Antithrombin Activity Is Associated with Persistent Thromboinflammation and Mortality in Patients with Severe COVID-19 Illness

Abstract

Background: Severe COVID-19 illness can lead to thrombotic complications, organ failure, and death. Antithrombin (AT) regulates thromboinflammation and is a key component of chemical thromboprophylaxis. Our goal was to examine the link between AT activity and responsiveness to thromboprophylaxis, markers of hypercoagulability, and inflammation among severe COVID-19 patients. Methods: A single-center, prospective observational study enrolling SARS-CoV-2 positive patients admitted to the intensive care unit on prophylactic enoxaparin. Blood was collected daily for 7 days to assess AT activity and anti-FXa levels. Patient demographics, outcomes, and hospital laboratory results were collected. Continuous variables were compared using Mann-Whitney tests, and categorical variables were compared using Chi-square tests. Multivariable logistic regression was used to determine the association between AT activity and mortality. Results: In 36 patients, 3 thromboembolic events occurred, and 18 (50%) patients died. Patients who died had higher fibrinogen, D-dimer, and C-reactive protein (CRP) levels and lower AT activity. Reduced AT activity was independently associated with mortality and correlated with both markers of hypercoagulability (D-dimer) and inflammation (CRP). Conclusions: Low AT activity is associated with mortality and persistent hypercoagulable and proinflammatory states in severe COVID-19 patients. The anti-thromboinflammatory properties of AT make it an appealing therapeutic target for future studies.

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“…Antithrombin (AT) is the most important anticoagulant in plasma and tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor (PAI) is also paly an important role in the fibrinolytic system. The activity of AT is significantly decreased when patients are accompanied by obesity and other risk factors [ 13 – 15 ]. The possible mechanism of higher BMI would increase incidence of DVT is that the level of PAI would increase and activity of t-PA decrease significantly in overweight and obesity patients, which suggesting that fibrinolytic function may compromise with the advanced BMI.…”