COVID-19 associated coagulopathy: Thrombosis, hemorrhage and mortality rates with an escalated-dose thromboprophylaxis strategy

Daughety, Molly M.; Morgan, Andrew; Frost, Erin; Kao, Chester; Hwang, Joyce; Tobin, R. F.; Patel, Bhavik; Fuller, Matthew; Welsby, Ian J.; Ortel, Thomas L.

doi:10.1016/j.thromres.2020.10.004

Cited by 35 publications

(46 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thromboembolic events in the context of covid-19 are strongly associated with mortality. 30 36 39 40 41 The cause of elevated thrombosis risk remains unclear, although proposed mechanisms have included systemic inflammation, endothelialitis, and activation of the complement system. 42 43 44 Increases in a variety of inflammatory pathways, including bradykinin, interleukin 6, C reactive protein, and growth differentiation factor 15, have been described in covid-19.…”

Section: Discussionmentioning

confidence: 99%

Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study

Rentsch

Beckman

Tomlinson

et al. 2021

BMJ

190

188

View full text Add to dashboard Cite

Objective To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States. Design Observational cohort study. Setting Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system. Participants All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation. Main outcome measures The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion. Results Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses. Conclusions Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.

show abstract

Section: Discussionmentioning

confidence: 99%

Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study

Rentsch

Beckman

Tomlinson

et al. 2021

BMJ

190

188

View full text Add to dashboard Cite

show abstract

“…The main reasons for the development of thrombotic complications in COVID-19 are uncontrolled inflammatory reaction and coagulopathy in the context of significant endothelial dysfunction ( 16 ). These physio-pathological processes are present in all the stages of the disease with special relevance in patients requiring intensive care unit (ICU) ( 8 , 9 ). However, up to the present time, there are no studies clearly identifying patients at high risk in early stages of SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

“…In line with this, while the incidence of thrombotic complications in critically ill patients is very high, in patients under non-invasive respiratory support (NIS) is still unknown ( 6 , 7 ). The specific incidence of thrombotic events in each of the clinical scenarios within the broad spectrum of severity of COVID-19, is not clearly established, and this has not allowed the implementation of thromboprophylaxis or anticoagulation for routine care in COVID-19 ( 8 , 9 ). In this context, the purpose of the present study was to investigate the cumulative incidence of PE in COVID-19 patients receiving NIS for respiratory failure during their hospitalization.…”

Section: Introductionmentioning

confidence: 99%

Incidence of pulmonary embolism in patients with non-invasive respiratory support during COVID-19 outbreak

González-García

Pascual-Guardia

Colindres

et al. 2021

Respiratory Medicine

View full text Add to dashboard Cite

While the incidence of thrombotic complications in critically ill patients is very high, in patients under non-invasive respiratory support (NIS) is still unknown. The specific incidence of thrombotic events in each of the clinical scenarios within the broad spectrum of severity of COVID-19, is not clearly established, and this has not allowed the implementation of thromboprophylaxis or anticoagulation for routine care in COVID-19. Patients admitted in a semi-critical unit treated initially with NIS, especially Continuous-Positive Airway Pressure (CPAP), were included in the study. The cumulative incidence of pulmonary embolism was analyzed and compared between patients with good response to NIS and patients with clinical deterioration that required orotracheal intubation. 93 patients were included and 16% required mechanical ventilation (MV) after the NIS. The crude cumulative incidence of the PE was 14% (95%, CI 8–22) for all group. In patients that required orotracheal intubation and MV, the cumulative incidence was significantly higher [33% (95%, CI 16-58)] compared to patients that continued with non-invasive support [11% (CI 5-18)] (Log-Rank, p =0.013). Patients that required mechanical ventilation were at higher risk of PE for a HR of 4.3 (95%CI 1.2–16). In conclusion, cumulative incidence of PE is remarkably higher in critically patients with a potential impact in COVID-19 evolution. In this context, patients under NIS are a very high-risk group for developing PE without a clear strategy regarding thromboprophylaxis.

show abstract

“…Thromboembolic events in the context of COVID-19 are strongly associated with mortality. 3,25,31,33,34 The etiology of heightened thrombosis remains unclear, although proposed mechanisms have included systemic inflammation, endothelialitis, and activation of the complement system. [35][36][37] Increases in a variety of inflammatory pathways, including bradykinin, interleukin-6, C-reactive protein, and growth differentiation factor 15, have been described in COVID-19.…”

Section: Comparison With Other Evidencementioning

confidence: 99%

Early initiation of prophylactic anticoagulation for prevention of COVID-19 mortality: a nationwide cohort study of hospitalized patients in the United States

Rentsch

Beckman

Tomlinson

et al. 2020

Preprint

View full text Add to dashboard Cite

ImportanceDeaths among patients with coronavirus disease 2019 (COVID-19) are partially attributed to venous thromboembolism and arterial thromboses. Anticoagulants prevent thrombosis formation, possess anti-inflammatory and anti-viral properties, and may be particularly effective for treating patients with COVID-19.ObjectiveTo evaluate whether initiation of prophylactic anticoagulation within 24 hours of admission is associated with decreased risk of death among patients hospitalized with COVID-19.DesignObservational cohort study.SettingNationwide cohort of patients receiving care in the Department of Veterans Affairs, the largest integrated healthcare system in the United States.ParticipantsAll patients hospitalized with laboratory-confirmed SARS-CoV-2 infection March 1 to July 31, 2020, without a history of therapeutic anticoagulation.ExposuresProphylactic doses of subcutaneous heparin, low-molecular-weight heparin, or direct oral anticoagulants.Main Outcomes and Measures30-day mortality. Secondary outcomes: inpatient mortality and initiating therapeutic anticoagulation.ResultsOf 4,297 patients hospitalized with COVID-19, 3,627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3,600) received subcutaneous heparin or enoxaparin. We observed 622 deaths within 30 days of admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospitalization. In inverse probability of treatment weighted analyses, cumulative adjusted incidence of mortality at 30 days was 14.3% (95% CI 13.1-15.5) among those receiving prophylactic anticoagulation and 18.7% (95% CI 15.1-22.9) among those who did not. Compared to patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30-day mortality (HR 0.73, 95% CI 0.66-0.81). Similar associations were found for inpatient mortality and initiating therapeutic anticoagulation. Quantitative bias analysis demonstrated that results were robust to unmeasured confounding (e-value lower 95% CI 1.77). Results persisted in a number of sensitivity analyses.Conclusions and RelevanceEarly initiation of prophylactic anticoagulation among patients hospitalized with COVID-19 was associated with a decreased risk of mortality. These findings provide strong real-world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial therapy for COVID-19 patients upon hospital admission.

show abstract

COVID-19 associated coagulopathy: Thrombosis, hemorrhage and mortality rates with an escalated-dose thromboprophylaxis strategy

Abstract: Highlights COVID-19 patients are at increased risk of thromboembolic complications. Escalated-dose thromboprophylaxis may help reduce the rate of thromboembolic events. The bleeding risk is highest for patients treated with therapeutic anticoagulation.

Cited by 35 publications

References 10 publications

Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study

Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study

Incidence of pulmonary embolism in patients with non-invasive respiratory support during COVID-19 outbreak

Early initiation of prophylactic anticoagulation for prevention of COVID-19 mortality: a nationwide cohort study of hospitalized patients in the United States

Contact Info

Product

Resources

About