Antithrombotic and Anti-Inflammatory Effects of Fondaparinux and Enoxaparin in Hospitalized COVID-19 Patients: The FONDENOXAVID Study

Abstract

Giuseppe Cardillo,1 Giuseppe Vito Viggiano,2 Vincenzo Russo,3 Sara Mangiacapra,4 Antonella Cavalli,5 Giampiero Castaldo,2 Federica Agrusta,2 Annamaria Bellizzi Snr,5 Maria Amitrano Snr,4 Mariateresa Iannuzzo,6 Clara Sacco,7 Corrado Lodigiani,7 Andrea Fontanella,6 Pierpaolo Di Micco6 For The FondenoxavidStudy Group1Medylab, Biochimica Avanzata Laboratory, Naples, Italy; 2UO Pronto Soccorso e Medicina D’urgenza, Semintensiva Covid, Ospedale Ramazzini Di Carpi — AUSL Modena, Modena, Italy; 3Department of Translational Medical Sciences, University of Campania Luigi Vanvitelli Monaldi Hospital, Piazzale Ettore Ruggeri, Naples 80131, Italy; 4UOC Medicina, AO Moscati, Avellino, Italy; 5UOC Medicina-Covid, Presidio Opsedaliero Frangipane Di ArianoIrpino (AV), Naples, Italy; 6UOC Medicina, Ospedale Fatebenefratelli di Napoli, Naples, Italy; 7Humanitas Clinical and Research Center IRCCS, Rozzano, ItalyCorrespondence: Pierpaolo Di Micco Email [email protected]: Since the outbreak of novel coronavirus SARS-CoV2 around the world, great attention has been paid to the effects of such antithrombotic drugs as heparinoids, because they have antiviral action in vitro and antithrombotic actions in vivo. We conducted a retrospective analysis in inpatients with confirmed COVID-19 on the anti-inflammatory and antithrombotic effects of enoxaparin and fondaparinux at prophylactic doses.Methods: This retrospective cohort study used patients with confirmed COVID-19 during the first months of the Italian outbreak from February 18 to April 30, 2020. Our aim was to compare clinical characteristics, prophylactic treatment, markers of inflammation, and thrombotic outcomes in inpatients positive for SARS-CoV2 during hospitalization associated with thromboprophylaxis with enoxaparin (40 mg or 60 mg once daily) or fondaparinux (2.5 mg once daily). Statistical analysis was conducted with using MatLab R2016B and ad hoc functions.Results: There were no significatant differences in clinical characteristics between patients that used enoxaparin or fondaparinux as thromboprophylaxis for SARS-CoV2. No differences were found in D-dimer and fibrinogen levels either, which were used as markers of inflammation during the infection at testing on admission and after 3 weeks.Significant differences in CRP, IL6, and LDH were found in patients after 21 days’ treatment.Discussion: Increased levels of fibrinogen and D-dimer in patients with confirmed COVID-19 have been reported in several studies. Our results showed that anti-inflammatory effects of fondaparinux and enoxaparin after 3 weeks of prophylactic treatment were similar when levels of fibrinogen and D-dimer were considered. Furthermore, levels of CRP showed a decrease in patients treated with enoxaparin and fondaparinux, although the decrease in the fondaparinux group seems to be more relevant.Keywords: venous thromboembolism, fibrinogen, D-dimer, COVID-19, SARS-CoV2, fondaparinux, enoxaparin

Keywords

• venous thromboembolism
• fibrinogen
• d-dimer
• covid-19
• sars-cov-2
• fondaparinux
• enoxaparin