Intensified thromboprophylaxis in COVID-19 critically ill patients: Is it enough?
Ontology highlight
ABSTRACT:
SUBMITTER: de Montmollin E
PROVIDER: S-EPMC7862021 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Background Patients with severe SARS-CoV-2 infection have been shown to have abnormal coagulation parameters and are at increased risk of thromboembolism. The optimal thromboprophylaxis regimen that minimizes thrombosis without increased risk of serious bleeding is uncertain. Objectives To describe the efficacy and safety of increased intensity (enhanced) thromboprophylaxis in patients with COVID-19 admitted to the medical intensive care unit (MICU). Methods This is a retrospective cohort analysis of patients with a diagnosis of COVID-19 admitted to the MICU of an urban safety net hospital. With the exception of patients being supported with extracorporeal membrane oxygenation or on chronic anticoagulation who received therapeutic dosing of anticoagulation, thromboprophylaxis was given as either enoxaparin or unfractionated heparin in doses higher than those recommended for standard prophylaxis, but lower than those used for therapeutic anticoagulation. Main results Of the 120 patients managed with an enhanced thromboprophylaxis protocol, 6 (5%) experienced thromboembolism as a result of their COVID-19 disease (1 pulmonary embolus, 4 deep vein thromboses, and 1 arterial embolism). Four patients experienced major bleeding while receiving therapeutic anticoagulation. Conclusions In critically ill patients with COVID-19, increased intensity (enhanced) thromboprophylaxis appears to be effective at preventing clinically significant thromboembolic events without an increased risk of serious bleeding.
| S-EPMC8019488 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-02-28 | GSE197259 | GEO
Project description:BackgroundA substantial proportion of critically ill COVID-19 patients develop thromboembolic complications, but it is unclear whether higher doses of thromboprophylaxis are associated with lower mortality rates. The purpose of the study was to evaluate the association between initial dosing strategy of thromboprophylaxis in critically ill COVID-19 patients and the risk of death, thromboembolism, and bleeding.MethodIn this retrospective study, all critically ill COVID-19 patients admitted to two intensive care units in March and April 2020 were eligible. Patients were categorized into three groups according to initial daily dose of thromboprophylaxis: low (2500-4500 IU tinzaparin or 2500-5000 IU dalteparin), medium (> 4500 IU but < 175 IU/kilogram, kg, of body weight tinzaparin or > 5000 IU but < 200 IU/kg of body weight dalteparin), and high dose (≥ 175 IU/kg of body weight tinzaparin or ≥ 200 IU/kg of body weight dalteparin). Thromboprophylaxis dosage was based on local standardized recommendations, not on degree of critical illness or risk of thrombosis. Cox proportional hazards regression was used to estimate hazard ratios with corresponding 95% confidence intervals of death within 28 days from ICU admission. Multivariable models were adjusted for sex, age, body mass index, Simplified Acute Physiology Score III, invasive respiratory support, and initial dosing strategy of thromboprophylaxis.ResultsA total of 152 patients were included: 67 received low-, 48 medium-, and 37 high-dose thromboprophylaxis. Baseline characteristics did not differ between groups. For patients who received high-dose prophylaxis, mortality was lower (13.5%) compared to those who received medium dose (25.0%) or low dose (38.8%), p = 0.02. The hazard ratio of death was 0.33 (95% confidence intervals 0.13-0.87) among those who received high dose, and 0.88 (95% confidence intervals 0.43-1.83) among those who received medium dose, as compared to those who received low-dose thromboprophylaxis. There were fewer thromboembolic events in the high (2.7%) vs medium (18.8%) and low-dose thromboprophylaxis (17.9%) groups, p = 0.04.ConclusionsAmong critically ill COVID-19 patients with respiratory failure, high-dose thromboprophylaxis was associated with a lower risk of death and a lower cumulative incidence of thromboembolic events compared with lower doses.Trial registrationClinicaltrials.gov NCT04412304 June 2, 2020, retrospectively registered.
| S-EPMC7680989 | biostudies-literature
Project description:Infections caused by SARS-CoV-2 may cause a severe disease, termed COVID-19, with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms, and their modulation is the only therapeutic strategy that has shown a mortality benefit. Herein, we used peripheral blood transcriptomes of critically-ill COVID-19 patients obtained at admission in an Intensive Care Unit, to identify two clusters that, in spite of no major clinical differences, have different gene expression profiles that reveal different underlying pathogenetic mechanisms and ultimately have different ICU outcome. A transcriptomic signature was used to identify these clusters in an external validation cohort, yielding a similar result. These results illustrate the potential of transcriptomic profiles to identify patient endotypes and point to relevant pathogenetic mechanisms in COVID-19.
2023-04-29 | GSE206264 | GEO
Project description:Infections caused by SARS-CoV-2 may cause a severe disease, termed COVID-19, with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms, and their modulation is the only therapeutic strategy that has shown a mortality benefit. Herein, we used peripheral blood transcriptomes of critically-ill COVID-19 patients obtained at admission in an Intensive Care Unit, to identify two clusters that, in spite of no major clinical differences, have different gene expression profiles that reveal different underlying pathogenetic mechanisms and ultimately have different ICU outcome. A transcriptomic signature was used to identify these clusters in an external validation cohort, yielding a similar result. These results illustrate the potential of transcriptomic profiles to identify patient endotypes and point to relevant pathogenetic mechanisms in COVID-19.
2022-02-28 | GSE197258 | GEO
Project description:Infections caused by SARS-CoV-2 may cause a severe disease, termed COVID-19, with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms, and their modulation is the only therapeutic strategy that has shown a mortality benefit. Herein, we used peripheral blood transcriptomes of critically-ill COVID-19 patients obtained at admission in an Intensive Care Unit, to identify two clusters that, in spite of no major clinical differences, have different gene expression profiles that reveal different underlying pathogenetic mechanisms and ultimately have different ICU outcome. A transcriptomic signature was used to identify these clusters in an external validation cohort, yielding a similar result. These results illustrate the potential of transcriptomic profiles to identify patient endotypes and point to relevant pathogenetic mechanisms in COVID-19.
2022-02-28 | GSE197204 | GEO
Project description:Single-cell RNA-sequencing reveals a shift from focused IFN alpha-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 – a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.
2021-06-18 | GSE178404 | GEO
Project description:The reported incidence rate of venous and arterial thrombotic events in critically ill patients with COVID-19 infections is high, ranging from 20% to 60%. We adopted a patient-tailored thromboprophylaxis protocol based on clinical and laboratory presentations for these patients in our institution. We hypothesised that patients who received high-intensity thromboprophylaxis treatment would experience fewer thrombotic events. The aims of our study were to explore the incidence of thrombotic events in this population; to assess independent factors associated with thrombotic events and to evaluate the incidence of haemorrhagic events. A retrospective review of all adult patients with confirmed SARS-CoV-2 infection admitted to the intensive care unit (ICU) between 1 March and 29 May 2020 was performed. The primary outcome was a composite of venous and arterial thrombotic events diagnosed during the ICU stay. Multivariable logistic regression was used to identify the independent factors associated with thrombotic events. A total of 188 patients met the inclusion criteria. All received some type of thromboprophylaxis treatment except for six patients who did not receive any prophylaxis. Of the 182 patients who received thromboprophylaxis, 75 (40%) received high-intensity thromboprophylaxis and 24 (12.8%) were treated with therapeutic anticoagulation. Twenty-one patients (11.2%) experienced 23 thrombotic events (incidence rate of 12.2% (95%CI 7.9-17.8)), including 12 deep venous thromboses, 9 pulmonary emboli and 2 peripheral arterial thromboses. The multivariable logistic regression analysis showed that only D-dimer (OR 2.80, p = 0.002) and high-intensity thromboprophylaxis regimen (OR 0.20, p = 0.01) were independently associated with thrombotic events. Thirty-one patients (16.5%) experienced haemorrhagic events; among them, 13 were classified as major bleeding according to the International Society on Thrombosis and Haemostasis criteria. Therapeutic anticoagulation, but not the high-intensity thromboprophylaxis regimen, was associated with major bleeding. A proactive approach to the management of thromboembolism in critically ill COVID-19 patients utilising a high-intensity thromboprophylaxis regimen in appropriately selected patients may result in lower thrombotic events without increasing the risk of bleeding.
| S-EPMC7675553 | biostudies-literature
Project description:Background: Outcomes in patients with severe SARS-CoV-2 infection (COVID-19) are conditioned by viral control and regulation of inflammation. Variants in IFIH1, a gene coding the cytoplasmatic RNA sensor MDA5, regulate the response to viral infections. Methods: Patients admitted to an intensive care unit (ICU) with documented COVID-19 were prospectively included and IFIH1 rs1990760 genotypes determined. Peripheral blood gene expression, cell populations and immune mediators were measured during the first day after ICU admission before steroid therapy. Peripheral blood mononuclear cells from healthy volunteers were exposed ex-vivo to an MDA5 agonist and dexamethasone, and changes in gene expression assessed. ICU discharge and hospital death were modelled using rs1990760 variants and dexamethasone therapy as factors. Findings: 237 patients were studied. Patients with the IFIH1 rs1990760 TT variant showed a decrease in expression of inflammation-related pathways, an anti-inflammatory cell profile and a decrease in pro-inflammatory mediators. Cells with TT variant exposed to an MDA5 agonist ex-vivo showed an increase in FOXO3 and IL6 when dexamethasone was added. All patients with the TT variant not treated with steroids (n=14) survived their ICU stay (HR 2.49 95% confidence interval 1.29 – 4.79). Dexamethasone therapy in this subgroup (N=50) delayed ICU discharge and increased hospital mortality (HR 2.19, 95% confidence interval 1.01 – 4.87) and serum IL-6 concentrations. Interpretation: COVID-19 ICU patients with the IFIH1 rs1990760 TT variant show an ameliorated inflammatory response that results in better outcomes than CC/CT variants. Dexamethasone can reverse this anti-inflammatory phenotype, worsening the outcome. Funding: Instituto de Salud Carlos III.
2021-07-03 | GSE168400 | GEO
Project description:In this study, we aim to evaluate the relation between COVID-19 and bacterial secondary superinfections. We assessed the functional responses of neutrophils and monocytes isolated from acute and recovery COVID-19 patients upon bacterial infection using Flow-cytometry and proteomics based assays. Both neutrophils and monocytes showed impared intracellular microbicidal capacity along with a decreased functional response. Determination of plasma cytokines levels showed a significant association of certain cytokines towards secondary bacterial infection.
2021-12-10 | PXD029547 | Pride