OC 22.2 - Effect of different anticoagulation doses on biomarkers of inflammation and glycocalyx in severe COVID-19 patients

Sunday, June 23, 2024

15:00 – 15:15 ICT

Room: Ballroom B2

Presenting Author(s)

Marc Blondon, MD MS

Senior physician
Division of Angiology and Hemostasis, Geneva University Hospitals
Geneve, Geneve, Switzerland

Co-Author(s)

SG

Serge Grazioli

Senior physician
Division of pediatric intensive care unit, Geneva University Hospitals
Geneva, Geneve, Switzerland
CC

Christophe Combescure

Biostatistician
Geneva University Hospitals and Faculty of Medicine
Geneva, Geneve, Switzerland
SP

Sabrina Pagano

Biologist
Division of Laboratory medicine, Geneva University Hospitals
Geneva, Geneve, Switzerland
NV

Nicolas Vuilleumier

Professor
Division of Laboratory medicine, Geneva University Hospitals
Geneva, Geneve, Switzerland
CM

Christophe Marti

Senior physician
Division of General Internal Medicine, Geneva University Hospitals
Geneva, Geneve, Switzerland
Helia Robert-Ebadi

Staff physician vascular medicine
Geneva University Hospitals and Faculty of Medicine
Geneva, Geneve, Switzerland
Marc Righini

Head of the Division of Angiology and Hemostasis
Geneva University Hospitals and Faculty of Medicine
Geneva, Geneve, Switzerland
Pierre Fontana

Professor
Division of Angiology and Hemostasis, Geneva University Hospitals
Genève, Geneve, Switzerland
Alessandro Casini, MD

Senior physician
Division of Angiology and Hemostasis, Geneva University Hospitals
Geneva, Geneve, Switzerland

Background: Therapeutic heparins may improve the prognosis of patients hospitalized for severe COVID-19, but the precise mechanisms remain unclear.

Aims: Our aim was to explore the effect of therapeutic dose heparins, compared with lower dose, on markers of coagulation, inflammation and glycocalyx shedding.

Methods: The COVID-HEP clinical trial randomized inpatients with severe COVID-19 to therapeutic anticoagulation or to intermediate-dose anticoagulation (critical inpatients) / low-dose anticoagulation (non-critical inpatients). A subgroup of 85 participants had blood drawn at baseline (t0) and at a median 5 days later (t1). We recorded levels of D-dimer, fibrinogen and C-reactive protein from routine laboratories and measured levels of IL-1, IL-6, IL-8, TNF-alpha and syndecan-1 on frozen samples. We compared the change of geometric means between randomization arms, with adjustment for disease severity and tocilizumab.

Results: Among 85 participants, 39 were randomized to high-dose anticoagulation (19 critical and 20 non-critical) vs. 46 to intermediate-dose (27 critical) or to low-dose anticoagulation (19 non-critical). Median levels of biomarkers (IQR) and their differential changes are found in Table 1. From baseline until t1, we observed a significant increase in levels of syndecan-1 and decreases in levels of D-dimer, fibrinogen and C-reactive protein, in both randomization arms. Compared with low/intermediate-dose anticoagulation, high-dose anticoagulation decreased levels of D-dimer further, with a relative -31.1% supplemental decrease (95%CI -51.8 to -1.6) and increased levels of Syndecan-1 further, with a relative +51.3% supplemental increase (95%CI +18.1 to +94.0). Levels of other biomarkers were not differentially modified by the dose of anticoagulation.

Conclusion(s): Among severe COVID-19 inpatients, therapeutic anticoagulation, compared with lower-dose anticoagulation, decreased levels of D-dimer, but did not modify levels of inflammatory cytokines. Contrary to our hypothesis, it increased levels of syndecan-1, a marker of glycocalyx shedding. These ex-vivo randomized findings do not support a beneficial effect of high-dose heparins on the immune response or protection of glycocalyx.