Inhaled nebulised unfractionated heparin for the treatment of hospitalised patients with COVID-19: A multicentre case series of 98 patients

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dc.contributor.authorVan Haren, Frank
dc.contributor.authorvan Loon, Lex M
dc.contributor.authorSteins, Anne
dc.contributor.authorSmoot, Thomas L
dc.contributor.authorSas, Caitlin
dc.contributor.authorStaas, Sabrina
dc.contributor.authorVilaseca, Alicia B
dc.contributor.authorBarbera, Ruben A
dc.contributor.authorVidmar, Gustavo
dc.contributor.authorBeccari, Hugo
dc.contributor.authorPopilevsky, Frida
dc.contributor.authorDaribayeva, Eleonora
dc.contributor.authorVenkatesan, Bhuvaneshwari
dc.contributor.authorMozes, Susan
dc.contributor.authorPostel, Rachel
dc.contributor.authorPopilevski, Natalie
dc.contributor.authorWebb, Andrew
dc.contributor.authorNunes, Quentin
dc.contributor.authorLaffey, John G
dc.contributor.authorArtigas, Antonio
dc.contributor.authorSmith, Roger
dc.contributor.authorDixon, Barry
dc.contributor.authorRichardson, Alice
dc.contributor.authorYoon, Hwan-Jin
dc.contributor.authorPage, Clive
dc.date.accessioned2022-12-09T05:27:10Z
dc.date.issued2022-06
dc.description.abstractAIMS 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 (FiO2 ) and FiO2 , 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/FiO2 ratio and the FiO2 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.en_AU
dc.format.mimetypeapplication/pdfen_AU
dc.identifier.issn0306-5251en_AU
dc.identifier.urihttp://hdl.handle.net/1885/281689
dc.language.isoen_AUen_AU
dc.publisherWileyen_AU
dc.rights© 2022 British Pharmacological Societyen_AU
dc.sourceBritish journal of clinical pharmacologyen_AU
dc.subjectcovid-19en_AU
dc.subjectsars-cov-2en_AU
dc.subjectcase seriesen_AU
dc.subjectinhaled heparinen_AU
dc.subjectnebulised heparinen_AU
dc.subjectpandemicen_AU
dc.subjectrespiratory failureen_AU
dc.subjectunfractionated heparinen_AU
dc.subjectanticoagulantsen_AU
dc.subjecthemorrhageen_AU
dc.subjecthumansen_AU
dc.subjectpartial thromboplastin timeen_AU
dc.subjectretrospective studiesen_AU
dc.subjectcovid-19en_AU
dc.subjectheparinen_AU
dc.titleInhaled nebulised unfractionated heparin for the treatment of hospitalised patients with COVID-19: A multicentre case series of 98 patientsen_AU
dc.typeJournal articleen_AU
dcterms.dateAccepted2021-12-27
local.bibliographicCitation.issue6en_AU
local.bibliographicCitation.lastpage2813en_AU
local.bibliographicCitation.startpage2802en_AU
local.contributor.affiliationVan Haren, F., College of Health and Medicine, The Australian National Universityen_AU
local.contributor.affiliationvan Loon, L. M., College of Health and Medicine, The Australian National Universityen_AU
local.contributor.affiliationSteins, Anne, College of Health and Medicine, The Australian National Universityen_AU
local.contributor.affiliationRichardson, A., Statistical Support Network, Australian National Universityen_AU
local.contributor.authoremailalice.richardson@anu.edu.auen_AU
local.contributor.authoruidu3767151en_AU
local.description.embargo2099-12-31
local.identifier.citationvolume88en_AU
local.identifier.doi10.1111/bcp.15212en_AU
local.identifier.essn1365-2125en_AU
local.identifier.uidSubmittedByu3767151en_AU
local.publisher.urlhttps://www.wiley.com/en-gben_AU
local.type.statusPublished Versionen_AU

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