Hyung Chun, MD: Cause of Blood Clots in COVID-19

A recent study from investigators at Yale University is diving deeper into the cause and impact of coronavirus disease 2019 (COVID-19)-associated coagulopathy.

Results of the study, which included patients treated in the ICU and non-ICU settings, indicate endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death

“While many forms of illness can generate blood clots, the endothelial cells that line the inside of blood vessels play a surprisingly large role in COVID-19 clotting,” said lead investigator Alfred Lee, MD, PhD, associate professor of medicine at Yale Cardiology Center, in a statement. “Endothelial damage is a central component in the entire spectrum of COVID-19 disease. Our study is the first to demonstrate that this process of endothelial damage is present in a wide range of COVID-19 patients, particularly as people become critically ill.”

To add to the knowledge surrounding COVID-19, investigators designed their study to assess the blood of 68 patients with COVID-19 and a group of 13 disease-free controls. Of the 68 COVID-19 patients, 48 were treated in ICUs and 20 were treated in non-ICU settings.

For the purpose of analysis, investigators sought to compare biomarkers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes between the arms.

Upon analysis, investigators found markers of endothelial cell and platelet activation were significantly elevated in patients ICU patients versus non-ICU patients—specifically, VWF antigen (mean 565% [SD, 199] vs 278% [SD, 133] ; P <.0001) and soluble P-selectin (mean 15.9 ng/mL [SD, 4.8] vs 11.2 ng/mL [SD, 3.1]; P=.0014).

Further analysis indicated mortality appeared to be significantly correlated with VWF antigen and soluble thrombomodulin in the entire study cohort. Additionally, soluble thrombomodulin concentrations above 3.26 ng/mL were associated with lower rates of discharge and a lower likelihood of survival (HR, 5.9; 95% CI, 1.9-18.4; P=.0087).

To learn more about the risks and impact of blood clots in COVID-19 patients, Practical Cardiology® invited study investigator Hyung Chun, MD, associate professor of medicine and pathology at Yale School of Medicine and director of Translational Research in the Yale Pulmonary Vascular Disease Program, to take part in an interview discussing his study.

This study, “Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study,” was published in The Lancet Haematology.