Fondaparinux Use in Patients With COVID-19: A Preliminary Multicenter Real-World Experience

Russo, Vincenzo; Cardillo, Giuseppe; Viggiano, G.; Mangiacapra, Sara; A, Cavalli; Fontanella, Andrea; Agrusta, Federica; Bellizzi, Annamaria; Amitrano, María; Iannuzzo, Mariateresa; Sacco, Chiara; Lodigiani, Corrado; Micco, Pierpaolo Di

doi:10.1097/fjc.0000000000000893

Cited by 27 publications

(24 citation statements)

References 12 publications

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“…9,10 LMWHs, such as enoxaparin, seem to act with a specific antithrombotic action and also with additional anti-inflammatory and antiviral activities in vitro against SARS-CoV2. 11,12 Despite the antithrombotic role of enoxaparin and also fondaparinux in preventing VTEs in COVID-19 patients,- [13][14][15] few data are available on their antithrombotic and anti-inflammatory effects in vivo. The aim of our study was to evaluate the antithrombotic and anti-inflammatory effects of fondaparinux and enoxaparin among COVID-19 patients according to selected laboratory markers found in the FONDENOXAVID study.…”

Section: Introductionmentioning

confidence: 99%

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

Cardillo¹,

Viggiano²,

Russo³

et al. 2021

JBM

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Background: 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.

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Section: Introductionmentioning

confidence: 99%

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

Cardillo¹,

Viggiano²,

Russo³

et al. 2021

JBM

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“…Moreover, the use of anticoagulant therapy with heparin has been shown to decrease mortality in hospitalized patients with severe COVID-19 [24]. LMWH or fondaparinux should be preferred over unfractionated heparin due to the decreased risk of bleeding, good predictability, dose-dependent plasma levels and longer half-life [25]. Among our study population, the experimental COVID-19 treatments, alone or in combination, were prescribed in COVID-19 patients who showed more likely concomitant comorbidities such as diabetes mellitus, hypertension and CAD; and, among them, only diabetes and hypertension have been independently associated with the administration of at least one experimental COVID-19 drug in outpatient settings.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Comorbidities and Pharmacological Treatments of COVID-19 Patients Not Requiring Hospitalization

Russo

Piccinocchi

Mandaliti

et al. 2020

IJERPH

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Introduction: The Coronavirus disease 2019 (COVID-19) outbreak is a whole Earth health emergency related to a highly pathogenic human coronavirus responsible for severe acute respiratory syndrome (SARS-CoV-2). Despite the fact that the majority of infected patients were managed in outpatient settings, little is known about the clinical characteristics of COVID-19 patients not requiring hospitalization. The aim of our study was to describe the clinical comorbidity and the pharmacological therapies of COVID-19 patients managed in outpatient settings. Materials and Methods: We performed an observational, retrospective analysis of laboratory-confirmed COVID-19 patients managed in outpatient settings in Naples, Italy between 9 March and 1 May 2020. Data were sourced from the prospectively maintained Health Search (HS)/Thales database, shared by 128 primary care physicians (PCPs) in Naples, Italy. The clinical features and pharmacological therapies of COVID-19 patients not requiring hospitalization and managed in outpatient settings have been described. Results: A total of 351 laboratory-confirmed COVID-19 patients (mean age 54 ± 17 years; 193 males) with outpatient management were evaluated. Hypertension was the most prevalent comorbidity (35%). The distribution of cardiovascular comorbidities showed no gender-related differences. A total of 201 patients (57.3%) were treated with at least one experimental drug for COVID-19. Azithromycin, alone (42.78%) or in combination (27.44%), was the most widely used experimental anti-COVID drug in outpatient settings. Low Molecular Weight Heparin and Cortisone were prescribed in 24.87% and 19.4% of the study population, respectively. At multivariate regression model, diabetes (risk ratio (RR): 3.74; 95% CI 1.05 to 13.34; p = 0.04) and hypertension (RR: 1.69; 95% CI 1.05 to 2.7; p = 0.03) were significantly associated with the experimental anti-COVID drug administration. Moreover, only diabetes (RR: 2.43; 95% CI 1.01 to 5.8; p = 0.03) was significantly associated with heparin administration. Conclusions: Our data show a high prevalence of hypertension, more likely treated with renin–angiotensin–aldosterone system (RASS) inhibitors, among COVID-19 patients not requiring hospitalization. Experimental COVID-19 therapies have been prescribed to COVID-19 patients considered at risk for increased venous thromboembolism based on concomitant comorbidities, in particular diabetes and hypertension.

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“…Consequently, the HS consumption leads to lower levels of antithrombin, creating a hypercoagulable state, endothelial injury and intracardiac thrombus formation characterizing in COVID-19 patients [110]. COVID-19 patients with hyper-coagulopathy showed a better prognosis in relation to mortality with heparin or low-molecular-weight heparin treatment [111][112][113]. HS shares high structural similarity with heparin, but their functionalities are differentiated by the interactions with various proteins, such as proteases and protease inhibitors, cytokines and their respective receptors [114].…”

Section: Heparan Sulfatementioning

confidence: 99%

The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?

et al. 2021

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The interaction between the membrane spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the transmembrane angiotensin-converting enzyme 2 (ACE2) receptor of the human epithelial host cell is the first step of infection, which has a critical role for viral pathogenesis of the current coronavirus disease-2019 (COVID-19) pandemic. Following the binding between S1 subunit and ACE2 receptor, different serine proteases, including TMPRSS2 and furin, trigger and participate in the fusion of the viral envelope with the host cell membrane. On the basis of the high virulence and pathogenicity of SARS-CoV-2, other receptors have been found involved for viral binding and invasiveness of host cells. This review comprehensively discusses the mechanisms underlying the binding of SARS-CoV2 to ACE2 and putative alternative receptors, and the role of potential co-receptors and proteases in the early stages of SARS-CoV-2 infection. Given the short therapeutic time window within which to act to avoid the devastating evolution of the disease, we focused on potential therapeutic treatments—selected mainly among repurposing drugs—able to counteract the invasive front of proteases and mild inflammatory conditions, in order to prevent severe infection. Using existing approved drugs has the advantage of rapidly proceeding to clinical trials, low cost and, consequently, immediate and worldwide availability.

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Fondaparinux Use in Patients With COVID-19: A Preliminary Multicenter Real-World Experience

Cited by 27 publications

References 12 publications

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

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

Cardiovascular Comorbidities and Pharmacological Treatments of COVID-19 Patients Not Requiring Hospitalization

The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?

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