HIGH HEPARANASE LEVEL IN SURVIVORS OF COVID-19 - INDICATOR OF VASCULAR AND PULMONARY RECOVERY?
Humans
Cohort Studies
COVID-19
/ blood
Enoxaparin
Heparin
/ therapeutic use
Heparin, Low-Molecular-Weight
/ therapeutic use
Prospective Studies
Survivors
Glucuronidase
/ blood
Recovery of Function
Endothelium, Vascular
/ physiopathology
Vascular Diseases
/ diagnosis
Lung
/ physiopathology
COVID-19 Drug Treatment
Journal
Shock (Augusta, Ga.)
ISSN: 1540-0514
Titre abrégé: Shock
Pays: United States
ID NLM: 9421564
Informations de publication
Date de publication:
01 12 2022
01 12 2022
Historique:
pubmed:
23
12
2022
medline:
27
12
2022
entrez:
22
12
2022
Statut:
ppublish
Résumé
Background: Severe progression of coronavirus disease 2019 (COVID-19) causes respiratory failure and critical illness. Recently, COVID-19 has been associated with heparanase (HPSE)-induced endothelial barrier dysfunction and inflammation, so called endothelitis, and therapeutic treatment with heparin or low-molecular-weight heparin (LMWH) targeting HPSE has been postulated. Because, up to this date, clinicians are unable to measure the severity of endothelitis, which can lead to multiorgan failure and concomitant death, we investigated plasma levels of HPSE and heparin-binding protein (HBP) in COVID-19 intensive care patients to render a possible link between endothelitis and these plasma parameters. Therefore, a prospective prolonged cohort study was conducted, including 47 COVID-19 patients from the intensive care unit. Plasma levels of HPSE, and HBP were measured daily by enzyme-linked immunosorbent assay in survivors (n = 35) and nonsurvivors (n = 12) of COVID-19 from admission until discharge or death. All patients were either treated with heparin or LMWH, aiming for an activated partial thromboplastin time of ≥60 seconds or an anti-Xa level of >0.8 IU/mL using enoxaparin, depending on the clinical status of the patient (patients with extracorporeal membrane oxygenation or >0.1 μg/kg/min noradrenaline received heparin, all others enoxaparin). Results: We found significantly higher plasma levels of HPSE and HBP in survivors and nonsurvivors of COVID-19, compared with healthy controls. Still, interestingly, plasma HPSE levels were significantly higher ( P < 0.001) in survivors compared with nonsurvivors of COVID-19. In contrast, plasma HBP levels were significantly reduced ( P < 0.001) in survivors compared with nonsurvivors of COVID-19. Furthermore, when patients received heparin, they had significantly lower HPSE ( P = 2.22 e - 16) and significantly higher HBP ( P = 0.00013) plasma levels as when they received LMWH. Conclusion: Our results demonstrated that patients, who recover from COVID-19-induced vascular and pulmonary damage and were discharged from the intensive care unit, have significantly higher plasma HPSE level than patients who succumb to COVID-19. Therefore, HPSE is not suitable as marker for disease severity in COVID-19 but maybe as marker for patient's recovery. In addition, patients receiving therapeutic heparin treatment displayed significantly lower heparanse plasma level than upon therapeutic treatment with LMWH.
Identifiants
pubmed: 36548643
doi: 10.1097/SHK.0000000000002021
pii: 00024382-202212000-00007
doi:
Substances chimiques
Enoxaparin
0
heparanase
EC 3.2.1.-
Heparin
9005-49-6
Heparin, Low-Molecular-Weight
0
Glucuronidase
EC 3.2.1.31
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
514-523Informations de copyright
Copyright © 2022 by the Shock Society.
Déclaration de conflit d'intérêts
The Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy of the University Hospital Frankfurt received support from B. Braun Melsungen, CSL Behring, Fresenius Kabi, and Vifor Pharma for the implementation of Frankfurt's Patient Blood Management program, and KZ received honoraria for scientific lectures and ad board meeting within the last 3 years from CSL Behring, GE Healthcare, Edwards, Haemonetics, implatcast GmbH, med Update GmbH, Pharmacosmos, and Vifor Pharma. All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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