Anticipating and managing coagulopathy and thrombotic manifestations of severe COVID-19

Godoy, Lucas C.; Goligher, Ewan C.; Lawler, Patrick R.; Slutsky, Arthur S.; Zarychanski, Ryan

doi:10.1503/cmaj.201240

Cited by 46 publications

(43 citation statements)

References 74 publications

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“…SARS-CoV-2 may in part promote pulmonary coagulopathy by a direct effect on bronchial epithelial cells via activation of tissue factor signaling and impairment of epithelial anticoagulant mechanism (34). Notably, stronger activation of coagulation locally versus systemically in our ICU/ARDS cohort does not preclude a role for systemic coagulation activation in various thromboembolic and vascular events in COVID-19 in general (35). tPA/PAI-1 ratio's were not different between groups in BALF and only modestly elevated in plasma of patients, arguing against a strongly disturbed fibrinolyic balance in COVID-19 patients and suggesting that elevated D-dimer levels reflect enhanced coagulation rather than hyperfibrinolysis.…”

Section: Discussionmentioning

confidence: 74%

Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients

et al. 2021

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RationaleSystemic activation of procoagulant and inflammatory mechanisms has been implicated in the pathogenesis of COVID-19. Knowledge of activation of these host response pathways in the lung compartment of COVID-19 patients is limited.ObjectivesTo evaluate local and systemic activation of coagulation and interconnected inflammatory responses in critically ill COVID-19 patients with persistent acute respiratory distress syndrome.MethodsPaired bronchoalveolar lavage fluid and plasma samples were obtained from 17 patients with COVID-19 related persistent acute respiratory distress syndrome (mechanical ventilation > 7 days) 1 and 2 weeks after start mechanical ventilation and compared with 8 healthy controls. Thirty-four host response biomarkers stratified into five functional domains (coagulation, complement system, cytokines, chemokines and growth factors) were measured.Measurements and Main ResultsIn all patients, all functional domains were activated, especially in the bronchoalveolar compartment, with significantly increased levels of D-dimers, thrombin-antithrombin complexes, soluble tissue factor, C1-inhibitor antigen and activity levels, tissue type plasminogen activator, plasminogen activator inhibitor type I, soluble CD40 ligand and soluble P-selectin (coagulation), next to activation of C3bc and C4bc (complement) and multiple interrelated cytokines, chemokines and growth factors. In 10 patients in whom follow-up samples were obtained between 3 and 4 weeks after start mechanical ventilation many bronchoalveolar and plasma host response biomarkers had declined.ConclusionsCritically ill, ventilated patients with COVID-19 show strong responses relating to coagulation, the complement system, cytokines, chemokines and growth factors in the bronchoalveolar compartment. These results suggest a local pulmonary rather than a systemic procoagulant and inflammatory “storm” in severe COVID-19.

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Section: Discussionmentioning

confidence: 74%

Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients

et al. 2021

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“…We describe use of thoracic computed tomography (CT), because of its role in diagnosis of COVID-19, 17 and in-hospital use of antibiotics that are known to be used for respiratory infections (see Appendix 1), [18][19][20] anticoagulants and systemic corticosteroids, as captured by medication orders after admission. Use of these medications may be associated with COVID-19, 21,22 although our study period was before the publication of the RECOVERY trial's results regarding dexamethasone. 21 We used codes from the Canadian Classification of Health Interventions, as reported to CIHI, to identify the use of invasive mechanical ventilation, dialysis (including both newly initiated and chronic dialysis) and gastrointestinal endoscopy and bronchoscopy.…”

Section: Outcomes and Process Measuresmentioning

confidence: 99%

Characteristics and outcomes of hospital admissions for COVID-19 and influenza in the Toronto area

Verma

Hora

Jung

et al. 2021

CMAJ

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I nternational studies report that patients admitted to hospital with coronavirus disease 2019 (COVID-19) have high rates of critical illness and mortality. 1-5 Two small Canadian case series have described care for critically ill patients with COVID-19 and found mortality rates of up to 25%. 6,7 However, outcomes of patients admitted to hospital for COVID-19 in Canada are not well described, particularly outside of intensive care units (ICUs). Case fatality rates for COVID-19 vary dramatically worldwide, 8 and outcomes of patients admitted to hospital for COVID-19 in Canada may differ from other countries because of differences in populations, public health and health care systems. Seasonal influenza is a useful comparator for COVID-19 9-11 as it is another respiratory virus, familiar to the general public, with high rates of morbidity and mortality. The purpose of this study was to describe patient characteristics, resource use, clinical care and outcomes for patients admitted to hospital with COVID-19 in Ontario, Canada, using influenza as a comparator. We also validated the performance of various prognostic risk scores for in-hospital mortality among patients with COVID-19.

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“…[1][2][3][4] Critically ill patients with Covid-19 are at high risk of venous and arterial thrombotic events despite standard dose pharmacological thromboprophylaxis. [5][6][7][8] Higher levels of circulating biomarkers reflecting systemic inflammation and coagulation activation (e.g., D-dimer, C-reactive protein) are independently associated with a greater risk of respiratory failure, thrombosis, and death. 2,9,10 Thrombotic processes may therefore be an important cause of poor outcome from Covid-19.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Anticoagulation in Critically Ill Patients with Covid-19 – Preliminary Report

Zarychanski

2021

Preprint

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Background Thrombosis may contribute to morbidity and mortality in Covid-19. We hypothesized that therapeutic anticoagulation would improve outcomes in critically ill patients with Covid-19. Methods We conducted an open-label, adaptive, multiplatform, randomized, clinical trial. Patients with severe Covid-19, defined as the requirement for organ support with high flow nasal cannula, non-invasive ventilation, invasive ventilation, vasopressors, or inotropes, were randomized to receive therapeutic anticoagulation with heparin or pharmacological thromboprophylaxis as per local usual care. The primary outcome was an ordinal scale combining in-hospital mortality (assigned -1) and days free of organ support to day 21. Results Therapeutic anticoagulation met the pre-defined criteria for futility in patients with severe Covid-19. The primary outcome was available for 1,074 participants (529 randomized to therapeutic anticoagulation and 545 randomized to usual care pharmacological thromboprophylaxis). Median organ support-free days were 3 days (interquartile range -1, 16) in patients assigned to therapeutic anticoagulation and 5 days (interquartile range -1, 16) in patients assigned to usual care pharmacological thromboprophylaxis (adjusted odds ratio 0.87, 95% credible interval (CrI) 0.70-1.08, posterior probability of futility [odds ratio<1.2] 99.8%). Hospital survival was comparable between groups (64.3% vs. 65.3%, adjusted odds ratio 0.88, 95% CrI 0.67-1.16). Major bleeding occurred in 3.1% of patients assigned to therapeutic anticoagulation and 2.4% of patients assigned to usual care pharmacological thromboprophylaxis. Conclusions In patients with severe Covid-19, therapeutic anticoagulation did not improve hospital survival or days free of organ support compared to usual care pharmacological thromboprophylaxis.

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Anticipating and managing coagulopathy and thrombotic manifestations of severe COVID-19

Cited by 46 publications

References 74 publications

Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients

Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients

Characteristics and outcomes of hospital admissions for COVID-19 and influenza in the Toronto area

Therapeutic Anticoagulation in Critically Ill Patients with Covid-19 – Preliminary Report

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