April 10th, 2017
Pulmonary Embolus: Evaluating the Five Ps of PE
Years ago, my physician father said to me; “If something does not make sense, if you struggle to determine the pathology, consider pulmonary embolus (PE).”
More recently, an ER physician colleague offered me the following advice: “If you think about PE, test for it.”
Of course, an astute clinician places both pieces of wisdom into context. I am not going to look for PE in patients presenting with ambiguous abdominal pain nor am I going to order d-dimers on all patients with a hint of PE. I also accept that tucked in the fables and parables of medicine are certain truths that deserve my attention. The first piece of advice speaks to the cryptic and non-specific presentation of pulmonary embolus and the second refers to the importance of clinical suspicion or gestalt.
The mortality, morbidity, and prevalence of PE combined with its enigmatic presentation can cause trepidation and uncertainty in providers, sometimes triggering haphazard or inappropriate testing. Such testing may result in poor outcomes for patients (and providers). Moreover, the confusion is compounded by conflicting opinion and divergent practice: some providers never order a d-dimer, some order one on every low-risk patient, some start with CTA, etc. If I ask three clinicians about their work-ups, I will likely get three quite different answers. Furthermore, anecdotes are powerful; we all have stories about the most unlikely presentation of PE. Consequently, PE evaluation can be as murky and off-putting as my grandmother’s pea soup (sorry, grandma). Nonetheless, even though PE is a pernicious, petulant and peculiar pathology, we can find clarity if we carefully consider the five Ps of PE evaluation. What is more – you can count them on the phalanges of one hand.
P1. Patient Presentation
Step one: look at your patient. Prior to any testing, perform a thorough history and physical. Patients with PE present in a variety of ways and symptoms can be subtle. Symptoms of PE include: dyspnea, pleuritic chest pain, cough, syncope, hemoptysis, tachycardia, fever, leg swelling. Dyspnea and chest pain are the most common symptoms of PE; however, neither is sufficiently sensitive or specific to rule pulmonary emboli in or out.
P2. Pre-test Probability
Step two: determine pre-test probability. You can use either your gestalt or validated clinical prediction rules to further stratify risk in your patient. My preference is to use a combination of the two, as my years in medicine have taught me two facts: firstly, my judgement is fallible, and secondly, some patients do not fit the rules. Knowing in medicine is never a simple algorithm or a score; it is a shared multidimensional process that transcends these.
P3. Prediction Rules
Step three: prediction rules. Well validated clinical prediction tools include the revised Geneva (rGeneva) and the two-step Wells’ scores.1 The rGeneva score is entirely objective. Patients are stratified in low, intermediate and high risk. The two-step Wells’ score divides patients into PE unlikely (≤4) and PE likely (>4). The criticism of the Wells’ score is that it incorporates clinical gestalt by giving 3 points for suspicion for PE. Both scores guide subsequent testing. A patient who is <50 years old and is considered low risk by gestalt or prediction tool can be further ruled out by using the Pulmonary Embolism Rule Out Criteria (PERC).
Undoubtedly, given the variability in use and inconsistent knowledge of these rules, serious consideration should be given to incorporating clinical decision tools (as computer support aids) in electronic charting, especially for providers who are inexperienced or risk-averse, or who infrequently stratify PE risk. These aids do not usurp gestalt but rather enhance it.
Step four: the d-dimer. Patients who don’t meet PERC should be further stratified by the plasma d-dimer, a fibrin degradation product that when present indicates the initiation of procoagulant and fibrinolytic pathways. D-dimers may rule out PE in low-risk and even moderate-risk patients, depending on the assay used. Remember, they are sensitive but not specific. Moreover, do not order d-dimers on high-risk patients as the increased incidence of disease in these patients creates spectrum bias (if you change the patient case mix, you change the performance of a test).
Different assays are available and have different cutoffs and units. A common and sensitive d-dimer assay is the ELISA. Another sensitive assay is the immunoturbidimetric. Both are quantitative. One of my practice sites uses the former and the other uses the latter. If you plan to age adjust the d-dimer you must know the following i) the type of assay, ii) the reporting unit, and iii) the cutoff. If you don’t know these things, you could make critical errors.
The greatest use of the d-dimer stems from its high negative predictive value. Thus the d-dimer is for patients who are “PE unlikely” by Wells (≤4) or gestalt but are not ruled out by PERC. The ELISA d-dimer assay can also be used in conjunction with clinical prediction tools to rule out patients with intermediate risk.
Age adjusting the d-dimer to further stratify risk and reduce unnecessary imaging while maintaining sensitivity is a hot topic. The American College of Physicians recommends using age-adjusted d-dimer thresholds (age x 10 ng/ml) rather than a generic cutoff to determine d-dimer elevation in patients older than 50 years. Most faculty I asked stated that they would support use of age-adjusted d-dimers in PE algorithms, despite some doubts regarding population cohorts, gold standards, and variant assays. If you want to delve further into the potential problems and pitfalls of the d-dimer, Rory Spiegal MD, provides an interesting discussion of these in his blog EMNERD.
I consider some practices to be poor: for example, ordering d-dimers in triage. Typically, triage is not conducive to a thorough exam nor does it give time for accurate risk assessment; such profligate ordering might incite the wrath of your colleagues. I made this error myself as a new grad PA in triage. Lesson learned. If you see this, kindly put the kibosh on it. Furthermore, the d-dimer isn’t a lab you order and then fail to follow up. Just don’t do it. Indiscriminate use of the d-dimer jeopardizes the safety of your patient whereas judicious use protects your patient.
Step 5: Imaging studies. Patients with a positive d-dimer or high pre-test probability require imaging studies. The gold standard is the CTA PE. This test is not innocuous. It may detect subclinical PEs, result in contrast-induced nephropathy, cause allergies, and create a financial burden for the patient. However, in the high-risk patient, the CTA is the go-to test. VQ scanning is useful for patients with contraindications to CT but not for patients with CHF, COPD or pneumonia. Another valid strategy is to order venous duplex studies of the lower extremities prior to CT as this may eliminate the need for CT and obviate its inherent risks.
In conclusion, pernicious, petulant, and peculiar is as pernicious, petulant and peculiar does; yet by paying attention to the Ps of PE evaluation, you can improve outcomes, reduce cost, sharpen your skills as a diagnostician, and enjoy your own brand of P soup.
Douma RA et al. Prometheus Study Group. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism: a prospective cohort study. Ann Intern Med. 2011; 154:7009.