Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID‐19
Authors: Luo Shengyuan , Vasbinder Alexi , Du‐Fay‐de‐Lavallaz Jeanne M. , Gomez Joanne Michelle D. , Suboc Tisha , Anderson Elizabeth , Tekumulla Annika , Shadid Husam , Berlin Hanna , Pan Michael , Azam Tariq U. , Khaleel Ibrahim , Padalia Kishan , Meloche Chelsea , O'Hayer Patrick , Catalan Tonimarie , Blakely Pennelope , Launius Christopher , Amadi Kingsley‐Michael , Pop‐Busui Rodica , Loosen Sven H. , Chalkias Athanasios , Tacke Frank , Giamarellos‐Bourboulis Evangelos J. , Altintas Izzet , Eugen‐Olsen Jesper , Williams Kim A. , Volgman Annabelle Santos , Reiser Jochen , Hayek Salim S. , Hayek Salim S. , Blakely Pennelope , Launius Christopher , Berlin Hanna , Amadi Kingsley , Azam Tariq U. , Shadid Husam , Pan Michael , O’Hayer Patrick , Meloche Chelsea , Feroze Rafey , Padalia Kishan J. , Anderson Elizabeth , Perry Danny , Bitar Abbas , Kaakati Rayan , Zhao Lili , Zhao Peiyao , Michaud Erinleigh , Huang Yiyuan , Catalan Toniemarie , Khaleel Ibrahim , Reiser Jochen , Samelko Beata , Hlepas Alexander , Wang Xuexiang , Patel Priya , Eugen‐Olsen Jesper , Altintas Izzet , Tingleff Jens , Stauning Marius , Houlind Morten Baltzer , Lindstrøm Mette B. , Andersen Ove , Gamst‐Jensen Hejdi , Rasmussen Line Jee Hartmann , Rasmussen Christian , Nehlin Jan O. , Kallemose Thomas , Parvaiz Imran , Giamarellos‐Bourboulis Evangelos J. , Adami Maria‐Evangelia , Solomonidi Nicky , Tsilika Maria , Saridaki Maria , Lekakis Vasileios , Loosen Sven , Luedde Tom , Keitel Verena , Chalkias Athanasios , Pantazopoulos Ioannis , Laou Eleni , Skoulakis Anargyros , Tacke Frank , Tober‐Lau Pinkus , Mohr Raphael , Kurth Florian , Sander Leif Erik , Jochum Christoph , Koehler Philipp 
Published: August 2022

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.