Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID‐19
Shengyuan Luo, Alexi Vasbinder, Jeanne du Fay de Lavallaz, Joanne Michelle D. Gomez, Tisha Suboc, Élizabeth Anderson, Annika Tekumulla, Husam Shadid, Hanna Berlin, Michael Pan, Tariq U. Azam, Ibrahim Khaleel, Kishan Padalia, Chelsea Meloche, Patrick O’Hayer, Tonimarie Catalan, Pennelope Blakely, Christopher Launius, Kingsley‐Michael Amadi, Rodica Pop‐Busui, Sven H. Loosen, Athanasios Chalkias, Frank Tacke, Evangelos J. Giamarellos‐Bourboulis, Izzet Altintas, Jesper Eugen‐Olsen, Kim A. Williams, Annabelle Santos Volgman, Jochen Reiser, Salim S. Hayek, Salim S. Hayek, Pennelope Blakely, Christopher Launius, Hanna Berlin, Kingsley Amadi, Tariq U. Azam, Husam Shadid, Michael Pan, Patrick O’Hayer, Chelsea Meloche, Rafey Feroze, Kishan Padalia, Élizabeth Anderson, Danny Perry, Abbas Bitar, Rayan Kaakati, Lili Zhao, Peiyao Zhao, Erinleigh Michaud, Yiyuan Huang, Toniemarie Catalan, Ibrahim Khaleel, Jochen Reiser, Beata Samelko, Alexander Hlepas, Xuexiang Wang, Priya Patel, Jesper Eugen‐Olsen, Izzet Altintas, Jens Tingleff, Marius Ahm Stauning, Morten Baltzer Houlind, Mette Bendtz Lindstrøm, Ove Andersen, Hejdi Gamst‐Jensen, Line Jee Hartmann Rasmussen, Christian Rasmussen, Jan O. Nehlin, Thomas Kallemose, Imran Parvaiz, Evangelos J. Giamarellos‐Bourboulis, Maria‐Evangelia Adami, Nicky Solomonidi, Μαρία Τσιλικά, Maria Saridaki, Vasileios Lekakis, Sven H. Loosen, Tom Luedde, Verena Keitel, Athanasios Chalkias, Ioannis Pantazopoulos, Eleni Laou, Anargyros Skoulakis, Frank Tacke, Pinkus Tober‐Lau, Raphael Mohr, Florian Kurth, Leif Erik Sander, Christoph Jochum, Philipp Koehler
Abstract
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 (β=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. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04818866.