4.6 Article

Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID-19

Journal

JOURNAL OF THE AMERICAN HEART ASSOCIATION
Volume 11, Issue 18, Pages -

Publisher

WILEY
DOI: 10.1161/JAHA.122.025198

Keywords

COVID-19; soluble urokinase plasminogen activator receptor; thromboembolism

Funding

  1. National Heart, Lung, and Blood Institute-funded postdoctoral fellowship [T32HL007853]
  2. National Heart, Lung, and Blood Institute [1R01HL153384-01]
  3. National Institute of Diabetes and Digestive and Kidney Diseases [1R01DK12801201A1, U01-DK119083-03S1]
  4. Hellenic Institute for the Study of Sepsis
  5. Charite Universitaetsmedizin Berlin
  6. Berlin Institute of Health
  7. Frankel Cardiovascular Center COVID-19: Impact Research Ignitor [U-M G024231]

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Higher levels of soluble urokinase plasminogen activator receptor (suPAR) were found to be independently associated with an increased risk of venous thromboembolism (VTE) in COVID-19 hospitalized patients, regardless of D-dimer levels. Combining suPAR and D-dimer can help identify patients at low risk of developing VTE.
BACKGROUND: Venous thromboembolism (VTE) contributes significantly to COVID-19 morbidity and mortality. The urokinase receptor system is involved in the regulation of coagulation. Levels of soluble urokinase plasminogen activator receptor (suPAR) reflect hyperinflammation and are strongly predictive of outcomes in COVID-19. Whether suPAR levels identify patients with COVID-19 at risk for VTE is unclear. METHODS AND RESULTS: We leveraged a multinational observational study of patients hospitalized for COVID-19 with suPAR and D-dimer levels measured on admission. In 1960 patients (mean age, 58 years; 57% men; 20% Black race), we assessed the association between suPAR and incident VTE (defined as pulmonary embolism or deep vein thrombosis) using logistic regression and Fine-Gray modeling, accounting for the competing risk of death. VTE occurred in 163 (8%) patients and was associated with higher suPAR and D-dimer levels. There was a positive association between suPAR and D-dimer (beta=7.34; P=0.002). Adjusted for clinical covariables, including D-dimer, the odds of VTE were 168% higher comparing the third with first suPAR tertiles (adjusted odds ratio, 2.68 [95% CI, 1.51-4.75]; P<0.001). Findings were consistent when stratified by D-dimer levels and in survival analysis accounting for death as a competing risk. On the basis of predicted probabilities from random forest, a decision tree found the combined D-dimer <1 mg/L and suPAR <11 ng/mL cutoffs, identifying 41% of patients with only 3.6% VTE probability. CONCLUSIONS: Higher suPAR was associated with incident VTE independently of D-dimer in patients hospitalized for COVID-19. Combining suPAR and D-dimer identified patients at low VTE risk.

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