Pulmonary Embolism Risk Stratification and Thrombolysis

When it comes to pulmonary embolism (PE), making the diagnosis is often the most difficult part.  Treatment is usually straightforward – SQ or IV anticoagulation.  Sometimes, though, the patient is really ill and needs more aggressive intervention.

It’s important to risk stratify your PE patients in order to determine if your patient meets criteria for thrombolysis (or emergency surgery if lytics are contraindicated).  Some people may feel like this is the consultant’s call and beyond the scope of the ED care, but I disagree with this philosophy when it comes to critical patients, particularly when the interventions are within our capabilities.  If my patient is dying, and needs something I can deliver, I want it to happen right now, in the ED.  This is the situation with some PE patients.

Fortunately, most of the PEs we see aren’t associated with high-risk features and can be treated simply with full dose heparin (or other anticoagulants).  There does not appear to be any clinical benefit to using IV heparin, so low-molecular-weight heparin would seem the preferred choice for these patients due to its ease of use and predictability.

Traditionally, sicker PE patients were divided into massive or submassive PE, but in order to figure out which patients will benefit from thrombolytic therapy, the submassive category is further divided by high risk and low risk features.

Massive PE is rather straightforward.  These patients are hemodynamically unstable.  Although actual trial data are limited, we know from experience that these patients need thrombolytics and heparin unless strong contraindications are present.  In that situation, a cardiovascular surgeon should be immediately consulted for surgical embolectomy.  Alteplase (tPA) is FDA approved for PE at a dosage of 100 mg IV over 2 hours.  Tenecteplase (TNK) is used in some studies at the usual weight-based dosage used for MI.

Submassive is defined as having evidence of “Right Ventricular (RV) dysfunction” on ECHO.  This is not a minor distinction so an ECHO is worth pursuing in patients that have abnormal vitals signs, appear ill, or have significant symptoms.  10% of these patients will progress to hemodynamic shock (massive PE), and half of those will die.  Although most of the PE patients we treat are low risk, we need to respect the significant risk of death when the patient is under cardiovascular strain.

Recent studies have examined the survival benefit of thrombolysis for patients in the submassive category, and are finding that those with high-risk features do have a significant benefit from thrombolysis.  We should know these so we can provide optimal treatment for our patients.

In the PEITHO trial (Pulmonary Embolism Thrombolysis, NEJM, April 10, 2014), all submassive PEs were grouped together to study TNK with heparin, and the rate of death or hemodynamic deterioration was 5.6% in the control group vs. just 2.6% in the treatment arm.  However, there was a 6% rate of bleeding, including 2% with intracranial hemorrhage.  The current thinking is to optimize this therapy by targeting the high-risk patients that will benefit and minimize the exposure to low-risk patients that may not need it.

High-risk features of submassive PE include:

  • abnormal vital signs
  • elevated BNP or troponin (as a marker of heart strain)
  • severe RV hypokinesis on ECHO (right ventricle has failed)
  • ill-appearing clinically (which is your judgment at the bedside)

The idea that these patients do better with thrombolysis makes sense, because these patients are already failing under the current clot burden but just haven’t crashed to frank hemodynamic instability yet.  The patients without these features are adequately compensating.  These patients are likely at lower risk of mortality and therefore giving thrombolytics exposes them to potential harm without clear benefit in terms of survival.  Some specialists in the field argue that thrombolysis is worth the risk in all of these patients to minimize the long-term complications of recurrent episodes and pulmonary hypertension, which can have dire consequences.  I think that decision is beyond my scope in the ED, but not the decision to give thrombolytics to my high-risk submassive PE patient.

Recent studies have demonstrated improved hemodynamics and other surrogate outcomes in the high-risk submassive PE population, but have been too small to demonstrate a significant mortality benefit.  One interesting study tested half dose tPA (50 mg) in this group of patients.  It also was too small to show a mortality benefit, but showed a huge decrease in pulmonary hypertension (16% to 0.5%).  The interesting part is that there were no bleeding complications.   Hopefully, lower doses are being studied in acute stroke as well.

When it comes to PE patients, the clinical condition really dictates the treatment.  For critically ill patients with PE, or presumed PE, full dose thombolytics should be given. You may have a patient that you already know has a PE that then deteriorates, and those patients should have thrombolysis initiated unless absolute contraindications exist.

If your patient with PE has normal vitals and seems fine clinically, then you can just anticoagulate by your preferred method.  Although an ECHO is indicated to further stratify these patients, I don’t think you would need to get the ECHO urgently since they don’t meet criteria for thrombolysis anyway.

For patients with abnormal vitals, abnormal troponin or BNP, or with significant symptoms, you should obtain an ECHO to further evaluate their RV function, and make preparations to give thrombolytics.  These patients are at high risk for deterioration and you may need to escalate therapy accordingly.

These cases are fortunately rare, so I’d love to hear from you if you have had personal experience with massive or submassive PE and giving thrombolytics.

Marc Futernick, MD, FACEP
ED Medical Director
California Hospital Medical Center, Los Angeles, CA
Chair, VEP Board of Directors
[email protected]

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