Dataset Information

Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19.

ABSTRACT:

Background

Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19).

Objective

To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival.

Design

In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used.

Setting

67 hospitals in the United States.

Participants

Adults with COVID-19 admitted to a participating ICU.

Measurements

Time to death, censored at hospital discharge, or date of last follow-up.

Results

Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]).

Limitation

Observational design.

Conclusion

Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation.

Primary funding source

None.

SUBMITTER: Al-Samkari H

PROVIDER: S-EPMC7863679 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19.

Al-Samkari Hanny H Gupta Shruti S Leaf Rebecca Karp RK Wang Wei W Rosovsky Rachel P RP Brenner Samantha K SK Hayek Salim S SS Berlin Hanna H Kapoor Rajat R Shaefi Shahzad S Melamed Michal L ML Sutherland Anne A Radbel Jared J Green Adam A Garibaldi Brian T BT Srivastava Anand A Leonberg-Yoo Amanda A Shehata Alexandre M AM Flythe Jennifer E JE Rashidi Arash A Goyal Nitender N Chan Lili L Mathews Kusum S KS Hedayati S Susan SS Dy Rajany R Toth-Manikowski Stephanie M SM Zhang Jingjing J Mallappallil Mary M Redfern Roberta E RE Bansal Amar D AD Short Samuel A P SAP Vangel Mark G MG Admon Andrew J AJ Semler Matthew W MW Bauer Kenneth A KA Hernán Miguel A MA Leaf David E DE

Annals of internal medicine 20210126 5

<h4>Background</h4>Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19).<h4>Objective</h4>To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival.<h4>Design</h4>In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after inte ...[more]

PMID: 33493012

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Project description:IntroductionAlthough patients with severe COVID-19 are known to be at high risk of developing thrombotic events, the effects of anticoagulation (AC) dose and duration on in-hospital mortality in critically ill patients remain poorly understood and controversial. The goal of this study was to investigate survival of critically ill COVID-19 patients who received prophylactic or therapeutic dose AC and analyze the mortality rate with respect to detailed demographic and clinical characteristics.Materials and methodsWe conducted a retrospective, observational study of critically ill COVID-19 patients admitted to the ICU at Stony Brook University Hospital in New York who received either prophylactic (n = 158) or therapeutic dose AC (n = 153). Primary outcome was in-hospital death assessed by survival analysis and covariate-adjusted Cox proportional hazard model.ResultsFor the first 3 weeks of ICU stay, we observed similar survival curves for prophylactic and therapeutic AC groups. However, after 3 or more weeks of ICU stay, the therapeutic AC group, characterized by high incidence of acute kidney injury (AKI), had markedly higher death incidence rates with 8.6 deaths (95% CI = 6.2-11.9 deaths) per 1,000 person-days and about 5 times higher risk of death (adj. HR = 4.89, 95% CI = 1.71-14.0, p = 0.003) than the prophylactic group (2.4 deaths [95% CI = 0.9-6.3 deaths] per 1,000 person-days). Among therapeutic AC users with prolonged ICU admission, non-survivors were characterized by older males with depressed lymphocyte counts and cardiovascular disease.ConclusionsOur findings raise the possibility that prolonged use of high dose AC, independent of thrombotic events or clinical background, might be associated with higher risk of in-hospital mortality. Moreover, AKI, age, lymphocyte count, and cardiovascular disease may represent important risk factors that could help identify at-risk patients who require long-term hospitalization with therapeutic dose AC treatment.

Project description:BackgroundThrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.MethodsIn an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.ResultsThe trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis.ConclusionsIn critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).

Project description:BackgroundAcute gastrointestinal bleeding (GIB) may be a severe condition in immunocompromised patients and may require intensive care unit (ICU) admission. We aimed to describe the clinical spectrum of critically ill immunocompromised patients with GIB and identify risk factors associated with mortality and severe GIB defined by hemorrhagic shock, hyperlactatemia and/or the transfusion of more than 5 red blood cells units. Finally, we compared this cohort with a control population of non-immunocompromised admitted in ICU for GIB.ResultsRetrospective study in 3 centers including immunocompromised patients with GIB admitted in ICU from January, 1st 2010 to December, 31rd 2019. Risk factors for mortality and severe GIB were assessed by logistic regression. Immunocompromised patients were matched with a control group of patients admitted in ICU with GIB. A total of 292 patients were analyzed in the study, including 141 immunocompromised patients (compared to a control group of 151 patients). Among immunocompromised patients, upper GIB was more frequent (73%) than lower GIB (27%). By multivariate analysis, severe GIB was associated with male gender (OR 4.48, CI95% 1.75-11.42, p = 0.00), upper GIB (OR 2.88, CI95% 1.11-7.46, p = 0.03) and digestive malignant infiltration (OR 5.85, CI95% 1.45-23.56, p = 0.01). Conversely, proton pump inhibitor treatment before hospitalization was significantly associated with decreased risk of severe GIB (OR 0.25, IC95% 0.10-0.65, p < 0.01). Fifty-four patients (38%) died within 90 days. By multivariate analysis, mortality was associated with hemorrhagic shock (OR 2.91, IC95% 1.33-6.38, p = 0 .01), upper GIB (OR 4.33, CI95% 1.50-12.47, p = 0.01), and long-term corticosteroid therapy before admission (OR 2.98, CI95% 1.32-6.71, p = 0.01). Albuminemia (per 5 g/l increase) was associated with lower mortality (OR 0.54, IC95% 0.35-0.84, p = 0.01). After matching with a control group of non-immunocompromised patients, severity of bleeding was increased in immunocompromised patients, but mortality was not different between the 2 groups.ConclusionMortality is high in immunocompromised patients with GIB in ICU, especially in patients receiving long term corticosteroids. Mortality of GIB is not different from mortality of non-immunocompromised patients in ICU. The prophylactic administration of proton pump inhibitors should be considered in this population.

Project description:Objective: Bleeding can be a severe complication of critical illness, but its true epidemiologic impact on children has seldom been studied. Our objective is to describe the epidemiology of bleeding in critically ill children, using a validated clinical tool, as well as the hemostatic interventions and clinical outcomes associated with bleeding. Design: Prospective observational cohort study. Setting: Tertiary pediatric critical care unit Patients: All consecutive patients (1 month to 18 years of age) admitted to a tertiary pediatric critical care unit Measurements and Main Results: Bleeding events were categorized as minimal, moderate, severe, or fatal, according to the Bleeding Assessment Scale in Critically Ill Children. We collected demographics and severity at admission, as evaluated by the Pediatric Index of Mortality. We used regression models to compare the severity of bleeding with outcomes adjusting for age, surgery, and severity. Over 12 months, 902 critically ill patients were enrolled. The median age was 64 months (IQR 17; 159), the median admission predicted risk of mortality was 0.5% (IQR 0.2; 1.4), and 24% were post-surgical. Eighteen percent of patients experienced at least one bleeding event. The highest severity of bleeding was minimal for 7.9% of patients, moderate for 5.8%, severe for 3.8%, and fatal for 0.1%. Adjusting for age, severity at admission, medical diagnosis, type of surgery, and duration of surgery, bleeding severity was independently associated with fewer ventilator-free days (p < 0.001) and fewer PICU-free days (p < 0.001). Adjusting for the same variables, bleeding severity was independently associated with an increased risk of mortality (adjusted odds ratio for each bleeding category 2.4, 95% CI 1.5; 3.7, p < 0.001). Conclusion: Our data indicate bleeding occurs in nearly one-fifth of all critically ill children, and that higher severity of bleeding was independently associated with worse clinical outcome. Further multicenter studies are required to better understand the impact of bleeding in critically ill children.

Project description:BackgroundDeep vein thrombosis (DVT) is common in critically ill patients with Coronavirus disease 2019 (COVID-19) and may cause fatal pulmonary embolism (PE) prior to diagnosis due to subtle clinical symptoms. The aim of this study was to explore the feasibility of bedside screening for DVT in critically ill COVID-19 patients performed by physicians with limited experience of venous ultrasound. We further aimed to compare inflammation, coagulation and organ dysfunction in patients with and without venous thromboembolism (VTE).MethodsThis observational study included patients with COVID-19 admitted to the intensive care unit (ICU) of a tertiary hospital in Sweden and screened for DVT with proximal compression ultrasound of the lower extremities between April and July 2020. Screening was performed by ICU residents having received a short online education and one hands-on-session. Pathological screening ultrasound was confirmed by formal ultrasound whereas patients with negative screening underwent formal ultrasound on clinical suspicion. Clinical data, laboratory findings and follow-up were extracted from medical records.ResultsOf 90 eligible patients, 56 were screened by seven ICU residents with no (n = 5) or limited (n = 2) previous experience of DVT ultrasound who performed a median of 4 (IQR 2-19) examinations. Four (7.1%) patients had pathological screening ultrasound of which three (5.6%) were confirmed by formal ultrasound. None of the 52 patients with negative screening ultrasound were diagnosed with DVT during follow-up. Six patients were diagnosed with PE of which four prior to negative screening and two following negative and positive screening respectively. Patients with VTE (n = 8) had higher median peak D-dimer (24.0 (IQR 14.2-50.5) vs. 2.8 (IQR 1.7-7.2) mg/L, p = 0.004), mean peak C-reactive protein (363 (SD 80) vs. 285 (SD 108) mg/L, p = 0.033) and median peak plasma creatinine (288 (IQR 131-328) vs. 94 (IQR 78-131) μmol/L, p = 0.009) compared to patients without VTE (n = 48). Five patients (63%) with VTE received continuous renal replacement therapy compared to six patients (13%) without VTE (p = 0.005).ConclusionICU residents with no or limited experience could detect DVT with ultrasound in critically ill COVID-19 patients following a short education. VTE was associated with kidney dysfunction and features of hyperinflammation and hypercoagulation.Trial registrationClinicalTrials ID: NCT04316884 . Registered 20 March 2020.

Dataset Information

Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19.

Background

Objective

Design

Setting

Participants

Measurements

Results

Limitation

Conclusion

Primary funding source

Publications

Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19.

Similar Datasets

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