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

Al‐Samkari, Hanny; Gupta, Shruti; Leaf, Rebecca Karp; Wang, Wei; Rosovsky, Rachel; Brenner, Samantha K.; Hayek, Salim S.; Berlin, Hanna; Kapoor, Rajat; Shaefi, Shahzad; Melamed, Michal L.; Sutherland, Anne; Radbel, Jared; Green, Adam; Garibaldi, Brian T.; Srivastava, Anand; Leonberg‐Yoo, Amanda K.; Shehata, Alexandre M.; Flythe, Jennifer E.; Rashidi, Arash; Goyal, Nitender; Chan, Lili; Mathews, Kusum S.; Hedayati, S. Susan; Dy, Rajany; Toth‐Manikowski, Stephanie M.; Zhang, Jingjing; Mallappallil, Mary; Redfern, Roberta E.; Bansal, Amar D.; Short, Samuel A.P.; Vangel, Mark; Admon, Andrew J.; Semler, Matthew W.; Bauer, Kenneth A.; Hernán, Miguel A.; Leaf, David E.

doi:10.7326/m20-6739

Cited by 103 publications

(154 citation statements)

References 37 publications

(22 reference statements)

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“…32 Another study in critically ill patients with COVID-19 found that two-thirds of major bleeding events occurred while patients were receiving therapeutic-intensity anticoagulation. 33 Together with our 34 To minimize misclassification of bleeding events, we required documentation of bleeding in the progress notes or imaging reports and were rigorous in our adjudication of events.…”

Section: Discussionmentioning

confidence: 99%

“…With the classification not remaining constant over time, it was challenging to study the effect of the intensity of anticoagulation on bleeding. The majority of previous studies on COVID-19 have not accounted for changes in anticoagulant intensity during hospital admission 14,15,33. We attempted to account for these changes by assessing anticoagulation intensity as a time-varying covariate.…”

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confidence: 99%

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Bleeding risk by intensity of anticoagulation in critically ill patients with COVID‐19: A retrospective cohort study

Halaby

Cuker

Yui

et al. 2021

Journal of Thrombosis and Haemostasis

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Background: Studies report hypercoagulability in coronavirus disease 2019 , leading many institutions to escalate anticoagulation intensity for thrombosis prophylaxis.Objective: To determine the bleeding risk with various intensities of anticoagulation in critically ill patients with COVID-19 compared with other respiratory viral illnesses (ORVI).Patients/Methods: This retrospective cohort study compared the incidence of major bleeding in patients admitted to an intensive care unit (ICU) within a single health system with COVID-19 versus ORVI. In the COVID-19 cohort, we assessed the effect of anticoagulation intensity received on ICU admission on bleeding risk. We performed a secondary analysis with anticoagulation intensity as a time-varying covariate to reflect dose changes after ICU admission.Results: Four hundred and forty-three and 387 patients were included in the COVID-19 and ORVI cohorts, respectively. The hazard ratio of major bleeding for the COVID-19 cohort relative to the ORVI cohort was 1.26 (95% confidence interval [CI]: 0.86-1.86). In COVID-19 patients, an inverse-probability treatment weighted model found therapeutic-intensity anticoagulation on ICU admission had an adjusted hazard ratio of bleeding of 1.55 (95% CI: 0.88-2.73) compared with standard prophylacticintensity anticoagulation. However, when anticoagulation was assessed as a timevarying covariate and adjusted for other risk factors for bleeding, the adjusted hazard ratio for bleeding on therapeutic-intensity anticoagulation compared with standard thromboprophylaxis was 2.59 (95% CI: 1.20-5.57). Conclusions:Critically ill patients with COVID-19 had a similar bleeding risk as ORVI patients. When accounting for changes in anticoagulation that occurred in COVID-19 patients, therapeutic-intensity anticoagulation was associated with a greater risk of major bleeding compared with standard thromboprophylaxis.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Bleeding risk by intensity of anticoagulation in critically ill patients with COVID‐19: A retrospective cohort study

Halaby

Cuker

Yui

et al. 2021

Journal of Thrombosis and Haemostasis

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“…As additional data on thromboprophylaxis in COVID-19 continues to surface, international guidelines suggest a need for a risk-adapted approach to thromboprophylaxis [ 3 – 5 ]. Notably, while 21.0% of our study population was identified as low VTE risk, nearly half (45.5%) of patients were identified as high VTE risk.…”

Section: Discussionmentioning

confidence: 99%

“…More recent data in medical ward patients show VTE rates up to 6.2% [ 2 ], which is still substantially higher than historical rates of VTE in hospitalized non-COVID medical populations. Indeed, VTE risk in hospitalized COVID-19 patients remains a serious concern [ 2 , 3 ]. Antithrombotic guidelines recommend a universal thromboprophylaxis strategy for COVID-19 inpatients, and suggest intermediate-dose anticoagulation may be beneficial in subsets of high-risk patients [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

External validation of the IMPROVE-DD risk assessment model for venous thromboembolism among inpatients with COVID-19

Goldin

Lin

Kohn

et al. 2021

J Thromb Thrombolysis

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There is a need to discriminate which COVID-19 inpatients are at higher risk for venous thromboembolism (VTE) to inform prophylaxis strategies. The IMPROVE-DD VTE risk assessment model (RAM) has previously demonstrated good discrimination in non-COVID populations. We aimed to externally validate the IMPROVE-DD VTE RAM in medical patients hospitalized with COVID-19. This retrospective cohort study evaluated the IMPROVE-DD VTE RAM in adult patients with COVID-19 admitted to one of thirteen Northwell Health hospitals in the New York metropolitan area between March 1, 2020 and April 27, 2020. VTE was defined as new-onset symptomatic deep venous thrombosis or pulmonary embolism. To assess the predictive value of the RAM, the receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Of 9407 patients who met study criteria, 274 patients developed VTE with a prevalence of 2.91%. The VTE rate was 0.41% for IMPROVE-DD score 0–1 (low risk), 1.21% for score 2–3 (moderate risk), and 5.30% for score ≥ 4 (high risk). Approximately 45.7% of patients were classified as high VTE risk, 33.3% moderate risk, and 21.0% low risk. Discrimination of low versus moderate-high VTE risk demonstrated sensitivity 0.971, specificity 0.215, PPV 0.036, and NPV 0.996. ROC AUC was 0.703. In this external validation study, the IMPROVE-DD VTE RAM demonstrated very good discrimination to identify hospitalized COVID-19 patients at low, moderate, and high VTE risk.

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“…36 In addition, findings from two large-scale multicenter studies report lower rates of thrombotic events than initially anticipated. 12,37 Other studies have suggested that many VTE events in COVID-19 are distal deep vein thrombosis or subsegmental pulmonary embolism, 13,34 which are less likely to impact mortality. Of note, we did not notice a difference in the rate of all-cause mortality in the two study groups.…”

Section: Standard-dosementioning

confidence: 99%

Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial

Bikdeli¹,

Talasaz²,

Rashidi³

et al. 2021

Thromb Haemost

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Background: Thrombotic complications are considered among the main extrapulmonary manifestations of COVID-19. The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. Methods: This manuscript reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. Results: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]; 62 (50, 71) years; 237 (42.2%) women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate-dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, P=0.11). No significant differences were observed between the two groups for other efficacy outcomes, or in the landmark analysis from days 31-90. Overall, there were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24, P=0.33). Conclusion: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

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

Cited by 103 publications

References 37 publications

Bleeding risk by intensity of anticoagulation in critically ill patients with COVID‐19: A retrospective cohort study

Bleeding risk by intensity of anticoagulation in critically ill patients with COVID‐19: A retrospective cohort study

External validation of the IMPROVE-DD risk assessment model for venous thromboembolism among inpatients with COVID-19

Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial

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