Study may offer insights into novel therapeutic strategies to treat COVID-19 related blood clots

Blood clots or thromboembolic complications in patients with COVID-19 are associated with increased levels of various proteins that cause blood to clot, compared with people with blood clots unrelated to COVID-19, according to a small study by Yale Cancer Center researchers. These findings may offer insights into novel therapeutic strategies to treat patients with COVID-19 related blood clots. The findings were reported today at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition in Atlanta, Georgia.

We expected to find differences in protein levels in patients who developed blood clots in the presence of COVID-19 and without it. However, the absence of significant differences in protein levels of patients with COVID-19 with and without blood clots was unexpected and suggests that the overall difference in concentration of proteins involved in the body's ability to clot blood is related to the COVID-19 disease itself."

Daria Madeeva, MD, lead study author, physician, Yale New Haven Health

Between December 2020 and February 2021, blood was collected from 48 inpatients. Of these, 24 patients had a confirmed diagnosis of COVID-19 infection and an arterial or venous thromboembolism; 17 had a COVID-19 infection with no arterial thrombosis and absence of venous thromboembolism, while 7 were diagnosed with an arterial or venous thromboembolism in the absence of COVID-19. Researchers found that levels of several proteins were higher in patients with COVID-19 who also developed blood clots. One of these proteins, tissue factor, is classically associated with an injury to the lining of the vessel (endothelium), and since it was higher in blood of patients with COVID-19, it suggests a more profound injury to the endothelium. The level of another protein, pentraxin-3, was also higher in the patients who developed blood clots in the setting of COVID-19. This protein is produced by endothelial cells during inflammation, and therefore also a marker of endothelial injury. Researchers also found that two additional proteins, C2 and C5a also higher in patients who developed blood clots in the setting of COVID-19, as well as lipocalin-2 and resistin. Prior studies have noted, these proteins are markers of neutrophil activation in patients with COVID-19, and their higher levels are associated with more severe disease. Additionally, levels of proteins SAA and PECAM-1 were also higher in patients who developed blood clots with COVID-19.

"Moving forward, we would like to evaluate a much greater number of proteins and include more patients in our studies," said Alexander B Pine, MD, PhD, Assistant Professor of Medicine (Hematology) at Yale Cancer Center and senior author of the study. "Also, a similar proteomics approach could be applied to evaluate mechanisms and factors contributing to the development of thrombosis in inflammatory diseases other than COVID-19."

Other Yale authors on the study include Kelly Borges, Marcus Shallow, Prerak Juthani, Stephen Wang, MD MPH, Akash Gupta, MD, Hyung Chun, MD, and Alfred Lee, MD, PhD.

This research was supported in part by a pilot grant from the DeLuca Center for Innovation in Hematology Research.