Randomised controlled trial comparing efficacy and safety of high versus low Low-Molecular Weight Heparin dosages in hospitalized patients with severe COVID-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation (COVID-19 HD): a structured summary of a study protocol

Vandelli, Paola; Mighali, Pasquale; Vicini, Roberto; Coluccio, Valeria; D’Amico, Roberto; Aschieri, Daniela; Brugioni, Lucio; Clini, Enrico; Codeluppi, Mauro; Imberti, Davide; Magnacavallo, Andrea; Meschiari, Marianna; Mussini, Cristina; Orlando, Sergio; Pinelli, Giovanni; Pietrangelo, Antonello; Sarti, Luca; Silva, Matteo

doi:10.1186/s13063-020-04475-z

Cited by 41 publications

(40 citation statements)

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“…In the literature there are no high-quality data yet supporting early use of LMWH at a therapeutic dose in patients with COVID-19, outside the setting of VTE treatment; randomized controlled studies evaluating this question are planned [ 23 ] or open to recruitment ( NCT04362085 , NCT04345848 , NCT04359277 ) or performed in a low number of patients [ 24 ]. In a French study conducted by Llitjos et al [ 24 ] in which there were included 26 critically ill patients with severe COVID-19 pneumonia, the anticoagulation dose (prophylactic or therapeutic) was chosen at the discretion of the treating physician based on the individual risk of thrombosis; the authors found no difference within groups, suggesting that therapeutic dose could be unjustified.…”

Section: Discussionmentioning

confidence: 99%

Venous thromboembolism and bleeding in critically ill COVID-19 patients treated with higher than standard low molecular weight heparin doses and aspirin: A call to action

Pavoni¹,

Gianesello

Pazzi³

et al. 2020

Thrombosis Research

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Background Critically ill COVID-19 patients have a clear pattern of inflammation and hypercoagulable state. The main aim of the study was to evaluate the outcome of severe COVID-19 patients basing on prothrombotic risk factors (i.e. D-dimer). We also evaluated the impact of different doses of low molecular weight heparin (LMWH) on the incidence of bleedings. Methods The data of forty-two patients admitted to the Intensive Care Unit (ICU) were retrospectively analyzed. On ICU admission, patients with D-dimer < 3000 ng/mL (Group 1) received enoxaparin 4000 UI (6000 UI, if body mass index >35) subcutaneously b.i.d. and patients with D-dimer ≥ 3000 ng/mL (Group 2) received enoxaparin 100 UI/kg every 12 h. Aspirin was administered to all patients once a day. Results Both groups presented a high incidence of perivascular thrombosis (40.9% in Group 1 and 30% in Group 2). Patients of Group 2 suffered a higher incidence of venous thromboembolism (VTE) than Group 1 (65% vs 13.6%, p = 0.001). One patient (4.5%) of Group 1 and three patients (15%) of Group 2 suffered from minor bleeding; no patient had major bleeding. Group 2 had a longer ICU and hospital stay than Group 1 (11.5 ± 5.6 vs 9.0 ± 4.8 and 30 ± 4.9 vs 21 ± 2.3, p < 0.05, respectively) as well as increased ICU mortality (25% vs 9.1%). Conclusions More severe critically ill COVID-19 patients have a high incidence of VTE and worse outcome, despite the use of heparin at the therapeutic dose. However, the use of heparin did not increase the incidence of bleeding complications.

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Section: Discussionmentioning

confidence: 99%

Venous thromboembolism and bleeding in critically ill COVID-19 patients treated with higher than standard low molecular weight heparin doses and aspirin: A call to action

Pavoni¹,

Gianesello

Pazzi³

et al. 2020

Thrombosis Research

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“…In another study, patients on prophylactic anticoagulation had higher venous thromboembolism than the therapeutic anticoagulant arm, although the latter group had a higher overall incidence of thromboembolic events, including pulmonary embolism (131). It is envisaged that these issues will be answered in ongoing clinical trials, such as the COVID-19 HD, a randomized controlled trial comparing high-dose vs. low-dose LMWH (132).…”

Section: Prophylaxis and Management Of Thromboembolism In Covid-19mentioning

confidence: 99%

Vascular Manifestations of COVID-19 – Thromboembolism and Microvascular Dysfunction

Roberts

Colley

Agbaedeng

et al. 2020

Front. Cardiovasc. Med.

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The coronavirus pandemic has reportedly infected over 31.5 million individuals and caused over 970,000 deaths worldwide (as of 22nd Sept 2020). This novel coronavirus, officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although primarily causes significant respiratory distress, can have significant deleterious effects on the cardiovascular system. Severe cases of the virus frequently result in respiratory distress requiring mechanical ventilation, often seen, but not confined to, individuals with pre-existing hypertension and cardiovascular disease, potentially due to the fact that the virus can enter the circulation via the lung alveoli. Here the virus can directly infect vascular tissues, via TMPRSS2 spike glycoprotein priming, thereby facilitating ACE-2-mediated viral entry. Clinical manifestations, such as vasculitis, have been detected in a number of vascular beds (e.g., lungs, heart, and kidneys), with thromboembolism being observed in patients suffering from severe coronavirus disease (COVID-19), suggesting the virus perturbs the vasculature, leading to vascular dysfunction. Activation of endothelial cells via the immune-mediated inflammatory response and viral infection of either endothelial cells or cells involved in endothelial homeostasis, are some of the multifaceted mechanisms potentially involved in the pathogenesis of vascular dysfunction within COVID-19 patients. In this review, we examine the evidence of vascular manifestations of SARS-CoV-2, the potential mechanism(s) of entry into vascular tissue and the contribution of endothelial cell dysfunction and cellular crosstalk in this vascular tropism of SARS-CoV-2. Moreover, we discuss the current evidence on hypercoagulability and how it relates to increased microvascular thromboembolic complications in COVID-19.

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“…Although there is a recognized association between COVID-19 and coagulopathy, and the disease score severity is positively correlated with pro-coagulant markers (e.g., high D-dimer and fibrinogen levels), accurate risk–benefit evaluations should be considered particularly in severe COVID-19 patients. Indiscriminate anticoagulants administration may increase the risk of spontaneous hemorrhage, heparin-induced thrombocytopenia (HITP) and anti-PF4-heparin complex antibodies formation [ 46 , 47 , 48 , 49 , 50 ]. Finally, in addition to the kind of heparin used for patients’ treatment (i.e., LMWH versus HMWH), individual bleeding and thrombotic risk should be considered both during hospitalization and in post-discharge COVID-19 patients [ 51 , 52 ].…”

Section: Ace1/ace2 Balancementioning

confidence: 99%

Genetic Hypothesis and Pharmacogenetics Side of Renin-Angiotensin-System in COVID-19

Gemmati

Tisato

2020

Genes

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The importance of host genetics and demography in coronavirus disease 2019 (COVID-19) is a crucial aspect of infection, prognosis and associated case fatality rate. Individual genetic landscapes can contribute to understand Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) burden and can give information on how to fight virus spreading and the associated severe acute respiratory distress syndrome (ARDS). The spread and pathogenicity of the virus have become pandemic on specific geographic areas and ethnicities. Interestingly, SARS-CoV-2 firstly emerged in East Asia and next in Europe, where it has caused higher morbidity and mortality. This is a peculiar feature of SARS-CoV-2, different from past global viral infections (i.e., SARS-1 or MERS); it shares with the previous pandemics strong age- and sex-dependent gaps in the disease outcome. The observation that the severest COVID-19 patients are more likely to have a history of hypertension, diabetes and/or cardiovascular disease and receive Renin-Angiotensin-System (RAS) inhibitor treatment raised the hypothesis that RAS-unbalancing may have a crucial role. Accordingly, we recently published a genetic hypothesis on the role of RAS-pathway genes (ACE1, rs4646994, rs1799752, rs4340, rs13447447; and ACE2, rs2285666, rs1978124, rs714205) and ABO-locus (rs495828, rs8176746) in COVID-19 prognosis, suspecting inherited genetic predispositions to be predictive of COVID-19 severity. In addition, recently, Genome-Wide Association Studies (GWAS) found COVID-19-association signals at locus 3p21.31 (rs11385942) comprising the solute carrier SLC6A20 (Na+ and Cl- coupled transporter family) and at locus 9q34.2 (rs657152) coincident with ABO-blood group (rs8176747, rs41302905, rs8176719), and interestingly, both loci are associated to RAS-pathway. Finally, ACE1 and ACE2 haplotypes seem to provide plausible explanations for why SARS-CoV-2 have affected more heavily some ethnic groups, namely people with European ancestry, than Asians.

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Randomised controlled trial comparing efficacy and safety of high versus low Low-Molecular Weight Heparin dosages in hospitalized patients with severe COVID-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation (COVID-19 HD): a structured summary of a study protocol

Cited by 41 publications

References 0 publications

Venous thromboembolism and bleeding in critically ill COVID-19 patients treated with higher than standard low molecular weight heparin doses and aspirin: A call to action

Venous thromboembolism and bleeding in critically ill COVID-19 patients treated with higher than standard low molecular weight heparin doses and aspirin: A call to action

Vascular Manifestations of COVID-19 – Thromboembolism and Microvascular Dysfunction

Genetic Hypothesis and Pharmacogenetics Side of Renin-Angiotensin-System in COVID-19

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