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. 2021 Jan-Feb;35(1):653-661.
doi: 10.21873/invivo.12305.

Beneficial Effects of Intermediate Dosage of Anticoagulation Treatment on the Prognosis of Hospitalized COVID-19 Patients: The ETHRA Study

Garyphallia Poulakou  1 , Evangelos Dimakakos  2 , Anastasios Kollias  1 , Konstantinos G Kyriakoulis  1 , Vasiliki Rapti  1 , Ioannis Trontzas  1 , Charalampos Thanos  1 , Mahmoud Abdelrasoul  3 , Theodora Vantana  4 , Konstantinos Leontis  1 , Eleni Kakalou  1 , Katerina Argyraki  4 , Ioannis Baraboutis  3 , Evangelos Michelakis  5 , Evangelos Giamarellos-Bourboulis  6 , Katerina Dimakou  7 , Georgios Tsoukalas  8 , Angeliki Rapti  9 , Evangelos D Michelakis  10 , Konstantinos N Syrigos  1
Affiliations

Beneficial Effects of Intermediate Dosage of Anticoagulation Treatment on the Prognosis of Hospitalized COVID-19 Patients: The ETHRA Study

Garyphallia Poulakou et al. In Vivo. 2021 Jan-Feb.

Abstract

Background/aim: To investigate the efficacy (prognosis, coagulation/inflammation biomarkers) and safety (bleeding events) of different anticoagulation dosages in COVID-19 inpatients.

Patients and methods: COVID-19 inpatients (Athens, Greece) were included. The "Enhanced dose THRomboprophylaxis in Admissions (ETHRA)" protocol was applied in certain Departments, suggesting the use of intermediate anticoagulation dosage. The primary endpoint was a composite of intubation/venous thromboembolism/death. Inflammation/coagulation parameters were assessed.

Results: Among 127 admissions, 95 fulfilled the inclusion criteria. Twenty-one events (4 deaths, 17 intubations) were observed. Regression analysis demonstrated significant reduction of events with intermediate or therapeutic dosage [HR=0.16 (95%CI=0.05-0.52) p=0.002; HR=0.17 (0.04-0.71) p=0.015, respectively]. D-Dimer values were higher in those who met the composite endpoint. Intermediate dosage treatment was associated with decreased values of ferritin. Three patients (3%) had minor hemorrhagic complications.

Conclusion: Anticoagulation treatment (particularly intermediate dosage) appears to have positive impact on COVID-19 inpatients' prognosis by inhibiting both coagulation and inflammatory cascades.

Keywords: COVID-19; anticoagulation; intermediate dosage; prognosis; thromboprophylaxis.

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Conflict of interest statement

The Authors declare no conflicts of interest related to this study.

Figures

Figure 1
Figure 1. Protocol of Enhanced dosage THRomboprophylaxis in all patients Admitted (ETHRA) for COVID-19 in medical wards. DIC: Disseminated intravascular coagulation; DVT: deep vein thrombosis; GFR: glomerular filtration rate; HIT: heparin induced thrombocytopenia; LMWH: low molecular weight heparin; PE: pulmonary embolism; q.d.: once a day
Figure 2
Figure 2. Cumulative incidence of events (VTE or intubation or death) per therapeutic anticoagulation Group
Figure 3
Figure 3. Concentrations of ferritin, interleukin-6 (IL-6) and interferongamma (IFNγ) in the circulation of seven patients before the start of treatment with LMWH and of eight patients more than 3 days after start of the treatment with LMWH. Concentrations from four patients with mild COVID-19 are provided as controls. Only significant comparisons are provided.
See this image and copyright information in PMC

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