and symptomatic VTE were registered, including pre-screening in hospital VTE. Characteristics of patients, blood test results, doses of thromboprophylaxis received, VTE events, and mortality after seven day follow up were recorded. Results A total of 230 critically ill patients were studied. Median intensive care unit stay of these patients was 12 days (interquartile range [IQR] 5 – 19 days). After seven days of follow up, the frequency of patients with VTE, both symptomatic and asymptomatic, was 26.5% (95% confidence interval [CI] 21% – 32%) (69 events in 61 patients): 45 with DVT and 16 with PE (eight of them with concomitant DVT). Cumulative frequency of symptomatic VTE was 8.3% (95% CI 4.7% – 11.8%). D-dimer values ≥ 1 500 ng/mL were diagnostic for VTE, with a sensitivity of 80% and a specificity of 42%. During follow up after screening, six patients developed new VTE. Three of them developed a recurrence after a DVT diagnosed at screening, despite receiving therapeutic doses of heparin. Mortality rates at seven day follow up were the same for those with (6.6%) and without (5.3%) VTE. Conclusion Patients with severe COVID-19 infection are at high risk for VTE, and further new symptomatic VTE events and recurrence can occur despite anticoagulation. Prophylactic anticoagulation dosage may need to be increased in patients with a low risk of bleeding.

Risk Factors for Venous Thromboembolism in Severe COVID-19: A Study-Level Meta-Analysis of 21 Studies

“…After reviewing titles and abstracts, 75 articles were selected for full text eligibility. Overall, 12 retrospective and 9 prospective studies (5296 patients) [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] were included in the meta-analysis ( Figure 1 ).…”

PICO Questions and DELPHI Methodology for the Management of Venous Thromboembolism Associated with COVID-19

“…In fact, the effect of anticoagulation in both critically and noncritically ill patients, according to the results of the corresponding mpRCT, was not influenced by stratification according to D-dimer levels [25,28]. Although cut-off levels with better sensitivity and specificity were described in a retrospective series of patients, a unanimous diagnostic cut-off point for VTE has not been defined [2,[31][32][33][34][35]. However, VTE suspicion should arise in patients with clinical deterioration associated with high D-dimer levels and no elevation of other inflammatory markers.…”

“…Consensus: 13/13 Comments: In patients with COVID-19, elevated D-dimer levels are the result of the patient's inflammatory state and hypercoagulability [2,31]. High D-dimer levels have been associated with more severe forms of the disease and with a higher risk of bleeding, VTE, and mortality [2,30,[32][33][34][35]. However, in these cases, D-dimer is not a screening test for VTE (to identify those in whom VTE should be suspected).…”

SARS-CoV-2 mechanisms of action and impact on human organism, risk factors and potential treatments. An exhaustive survey.

“…The type 1 angiotensin receptor AT1 is used by angiotensin II to increase blood pressure by inducing vasoconstriction, and to promote inflammation and fibrosis (204). Studies show that severely ill COVID-19 patients exhibit an elevated risk for venous thromboembolism even when treated with prophylactic anticoagulation drugs (205).…”