SuPAR identifies patients at high risk of blood clot formation

Aug. 5, 2022
A study from a COVID-19 cohort reveals an additional link between the immune system and blood clots, which could improve the treatment of critical illnesses.

Blood clots are thought to occur in as many as a third of patients hospitalized with COVID-19. In many cases these clots can be deadly, such as pulmonary embolisms—blood clots that travel to the lungs. In fact, in nearly one third of patients with COVID-19, these clots led to death.

An abnormal immune response is thought to be the major driver of severe COVID-19. One protein, called soluble urokinase plasminogen activator receptor, or suPAR, circulates in the blood and originates from immune cells and has been shown to play a major role in complications of COVID-19.

Salim Hayek, M.D., Medical Director of the University of Michigan Frankel Cardiovascular Center Clinics, Shengyuan Luo, M.D., internal medicine resident physician at Rush University Medical Center and a team of researchers from around the world have been studying suPAR and its relationship to critical outcomes in COVID-19 cases.

In a publication by the International Study of Inflammation in COVID-19, a multinational observational study of patients hospitalized for COVID-19, researchers found that higher suPAR levels were associated with increased risk of blood clot formation.

Their new findings, published in the Journal of the American Heart Association, suggest that suPAR levels in hospitalized COVID patients were associated with venous thromboembolism including pulmonary embolism independently from a marker of blood clot formation called D-dimer.

The authors therefore conceived that combining suPAR, a marker of the immune system, and D-dimer could improve the reliability of determining who is at high or low risk of blood clot formation among COVID hospitalized patients.

When researchers discovered the severity of blood clots forming in COVID-19 patients early in the pandemic, they turned to suPAR for more insight. Earlier studies showed that suPAR levels were three to five times higher in COVID-19 patients and often associated with disease complications.

In the study, researchers compiled data from 1,960 adults who were hospitalized for COVID-19 and who had their suPAR levels measured at the time of admission to the hospital. All patients were monitored until they were either discharged, or in some cases, until death.

Important attributes for patients in this study included: age, sex, race, and body mass index. Additional medical conditions assessed upon admission included: diabetes, hypertension, congestive heart failure, stroke and other critical cardiology and inflammatory diseases.

Researchers measured D-dimer and suPAR levels over a 30-day period during patients’ hospitalizations and diagnosed VTE (deep vein thrombosis and pulmonary embolism) using ultrasounds of the lower extremities and scans of the lungs.

Results showed that VTE occurred in 163 patients, and of those, 65 patients developed deep vein thrombosis, 88 patients developed a pulmonary embolus, and 10 patients developed both. Patients who developed blood clots had suPAR levels nearly 50% higher than those who did not develop clots. And, when suPAR levels were combined with D-dimer, researchers could classify 41% of study participants to have low-risk for occurrence of VTE.

Now that the association is made between suPAR levels and blood clot formation, clinicians could assess who is at high or low risk, which will help them decide what therapies to use to treat them. For example, someone at high risk could be given medications before blood clot formation.

Studying suPAR and its link to the immune system has positive implications within critical COVID-19 patients, and beyond.

U of M Health release