An Original Risk Score to Predict Early Major Bleeding in Acute Pulmonary Embolism

The Syncope, Anemia, Renal Dysfunction (PE-SARD) Bleeding Score


      Improved prediction of the risk of early major bleeding in pulmonary embolism (PE) is needed to optimize acute management.

      Research Question

      Does a simple scoring system predict early major bleeding in acute PE patients, identifying patients with either high or low probability of early major bleeding?

      Study Design and Methods

      From a multicenter prospective registry including 2,754 patients, we performed post hoc multivariable logistic regression analysis to build a risk score to predict early (up to hospital discharge) major bleeding events. We validated the endpoint model internally, using bootstrapping in the derivation dataset by sampling with replacement for 500 iterations. Performances of this novel score were compared with that of the VTE-BLEED (Venous Thrombo-Embolism Bleed), RIETE (Registro informatizado de la enfermedad tromboembólica en España; Computerized Registry of Patients with Venous Thromboembolism), and BACS (Bleeding, Age, Cancer, and Syncope) models.


      Multivariable regression identified three predictors for the occurrence of 82 major bleeds (3.0%; 95% CI, 2.39%-3.72%): Syncope (+1.5); Anemia, defined as hemoglobin <12 g/dL (+2.5); and Renal Dysfunction, defined as glomerular filtration rate <60 mL/min (+1 point) (SARD). The PE-SARD bleeding score was calculated by summing all the components. Overall, 52.2% (95% CI, 50.29%-54.11%) of patients were classified as low bleeding-risk (score, 0 point), 35.2% (95% CI, 33.39%-37.04%) intermediate-risk (score, 1-2.5 points), and 12.6% (95% CI, 9.30%-16.56%) high-risk (score >2.5 points). Observed bleeding rates increased with increasing risk group, from 0.97% (95% CI, 0.53%-1.62%) in the low-risk to 8.93% (95% CI, 6.15%-12.44%) in the high-risk group. C-index was 0.74 (95% CI, 0.73-0.76) and Brier score 0.028 in the derivation cohort. Similar values were calculated from internal bootstrapping. Performance of the PE-SARD score was better than that observed with the VTE-BLEED, RIETE, and BACS scores, leading to a high proportion of bleeding-risk reclassification in patients who bled and those who did not.


      The PE-SARD bleeding risk score is an original, user-friendly score to estimate risk of early major bleeding in patients with acute PE.

      Key Words


      BACS (Bleeding, Age, Cancer, and Syncope), eGFRCKD-EPI (Chronic Kidney Disease Epidemiology Collaboration formula), ESC (European Society of Cardiology), ICH (intracranial hemorrhage), PE (pulmonary embolism), RIETE (Registro informatizado de la enfermedad tromboembólica en España;Computerized Registry of Patients with Venous Thromboembolism), SARD (syncope, anemia, and renal dysfunction), VTE-BLEED (Venous Thrombo-Embolism Bleed)
      To read this article in full you will need to make a payment


      Subscribe to CHEST
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Becattini C.
        • Agnelli G.
        Acute treatment of venous thromboembolism.
        Blood. 2020; 135: 305-316
        • Becattini C.
        • Casazza F.
        • Forgione C.
        • et al.
        Acute pulmonary embolism: external validation of an integrated risk stratification model.
        Chest. 2013; 144: 1539-1545
        • Konstantinides S.V.
        • Meyer G.
        • Becattini C.
        • et al.
        2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).
        Eur Heart J. 2020; 41: 543-603
        • Meyer G.
        • Vicaut E.
        • Danays T.
        • et al.
        Fibrinolysis for patients with intermediate-risk pulmonary embolism.
        N Engl J Med. 2014; 370: 1402-1411
        • Lecumberri R.
        • Alfonso A.
        • Jimenez D.
        • et al.
        Dynamics of case-fatalilty rates of recurrent thromboembolism and major bleeding in patients treated for venous thromboembolism.
        Thromb Haemost. 2013; 110: 834-843
        • Kresoja K.P.
        • Ebner M.
        • Rogge N.I.J.
        • et al.
        Prediction and prognostic importance of in-hospital major bleeding in a real-world cohort of patients with pulmonary embolism.
        Int J Cardiol. 2019; 290: 144-149
        • Prandoni P.
        • Trujillo-Santos J.
        • Sanchez-Cantalejo E.
        • et al.
        Major bleeding as a predictor of mortality in patients with venous thromboembolism: findings from the RIETE Registry.
        J Thromb Haemost. 2010; 8: 2575-2577
        • Klok F.A.
        • Kooiman J.
        • Huisman M.V.
        • et al.
        Predicting anticoagulant-related bleeding in patients with venous thromboembolism: a clinically oriented review.
        Eur Respir J. 2015; 45: 201-210
        • Kearon C.
        • Akl E.A.
        • Ornelas J.
        • et al.
        Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report.
        Chest. 2016; 149: 315-352
        • Klok F.A.
        • Barco S.
        • Konstantinides S.V.
        External validation of the VTE-BLEED score for predicting major bleeding in stable anticoagulated patients with venous thromboembolism.
        Thromb Haemost. 2017; 117: 1164-1170
        • Klok F.A.
        • Hosel V.
        • Clemens A.
        • et al.
        Prediction of bleeding events in patients with venous thromboembolism on stable anticoagulation treatment.
        Eur Respir J. 2016; 48: 1369-1376
        • Ruiz-Gimenez N.
        • Suarez C.
        • Gonzalez R.
        • et al.
        Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism: findings from the RIETE Registry.
        Thromb Haemost. 2008; 100: 26-31
        • Klok F.A.
        • Niemann C.
        • Dellas C.
        • et al.
        Performance of five different bleeding-prediction scores in patients with acute pulmonary embolism.
        J Thromb Thrombolysis. 2016; 41: 312-320
        • Jara-Palomares L.
        • Jimenez D.
        • Bikdeli B.
        • et al.
        Derivation and validation of a clinical prediction rule for thrombolysis-associated major bleeding in patients with acute pulmonary embolism: the BACS score [Published online ahead of print July 23, 2020].
        Eur Respir J. 2020;
        • Meneveau N.
        • Ider O.
        • Seronde M.F.
        • et al.
        Long-term prognostic value of residual pulmonary vascular obstruction at discharge in patients with intermediate- to high-risk pulmonary embolism.
        Eur Heart J. 2013; 34: 693-701
        • Remy-Jardin M.
        • Remy J.
        • Wattinne L.
        • et al.
        Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hold technique: comparison with pulmonary angiography.
        Radiology. 1992; 185: 381-387
        • Investigators P.
        Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED).
        JAMA. 1990; 263: 2753-2759
        • Jaff M.R.
        • McMurtry M.S.
        • Archer S.L.
        • et al.
        Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association.
        Circulation. 2011; 123: 1788-1830
        • Konstantinides S.V.
        2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism.
        Eur Heart J. 2014; 35: 3145-3146
        • Schulman S.
        • Kearon C.
        Subcommittee on Control of Anticoagulation of the S, et al. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients.
        J Thromb Haemost. 2005; 3: 692-694
        • King J.E.
        Running a best-subsets logistic regression: an alternative to stepwise methods.
        Educational and Psychological Measurement. 2003; 63: 392-403
        • KDIGO
        KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.
        Kidney Int Suppl. 2013; 3: 1-150
        • Barnard J.
        • Meng X.L.
        Applications of multiple imputation in medical studies: from AIDS to NHANES.
        Stat Methods Med Res. 1999; 8: 17-36
        • King G.
        • Zeng L.
        Logistic regression in rare events data.
        Political Analysis. 2001; 9: 137-163
        • Johnston R.
        • Jones K.
        • Manley D.
        Confounding and collinearity in regression analysis: a cautionary tale and an alternative procedure, illustrated by studies of British voting behaviour.
        Qual Quant. 2018; 52: 1957-1976
        • Austin P.C.
        Using the bootstrap to improve estimation and confidence intervals for regression coefficients selected using backwards variable elimination.
        Stat Med. 2008; 27: 3286-3300
        • Fine M.J.
        • Auble T.E.
        • Yealy D.M.
        • et al.
        A prediction rule to identify low-risk patients with community-acquired pneumonia.
        N Engl J Med. 1997; 336: 243-250
        • Steyerberg E.W.
        • Eijkemans M.J.
        • Harrell Jr., F.E.
        • et al.
        Prognostic modeling with logistic regression analysis: in search of a sensible strategy in small data sets.
        Med Decis Making. 2001; 21: 45-56
        • Kang L.
        • Chen W.
        • Petrick N.A.
        • et al.
        Comparing two correlated C indices with right-censored survival outcome: a one-shot nonparametric approach.
        Stat Med. 2015; 34: 685-703
        • Cook N.R.
        • Ridker P.M.
        Advances in measuring the effect of individual predictors of cardiovascular risk: the role of reclassification measures.
        Ann Intern Med. 2009; 150: 795-802
        • Natanzon S.S.
        • Matetzky S.
        • Chernomordik F.
        • et al.
        Significance of syncope at presentation among patients with pulmonary emboli.
        Am J Cardiol. 2020; 125: 982-987
        • Kostrubiec M.
        • Plywaczewska M.
        • Jimenez D.
        • et al.
        The prognostic value of renal function in acute pulmonary embolism-a multi-centre cohort study.
        Thromb Haemost. 2019; 119: 140-148
        • Ay C.
        • Pabinger I.
        • Cohen A.T.
        Cancer-associated venous thromboembolism: burden, mechanisms, and management.
        Thromb Haemost. 2017; 117: 219-230
        • Robertson L.
        • Jones L.E.
        Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for the initial treatment of venous thromboembolism.
        Cochrane Database Syst Rev. 2017; 2: CD001100
        • van Es N.
        • Coppens M.
        • Schulman S.
        • et al.
        Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials.
        Blood. 2014; 124: 1968-1975
        • Marti C.
        • John G.
        • Konstantinides S.
        • et al.
        Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis.
        Eur Heart J. 2015; 36: 605-614
        • Kalra R.
        • Bajaj N.S.
        • Arora P.
        • et al.
        Surgical embolectomy for acute pulmonary embolism: systematic review and comprehensive meta-analyses.
        Ann Thorac Surg. 2017; 103: 982-990
        • Kaymaz C.
        • Akbal O.Y.
        • Tanboga I.H.
        • et al.
        Ultrasound-assisted catheter-directed thrombolysis in high-risk and intermediate-high-risk pulmonary embolism: a meta-analysis.
        Curr Vasc Pharmacol. 2018; 16: 179-189
        • Sharifi M.
        • Bay C.
        • Skrocki L.
        • et al.
        Moderate pulmonary embolism treated with thrombolysis (from the “MOPETT” Trial).
        Am J Cardiol. 2013; 111: 273-277
        • Bikdeli B.
        • Chatterjee S.
        • Desai N.R.
        • et al.
        Inferior vena cava filters to prevent pulmonary embolism: systematic review and meta-analysis.
        J Am Coll Cardiol. 2017; 70: 1587-1597
        • Klok F.A.
        • Huisman M.V.
        How I assess and manage the risk of bleeding in patients treated for venous thromboembolism.
        Blood. 2020; 135: 724-734
        • Sanchez O.
        • Trinquart L.
        • Caille V.
        • et al.
        Prognostic factors for pulmonary embolism: the prep study, a prospective multicenter cohort study.
        Am J Respir Crit Care Med. 2010; 181: 168-173
        • Fang M.C.
        • Go A.S.
        • Chang Y.
        • et al.
        A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) study.
        J Am Coll Cardiol. 2011; 58: 395-401