The Middletown Press (Middletown, CT)
Predictor of fatal clots in COVID victims identified
Protein high in sickest intensive care unit patients
Originally seen as a respiratory illness, the disease caused by the novel coronavirus, SARS-CoV-2, has been found to cause unusual symptoms, including blood clots, a loss of taste and smell and an inflammatory syndrome in children.
The blood clots even have been found to occur in tiny capillaries, which is unusual, according to Dr. Gary Gibbons, director of the National Institutes of Health’s Heart, Lung, and Blood Institute. Clotting can cause strokes as well as damage to lungs, kidneys and other organs.
Dr. Alfred Lee and Dr. Hyung Chun of the Yale
School of Medicine were among 23 Yale authors of a study published in the journal The Lancet Haematology. The study found a biomarker in patients’ blood that can predict which patients are most likely to develop the potentially fatal clotting.
“In the sickest patients who were in the intensive care unit, these markers were particularly high,” Lee said.
Blood clotting, essential when there is an injury to a blood vessel, largely is controlled by cells in the veins, arteries and capillaries, Lee said. “The blood vessels themselves are sort of the anchors on which blood clotting happens,” he said.
The vessels are lined with endothelial cells, which, among other functions, produce a protein called thrombomodulin. The protein suppresses blood clotting in normal circumstances, limiting it to the site of the injury to the blood vessel. But the researchers found that patients with severe COVID-19 had high levels of thrombomodulin.
“It could be the cells are activated somehow … or there could be cell death,” Chun said. “We were treating this as a marker of disease severity … and a marker of blood vessel injury.”
“We found patients that have higher levels of thrombomodulin in their blood were more likely to die of COVID-19,” he said.
While thrombomodulin normally keeps blood clotting in check, the release of high amounts of it may come too late in the disease, when clotting has already begun, Lee said.
The protein is a biomarker to see how badly endothelial cells are injured, which in turn can help predict how likely a patient is to die of COVID, the doctors said. Similar reactions have been found in patients with sepsis, a total body infection.
“The higher the endothelial injury, the higher, the thrombomodulin, the more likely to die,” Lee said.
The study involved testing the blood of 68 patients with COVID-19. Forty-eight of them were critically ill and in an intensive care unit; 20 were in non-ICU beds. Thirteen people without COVID were used as a control group. Researchers found that markers for endothelial cell and blood platelet activation were about twice as high in the critically ill patients as in the less-sick patients. The COVID patients who were not in the ICU also had higher levels than in the control group.
“Now we think there is an important blood test that can be developed to prognosticate how sick these patients may become,” Chun said.
Researchers also can develop ways to mitigate the injury to blood vessels, he said.
“We have reached out to a number of companies that make these diagnostic blood tests. … A couple of companies are interested,” Chun said.
“By applying therapies that can protect the blood vessels, as an indirect consequence of that you may see lower levels of thrombomodulin in the blood,” he said.
One possible treatment may be dipyridamole, an oral medication used to prevent stroke, according to a press release.