CHICAGO — One of the most prevalent complications in COVID-19 patients is blood clots. And now a lifetime of research on a protein that impacts clotting could hold the key to halt clots after a COVID diagnosis.
For more than 30 years, Northwestern Medicine’s Dr Douglas Vaughan has studied plasminogen activator inhibitor type 1– or PAI-1 for short. It’s a protein we naturally make in our bodies but it actually inhibits our ability to dissolve a blood clot.
“I’ve been interested in a protein that is involved in the control of the clot dissolving system in the blood for a long time,” he said. “We want our clot dissolving system to work. We have three internal systems that help keep us from clotting inside our blood vessels.”
PAI-1 blocks them all. When COVID-19 hit, Vaughan took note of a life-threatening complication, particularly among older patients, those who are overweight and people with high blood pressure or diabetes, blood clots.
“Clotting not just in the lung but in the heart, the kidney, the brain is a major contributor to trouble when somebody has COVID-19,” Vaughn said. “We think that PAI-1 is a suspicious candidate in contributing to that clotting problem that is systemic.”
To test their theory, Vaughan and his team measured the level of PAI-1 in 34 COVID-19 patients at Northwestern Memorial hospital. Their findings were off the chart.
“I’ve been measuring it for over 20 years in my lab, measured it in thousands of patients. The average level of PAI-1 in a COVID patient is 10 times normal, and we’ve seen it as high as 50 times normal in some of our patients,” Vaughn said. “I’ve never seen anything like it. It’s a pretty rational target to think about.”
Thankfully, the researchers already had a drug in the works. one that reduces PAI-1 levels by 50 to 60 percent.
“PAI-1 is increased by inflammation,” Vaughn said. “Our COVID patients are very inflamed systemically. PAI-1 is driven by low oxygen, and a lot of our COVID patients have trouble with oxygenating their blood.”
The research team was granted fast track status by the FDA and is ready to enroll patients in their drug study as early as Monday.
“I lay awake at night think about it,” Vaughn said. “Sometimes a situation finds you instead of you finding it. It created a clinical opportunity to test a hypothesis that could have a positive impact on patients hospitalized with the disease.”
The experimental drug is already in early clinical trials in Japan, where so far it appears to be safe for patients.