Prediction of Early Major Bleeding in Acute PE

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.

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