Abstract Number: PB0159
Meeting: ISTH 2021 Congress
Background: Since January 2020, the SARS-CoV-2 pandemic has caused ~500,000 deaths in the United States alone. Many fatalities result from thrombotic events such as stroke, pulmonary embolism, or heart attack secondary to disseminated intravascular coagulation. Clinicians use anticoagulant and antiplatelet therapies to mitigate the risk of clotting, but these therapies increase the likelihood of bleeding. We propose that a decrease in activity of the anticoagulant Protein S (PS) significantly increases thrombotic risk in individuals with COVID-19.
Aims: Determine whether deficiency or modification of PS in hospitalized COVID-19 patients increases the risk of venous thromboembolism.
Methods: The Ochsner Clinical Foundation and Louisiana State University Health Sciences Center Biorepository provided plasma samples from hospitalized patients who tested positive for SARS-CoV-2. To measure the amounts of bound and free PS, thrombomodulin, and PA1, we performed ELISA, immunoblot, and thrombin generation assays.
ELISA data showed that free PS was deficient in severe COVID-19 patients (Figure 1A); bound PS was in the normal range (data not shown). We observed a significant rise in peak thrombin with most hospitalized patient samples, and thrombin generation reverted to control level by addition of free PS. However, addition of thrombomodulin did not have a significant similar effect (Figure 1B). Immunoblots (probed with PS antibodies) of hospitalized samples (low free PS; Figure 2) and controls (average is shown) revealed a significant decrease in PS amount (determined by densitometry) of the hospitalized samples compared with control samples. We immunoprecipitated PS from hospitalized and control samples to assess the presence of post translational modifications in Protein S that might cause a decrease in free PS. These samples are being analyzed by mass spectrometry.
To cite this abstract in AMA style:Nguyen T, Melancon D, Dean M, Zea A, Chatterjee S, Harman J, Pilli V, Nossaman R, Ochoa J, Ochoa A, Majumder R. Altered Protein S Activity Contributes Significantly to COVID-19 Pro-thrombotic State [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/altered-protein-s-activity-contributes-significantly-to-covid-19-pro-thrombotic-state/. Accessed December 8, 2021.
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