Inhaled nebulised unfractionated heparin for the treatment of hospitalised patients with COVID‐19: A multicentre case series of 98 patients
Frank van Haren, Lex M. van Loon, Anne Steins, Thomas Smoot, Caitlin Sas, Sabrina Staas, Alicia Vilaseca, Ruben Barbera, Gustavo Luis Vidmar, Hugo Beccari, Frida Popilevsky, Eleonora Daribayeva, Bhuvaneshwari Venkatesan, Susan Mozes, Rachel Postel, Natalie Popilevski, David J. Webb, Quentin Nunes, John G. Laffey, Antonio Artigas, Roger Smith, Barry Dixon, Alice Richardson, Hwan‐Jin Yoon, Clive Page
Abstract
Aims To determine the safety and efficacy‐potential of inhaled nebulised unfractionated heparin (UFH) in the treatment of hospitalised patients with COVID‐19. Methods Retrospective, uncontrolled multicentre single‐arm case series of hospitalised patients with laboratory‐confirmed COVID‐19, treated with inhaled nebulised UFH (5000 IU q8h, 10 000 IU q4h, or 25 000 IU q6h) for 6 ± 3 (mean ± standard deviation) days. Outcomes were activated partial thromboplastin time (APTT) before treatment (baseline) and highest‐level during treatment (peak), and adverse events including bleeding. Exploratory efficacy outcomes were oxygenation, assessed by ratio of oxygen saturation to fraction of inspired oxygen (FiO 2 ) and FiO 2 , and the World Health Organisation modified ordinal clinical scale. Results There were 98 patients included. In patients on stable prophylactic or therapeutic systemic anticoagulant therapy but not receiving therapeutic UFH infusion, APTT levels increased from baseline of 34 ± 10 seconds to a peak of 38 ± 11 seconds ( P < .0001). In 3 patients on therapeutic UFH infusion, APTT levels did not significantly increase from baseline of 72 ± 20 to a peak of 84 ± 28 seconds ( P = .17). Two patients had serious adverse events: bleeding gastric ulcer requiring transfusion and thigh haematoma; both were on therapeutic anticoagulation. Minor bleeding occurred in 16 patients, 13 of whom were on therapeutic anticoagulation. The oxygen saturation/FiO 2 ratio and the FiO 2 worsened before and improved after commencement of inhaled UFH (change in slope, P < .001). Conclusion Inhaled nebulised UFH in hospitalised patients with COVID‐19 was safe. Although statistically significant, inhaled nebulised UFH did not produce a clinically relevant increase in APTT (peak values in the normal range). Urgent randomised evaluation of nebulised UFH in patients with COVID‐19 is warranted and several studies are currently underway.