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Prediction of Early Major Bleeding in Acute PE

January 25, 2022

Written by Bo Stubblefield

Spoon Feed
A new risk score (PE-SARD) stratifies patients with acute pulmonary embolism (PE) to predict early, major bleeding events.

Why does this matter?
Prior scores such as VTE-BLEED(1), RIETE(2), and BACS(3) have been derived to predict major bleeding(4) in various patient populations with venous thromboembolism (VTE) or PE receiving a variety of anticoagulants/thrombolytics over a 30-90 day time frame.

  • VTE-BLEED – major bleeding after day 30 in patients taking warfarin or dabigatran.

  • REITE – major bleeding within 90 days of anticoagulant therapy with heparin/warfarin.

  • BACS – major bleeding within 30 days in patients who have received systemic thrombolysis.

The PE-SARD bleeding risk score is the first score fully dedicated to assessing bleeding risk in the acute phase of PE – namely during the initial hospitalization.

We should consider bleeding rates when we anticoagulate…
The PE-SARD bleeding risk score was derived from a prospective, multicenter registry. Authors built the score using a post hoc multivariable logistic regression and validated the model internally in the derivation dataset using statistical methods. Similar to the existing bleeding prediction tools, patients in the cohort had received a variety of anticoagulant medications: parenteral (84.7%), direct oral anticoagulants (DOACs) (22.2%), and advanced therapies including thrombolytics (5.3%).

The SARD acronym indicates three predictors identified in the regression analyses, each with a weighted point assignment: Syncope (+1.5), Anemia [hemoglobin <12 g/dL] (+2.5), and Renal Dysfunction [eGFR <60mL/min] (+1). Patients within the point score model (0-5) with more points are at greater risk for major bleeding events and classified into risk categories: low risk (0 points), intermediate risk (1-2.5 points), and high risk (>2.5 points).

When dichotomized as low v. intermediate- and high-risk, the PE-SARD improved major bleeding prediction (determined by Harrell’s C-indexes) when compared to VTE-BLEED, RIETE, or BACS. Further, sensitivity analyses showed prediction performances similar across those with or without high-risk PE and patients younger or older than 75.

Another Spoonful
Here is an aside regarding bleeding in acute PE – After an assessment of bleeding risk, choice of anticoagulation matters:

  1. Current guidelines recommend low molecular weight heparin (LMWH) over unfractionated heparin (UFH) in a majority of patients(5). In hospitalized patients, UFH is associated with a ~5x higher bleeding rates when compared to LMWH(6). Remember: only ~5% of patients with PE are high-risk and go on to receive thrombolytic therapy(7). (Per current guidelines, only patients with evidence of hemodynamic instability or cardiovascular collapse are eligible for thrombolytic therapy(5,8). Therefore, ubiquitous administration of UFH in anticipation of the possibility of an emergent procedure is not advisable.

  2. DOACs have lower rates of major bleeding, clinically relevant non-major bleeding, and serious adverse events when compared to warfarin(9-14).

  3. Within the DOAC family, new evidence suggests that new users of apixaban have lower rates of bleeding than new users of rivaroxaban in patients with VTE(15).

How about some dessert?
Check out Klok & Huisman’s review on the assessment of bleeding in patients with VTE published in Blood(16).

An Original Risk Score to Predict Early Major Bleeding in Acute Pulmonary Embolism: The Syncope, Anemia, Renal Dysfunction (PE-SARD) Bleeding Score. Chest. 2021 Nov;160(5):1832-1843. doi: 10.1016/j.chest.2021.06.048.

Works Cited

  1. Klok FA, Hosel V, Clemens A, et al. Prediction of bleeding events in patients with venous thromboembolism on stable anticoagulation treatment. Eur Respir J 2016;48:1369-76.

  2. 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. Thrombosis and haemostasis 2008;100:26-31.

  3. 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. Eur Respir J 2020.

  4. Schulman S, Kearon C, Subcommittee on Control of Anticoagulation of the S, Standardization Committee of the International Society on T, Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. Journal of thrombosis and haemostasis : JTH 2005;3:692-4.

  5. Konstantinides SV, 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). European heart journal 2020;41:543-603.

  6. Cossette B, Pelletier ME, Carrier N, et al. Evaluation of bleeding risk in patients exposed to therapeutic unfractionated or low-molecular-weight heparin: a cohort study in the context of a quality improvement initiative. Ann Pharmacother 2010;44:994-1002.

  7. Laporte S, Mismetti P, Decousus H, et al. Clinical predictors for fatal pulmonary embolism in 15,520 patients with venous thromboembolism: findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry. Circulation 2008;117:1711-6.

  8. Giri J, Sista AK, Weinberg I, et al. Interventional Therapies for Acute Pulmonary Embolism: Current Status and Principles for the Development of Novel Evidence: A Scientific Statement From the American Heart Association. Circulation 2019;140:e774-e801.

  9. Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. The New England journal of medicine 2013;369:799-808.

  10. Investigators E-P, Buller HR, Prins MH, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. The New England journal of medicine 2012;366:1287-97.

  1. Investigators E, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. The New England journal of medicine 2010;363:2499-510.

  2. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. The New England journal of medicine 2009;361:2342-52.

  3. Schulman S, Kakkar AK, Goldhaber SZ, et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 2014;129:764-72.

  4. Hokusai VTEI, Buller HR, Decousus H, et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. The New England journal of medicine 2013;369:1406-15.

  5. Dawwas GK, Leonard CE, Lewis JD, Cuker A. Risk for Recurrent Venous Thromboembolism and Bleeding With Apixaban Compared With Rivaroxaban: An Analysis of Real-World Data. Ann Intern Med 2021.

  6. Klok FA, Huisman MV. How I assess and manage the risk of bleeding in patients treated for venous thromboembolism. Blood 2020;135:724-34.

Reviewed by Clay Smith

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