Anti-Xa Directed Thromboprophylaxis in Critically Ill Patients with Coronavirus Disease 2019.
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ABSTRACT:
SUBMITTER: Mohamed A
PROVIDER: S-EPMC9358597 | biostudies-literature | 2022 Jan-Dec
REPOSITORIES: biostudies-literature
Publications
Anti-Xa Directed Thromboprophylaxis in Critically Ill Patients with Coronavirus Disease 2019.
Mohamed Adham A Shemanski Shelby M SM Saad Mohamed O MO Ploetz Jeannette J Haines Michelle M MM Schlachter Andrew B AB Hamarshi Majdi S MS
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 20220101
<b>Objective:</b> To compare Anti-Xa directed thromboprophylaxis using low molecular weight heparin (LMWH) (anti-Xa peak goal 0.2-0.5 IU/mL) to alternative anticoagulation strategies in critically ill COVID-19 patients. <b>Methods:</b> This was a retrospective, multicenter, single health-system study. Primary outcomes were thromboembolic events and clinically important bleeding events. Secondary outcomes included dosing comparisons between LMWH cohorts. <b>Main Results:</b> A total of 695 patien ...[more]
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Project description:ObjectivesTo assess the role of thromboprophylaxis regimens on the occurrence of pulmonary embolism in coronavirus disease 2019 patients.DesignRetrospective analysis of prospectively collected data on coronavirus disease 2019 patients, included between March 10, and April 30, 2020.SettingICU of an University Hospital in Belgium.Patients and interventionsCritically ill adult mechanically ventilated coronavirus disease 2019 patients were eligible if they underwent a CT pulmonary angiography, as part of the routine management in case of persistent hypoxemia or respiratory deterioration. The primary endpoint of this study was the occurrence of pulmonary embolism according to the use of standard thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units once daily) or high regimen thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units bid or therapeutic unfractioned heparin).Measurements and main resultsOf 49 mechanically ventilated coronavirus disease 2019, 40 underwent CT pulmonary angiography after a median of 7 days (4-8 d) since ICU admission and 12 days (9-16 d) days since the onset of symptoms. Thirteen patients (33%) were diagnosed of pulmonary embolism, which was bilateral in six patients and localized in the right lung in seven patients. D-dimers on the day of CT pulmonary angiography had a predictive accuracy of 0.90 (95% CIs: 0.78-1.00) for pulmonary embolism. The use of high-regimen thromboprophylaxis was associated with a lower occurrence of pulmonary embolism (2/18; 11%) than standard regimen (11/22, 50%-odds ratio 0.13 [0.02-0.69]; p = 0.02); this difference remained significant even after adjustment for confounders. Six patients with pulmonary embolism (46%) and 14 patients without pulmonary embolism (52%) died at ICU discharge (odds ratio 0.79 [0.24-3.26]; p = 0.99).ConclusionsIn this study, one third of coronavirus disease 2019 mechanically ventilated patients have a pulmonary embolism visible on CT pulmonary angiography. High regimen thromboprophylaxis may decrease the occurrence of such complication.
| S-EPMC7437413 | biostudies-literature
Project description:ObjectivesCoronavirus disease 2019 is caused by severe acute respiratory syndrome-coronavirus-2 infection to which there is no community immunity. Patients admitted to ICUs have high mortality, with only supportive therapies available. Our aim was to profile plasma inflammatory analytes to help understand the host response to coronavirus disease 2019.DesignDaily blood inflammation profiling with immunoassays.SettingTertiary care ICU and academic laboratory.SubjectsAll patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome-coronavirus-2, using standardized hospital screening methodologies, had daily blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative), or until ICU day 7 if the patient was positive (coronavirus disease 2019 positive).InterventionsNone.Measurements and main resultsAge- and sex-matched healthy controls and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients were more likely than coronavirus disease 2019 negative patients to suffer bilateral pneumonia. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. We measured 57 inflammatory analytes and then analyzed with both conventional statistics and machine learning. Twenty inflammatory analytes were different between coronavirus disease 2019 positive patients and healthy controls (p < 0.01). Compared with coronavirus disease 2019 negative patients, coronavirus disease 2019 positive patients had 17 elevated inflammatory analytes on one or more of their ICU days 1-3 (p < 0.01), with feature classification identifying the top six analytes between cohorts as tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2. While tumor necrosis factor, granzyme B, heat shock protein 70, and interleukin-18 were elevated for all seven ICU days, interferon-gamma-inducible protein 10 transiently elevated on ICU days 2 and 3 and elastase 2 increased over ICU days 2-7. Inflammation profiling predicted coronavirus disease 2019 status with 98% accuracy, whereas elevated heat shock protein 70 was strongly associated with mortality.ConclusionsWhile many inflammatory analytes were elevated in coronavirus disease 2019 positive ICU patients, relative to healthy controls, the top six analytes distinguishing coronavirus disease 2019 positive ICU patients from coronavirus disease 2019 negative ICU patients were tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10, and elastase 2.
| S-EPMC7314329 | biostudies-literature
Project description:BackgroundSevere acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causes direct lung damage, overwhelming endothelial activation, and inflammatory reaction, leading to acute respiratory failure and multi-organ dysfunction. Ongoing clinical trials are evaluating targeted therapies to hinder this exaggerated inflammatory response. Critically ill coronavirus disease 2019 (COVID-19) patients have shown heterogeneous severity trajectories, suggesting that response to therapies is likely to vary across patients.Research questionAre critically ill COVID-19 patients biologically and immunologically dissociable based on profiling of currently evaluated therapeutic targets?Study design and methodsWe did a single-center, prospective study in an ICU department in France. Ninety-six critically ill adult patients admitted with a documented SARS-CoV-2 infection were enrolled. We conducted principal components analysis and hierarchical clustering on a vast array of immunologic variables measured on the day of ICU admission.ResultsWe found that patients were distributed in three clusters bearing distinct immunologic features and associated with different ICU outcomes. Cluster 1 had a "humoral immunodeficiency" phenotype with predominant B-lymphocyte defect, relative hypogammaglobulinemia, and moderate inflammation. Cluster 2 had a "hyperinflammatory" phenotype, with high cytokine levels (IL-6, IL-1β, IL-8, tumor necrosis factor-alpha [TNF⍺]) associated with CD4+ and CD8+ T-lymphocyte defects. Cluster 3 had a "complement-dependent" phenotype with terminal complement activation markers (elevated C3 and sC5b-9).InterpretationPatients with severe COVID-19 exhibiting cytokine release marks, complement activation, or B-lymphocyte defects are distinct from each other. Such immunologic variability argues in favor of targeting different mediators in different groups of patients and could serve as a basis for patient identification and clinical trial eligibility.
| S-EPMC7831685 | biostudies-literature
Project description:BackgroundCardiac injury has been reported in up to 30% of coronavirus disease 2019 (COVID-19) patients. However, cardiac injury is defined mainly by troponin elevation without description of associated structural abnormalities and its time course has not been studied.Research questionWhat are the ECG and echocardiographic abnormalities as well as their time course in critically ill COVID-19 patients?Study design and methodsThe cardiac function of 43 consecutive COVID-19 patients admitted to two ICUs was assessed prospectively and repeatedly, combining ECG, cardiac biomarker, and transthoracic echocardiographic analyses from ICU admission to ICU discharge or death or to a maximum follow-up of 14 days. Cardiac injury was defined by troponin elevation and newly diagnosed ECG or echocardiographic abnormalities, or both.ResultsAt baseline, 49% of patients demonstrated a cardiac injury, and 70% of patients experienced cardiac injury within the first 14 days of ICU stay, with a median time of occurrence of 3 days (range, 0-7 days). The most frequent abnormalities were ECG or echocardiographic signs, or both, of left ventricular (LV) abnormalities (87% of patients with cardiac injury), right ventricular (RV) systolic dysfunction (47%), pericardial effusion (43%), new-onset atrial arrhythmias (33%), LV relaxation impairment (33%), and LV systolic dysfunction (13%). Between baseline and day 14, the incidence of pericardial effusion and of new-onset atrial arrhythmias increased and the incidence of ECG or echocardiographic signs, or both, of LV abnormalities as well as the incidence of LV relaxation impairment remained stable, whereas the incidence of RV and LV systolic dysfunction decreased.InterpretationCardiac injury is common and early in critically ill COVID-19 patients. ECG or echocardiographic signs, or both, of LV abnormalities were the most frequent abnormalities, and patients with cardiac injury experienced more RV than LV systolic dysfunction.
| S-EPMC7591864 | biostudies-literature
Project description:ObjectivesHypercoagulability may be a key mechanism for acute organ injury and death in patients with severe coronavirus disease 2019, but the relationship between elevated plasma levels of d-dimer, a biomarker of coagulation activation, and mortality has not been rigorously studied. We examined the independent association between d-dimer and death in critically ill patients with coronavirus disease 2019.DesignMulticenter cohort study.SettingICUs at 68 hospitals across the United States.PatientsCritically ill adults with coronavirus disease 2019 admitted to ICUs between March 4, 2020, and May 25, 2020, with a measured d-dimer concentration on ICU day 1 or 2.InterventionsNone.Measurements and main resultsThe primary exposure was the highest normalized d-dimer level (assessed in four categories: < 2×, 2-3.9×, 4-7.9×, and ≥ 8× the upper limit of normal) on ICU day 1 or 2. The primary endpoint was 28-day mortality. Multivariable logistic regression was used to adjust for confounders. Among 3,418 patients (63.1% male; median age 62 yr [interquartile range, 52-71 yr]), 3,352 (93.6%) had a d-dimer concentration above the upper limit of normal. A total of 1,180 patients (34.5%) died within 28 days. Patients in the highest compared with lowest d-dimer category had a 3.11-fold higher odds of death (95% CI, 2.56-3.77) in univariate analyses, decreasing to a 1.81-fold increased odds of death (95% CI, 1.43-2.28) after multivariable adjustment for demographics, comorbidities, and illness severity. Further adjustment for therapeutic anticoagulation did not meaningfully attenuate this relationship (odds ratio, 1.73; 95% CI, 1.36-2.19).ConclusionsIn a large multicenter cohort study of critically ill patients with coronavirus disease 2019, higher d-dimer levels were independently associated with a greater risk of death.
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Project description:Background Anti-factor Xa activity has been suggested as a surrogate parameter for judging the effectiveness of pharmacological thromboprophylaxis with low molecular weight heparins in critically ill patients. However, this practice is not supported by evidence associating low anti-factor Xa activity with venous thromboembolism. Methods We performed a retrospective observational study including 1,352 critically ill patients admitted to 6 intensive care units of the Medical University of Vienna, Austria between 01/2015 and 12/2018. Included patients received prophylactically dosed enoxaparin (≤100 IU/kg body weight per day). We analyzed median peak, 12-h trough and 24-h trough anti-factor Xa activity per patient and compared anti-factor Xa activity between patients without vs. with venous thromboembolic events. Results 19 patients (1.4%) developed a total of 22 venous thromboembolic events. We did not observe a difference of median (IQR) anti-factor Xa activity between patients without venous thromboembolism [peak 0.22 IU/mL (0.14–0.32); 12-h trough 0.1 IU/mL (<0.1–0.17), 24-h trough < 0.1 IU/mL (<0.1– <0.1)] vs. patients with venous thromboembolism [peak 0.33 IU/mL (0.14–0.34); 12-h trough 0.12 IU/mL (<0.1–0.26); 24-h trough < 0.1 IU/mL (<0.1–<0.1)]. Conclusion Patients who developed venous thromboembolism had anti-factor Xa activities comparable to those who did not suffer from venous thromboembolism.
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Project description:To describe the epidemiology of superinfections (occurring > 48 hr after hospital admission) and their impact on the ICU and 28-day mortality in patients with coronavirus disease 2019 with acute respiratory distress syndrome, requiring mechanical ventilation.DesignRetrospective analysis of prospectively collected observational data.SettingUniversity-affiliated adult ICU.PatientsNinety-two coronavirus disease 2019 patients admitted to the ICU from February 21, 2020, to May 6, 2020.InterventionsNone.Measurements and main resultsThe prevalence of superinfection at ICU admission was 21.7%, and 53 patients (57.6%) had at least one superinfection during ICU stay, with a total of 75 (82%) ventilator-associated pneumonia and 57 (62%) systemic infections. The most common pathogens responsible for ventilator-associated pneumonia were Pseudomonas aeruginosa (n = 26, 34.7%) and Stenotrophomonas maltophilia (n = 14, 18.7%). Bloodstream infection occurred in 16 cases, including methicillin-resistant Staphylococcus epidermidis (n = 8, 14.0%), Enterococcus species (n = 6, 10.5%), and Streptococcus species (n = 2, 3.5%). Fungal infections occurred in 41 cases, including 36 probable (30 by Candida albicans, six by C. nonalbicans) and five proven invasive candidiasis (three C. albicans, two C. nonalbicans). Presence of bacterial infections (odds ratio, 10.53; 95% CI, 2.31-63.42; p = 0.005), age (odds ratio, 1.17; 95% CI, 1.07-1.31; p = 0.001), and the highest Sequential Organ Failure Assessment score (odds ratio, 1.27; 95% CI, 1.06-1.63; p = 0.032) were independently associated with ICU or 28-day mortality.ConclusionsPrevalence of superinfections in coronavirus disease 2019 patients requiring mechanical ventilation was high in this series, and bacterial superinfections were independently associated with ICU or 28-day mortality (whichever comes first).
| S-EPMC8202543 | biostudies-literature
Project description:ObjectivesCritically ill patients with coronavirus disease 2019 have variable mortality. Risk scores could improve care and be used for prognostic enrichment in trials. We aimed to compare machine learning algorithms and develop a simple tool for predicting 28-day mortality in ICU patients with coronavirus disease 2019.DesignThis was an observational study of adult patients with coronavirus disease 2019. The primary outcome was 28-day inhospital mortality. Machine learning models and a simple tool were derived using variables from the first 48 hours of ICU admission and validated externally in independent sites and temporally with more recent admissions. Models were compared with a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 using the area under the receiver operating characteristic curve and calibration.SettingSixty-eight U.S. ICUs.PatientsAdults with coronavirus disease 2019 admitted to 68 ICUs in the United States between March 4, 2020, and June 29, 2020.InterventionsNone.Measurements and main resultsThe study included 5,075 patients, 1,846 (36.4%) of whom died by day 28. eXtreme Gradient Boosting had the highest area under the receiver operating characteristic curve in external validation (0.81) and was well-calibrated, while k-nearest neighbors were the lowest performing machine learning algorithm (area under the receiver operating characteristic curve 0.69). Findings were similar with temporal validation. The simple tool, which was created using the most important features from the eXtreme Gradient Boosting model, had a significantly higher area under the receiver operating characteristic curve in external validation (0.78) than the Sequential Organ Failure Assessment score (0.69), National Early Warning Score (0.60), and CURB-65 (0.65; p < 0.05 for all comparisons). Age, number of ICU beds, creatinine, lactate, arterial pH, and Pao2/Fio2 ratio were the most important predictors in the eXtreme Gradient Boosting model.ConclusionseXtreme Gradient Boosting had the highest discrimination overall, and our simple tool had higher discrimination than a modified Sequential Organ Failure Assessment score, National Early Warning Score, and CURB-65 on external validation. These models could be used to improve triage decisions and clinical trial enrichment.
| S-EPMC8378790 | biostudies-literature
Project description:ObjectivesCoronavirus disease 2019 is associated with high mortality rates and multiple organ damage. There is increasing evidence that these patients are at risk for various cardiovascular insults; however, there are currently no guidelines for the diagnosis and management of such cardiovascular complications in patients with coronavirus disease 2019. We share data and recommendations from a multidisciplinary team to highlight our institution's clinical experiences and guidelines for managing cardiovascular complications of coronavirus disease 2019.Design setting and patientsThis was a retrospective cohort study of patients admitted to one of six ICUs dedicated to the care of patients with coronavirus disease 2019 located in three hospitals within one academic medical center in Atlanta, Georgia.Measurements/interventionsChart review was conducted for sociodemographic, laboratory, and clinical data. Rates of specific cardiovascular complications were assessed, and data were analyzed using a chi-square or Wilcoxon rank-sum test for categorical and continuous variables. Additionally, certain cases are presented to demonstrate the sub committee's recommendations.Main resultsTwo-hundred eighty-eight patients were admitted to the ICU with coronavirus disease 2019. Of these, 86 died (29.9%), 242 (84.03%) had troponin elevation, 70 (24.31%) had dysrhythmias, four (1.39%) had ST-elevation myocardial infarction, eight (2.78%) developed cor pulmonale, and 190 (65.97%) with shock. There was increased mortality risk in patients with greater degrees of troponin elevation (p < 0.001) and with the development of arrhythmias (p < 0.001), cor pulmonale (p < 0.001), and shock (p < 0.001).ConclusionsWhile there are guidelines for the diagnosis and management of pulmonary complications of coronavirus disease 2019, there needs to be more information regarding the management of cardiovascular complications as well. These recommendations garnered from the coronavirus disease 2019 cardiology subcommittee from our institution will add to the existing knowledge of these potential cardiovascular insults as well as highlight suggestions for the diagnosis and management of the range of cardiovascular complications of coronavirus disease 2019. Additionally, with the spread of coronavirus disease 2019, our case-based recommendations provide a bedside resource for providers newly caring for patients with coronavirus disease 2019.
| S-EPMC7717747 | biostudies-literature
Project description:ObjectivesTo determine delirium occurrence rate, duration, and severity in patients admitted to the ICU with coronavirus disease 2019.DesignRetrospective data extraction study from March 1, 2020, to June 7, 2020. Delirium outcomes were assessed for up to the first 14 days in ICU.SettingTwo large, academic centers serving the state of Indiana.PatientsConsecutive patients admitted to the ICU with positive severe acute respiratory syndrome coronavirus 2 nasopharyngeal swab polymerase chain reaction test from March 1, 2020, to June 7, 2020, were included. Individuals younger than 18 years of age, without any delirium assessments, or without discharge disposition were excluded.Measurements and main resultsPrimary outcomes were delirium rates and duration, and the secondary outcome was delirium severity. Two-hundred sixty-eight consecutive patients were included in the analysis with a mean age of 58.4 years (sd, 15.6 yr), 40.3% were female, 44.4% African American, 20.7% Hispanic, and a median Acute Physiology and Chronic Health Evaluation II score of 18 (interquartile range, 13-25). Delirium without coma occurred in 29.1% of patients, delirium prior to coma in 27.9%, and delirium after coma in 23.1%. The first Confusion Assessment Method for the ICU assessment was positive for delirium in 61.9%. Hypoactive delirium was the most common subtype (87.4%). By day 14, the median number of delirium/coma-free were 5 days (interquartile range, 4-11 d), and median Confusion Assessment Method for the ICU-7 score was 6.5 (interquartile range, 5-7) indicating severe delirium. Benzodiazepines were ordered for 78.4% of patients in the cohort. Mechanical ventilation was associated with greater odds of developing delirium (odds ratio, 5.0; 95% CI, 1.1-22.2; p = 0.033) even after adjusting for sedative medications. There were no between-group differences in mortality.ConclusionsDelirium without coma occurred in 29.1% of patients admitted to the ICU. Delirium persisted for a median of 5 days and was severe. Mechanical ventilation was significantly associated with odds of delirium even after adjustment for sedatives. Clinical attention to manage delirium duration and severity, and deeper understanding of the virus' neurologic effects is needed for patients with coronavirus disease 2019.
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