A clot in the lungs! And you are too nonspecific! You give D-dimers a bad name.

This is part of a recurring series examining landmark articles in Emergency Medicine, in the style of ALiEM’s 52 Articles.

Discussing: Wells, P., Anderson, D., & Rodger, M. (2001). Excluding Pulmonary Embolism at the Bedside Without Diagnostic Imaging: Management of Patients With Suspected Pulmonary Embolism Presenting To the Emergency Department By Using a Simple Clinical Model and D-dimer. Annals of Internal Medicine, 135(2), 98–107.

 

Main Points: Wells’ scoring system for risk of PE, when combined with a negative D-dimer, is useful to rule out patients unlikely to have significant illness from PE within the next 90 days.

  1. This scoring system combined with D-dimer measurement does not accurately identify patients who are likely to have PE at this encounter or subsequent encounters.

 

Background: Pulmonary embolism (PE) is a common disease (CDC estimates for 2015 are up to 1 in 1,000 persons) and half of patients with PE are not properly diagnosed in the ED due in part to non-diagnostic results of a V/Q scan. This reality presents a diagnostic challenge to ED physicians who are determining which patients should receive a CT scan, and risk stratifying patients for a PE. This study sought to validate the Wells’ Criteria  for determining pretest probability of pulmonary embolism in the ED population.

 

Methods: This was a prospective cohort study of consecutively recruited ED patients at four medical centers in Canada from September 1998 to September 1999. The authors excluded patients with upper extremity deep vein thromboses (DVTs) as the likely source of PE, patients who were symptom free for three days prior to presentation, those who had been on anticoagulation for 24-hours prior to presentation, patients who were not expected to live more than three months after presentation, or anyone who could not get IV contrast, was pregnant, lived too far away for follow-up, or was younger than 18 years of age.

Included patients were risk-stratified by ED physicians based upon the follow criteria:

  1. Objective clinical signs and symptoms of DVT (swelling and pain over deep vein region, 3 points)
  2. HR > 100 BPM (1.5 points)
  3. Immobilization (bed rest, except for using the bathroom, for more than 3 days) or surgery within the past fours weeks (1.5 points)
  4. Previously diagnosed DVT or PE (1.5 points)
  5. Hemoptysis (1 point)
  6. Malignancy (current diagnosis, diagnosis within the last six months, current chemo or palliative care. 1 point)
  7. PE as the most likely, or equally likely diagnosis (based upon clinical gestalt, 3 points)

A patient with a total score of less than 2 was considered low risk, 2-6 was moderate risk, more than 6 was considered high risk. Each patient’s D-dimer level was then measured, and he or she was evaluated for PE based upon an algorithm that can be found in the article (Figure 1). The evaluation included V/Q scan, bilateral lower extremity ultrasound, and/or pulmonary angiogram based upon risk stratification, D-dimer level, and imaging results.

All participants followed-up at 90 days via phone or in-person to recount events that occurred since the initial encounter.

 

Results: The data from 930 patients (average age of 50.5 years) were analysed, with prevalence of PE at 90 days found to be 9.5%. PE was diagnosed in 40.6% of patients with high pretest probability, 16.2% in moderate pretest probability group, and 1.3% in the low pretest probability group. These results indicate the negative predictive value of the d-dimer to be 97.3% in the entire cohort, and 99.5% in the low probability group, 93.9% in the moderate probability group, and 88.5% in the high probability group. In this study the Wells’ criteria/D-dimer model demonstrated poor positive predictive value because it only found PE in 16.9% of patients that were indicated to have any level of image testing (V/Q scan, DVT ultrasound, or angiography based upon the algorithm above). Seventeen patients (0.6%) who had PE and DVT ruled out based upon this model had suspicious events for PE or DVT on follow-up, with five of those events confirmed to be a PE or DVT.

 

While 17 people died during this study, none of the patients who had PE ruled out by the model died from a PE within 90 days of their initial presentation to the ED.

 

Points to consider:

  • Ten percent of the patients enrolled in the study did not have the protocol followed exactly, which limits the external validity of the study.
  • There were no imaging tests performed on the low-risk patients, so we cannot accurately say that they did not have a PE, only that they had a low risk of clinically meaningful event over the subsequent 90 days (either diagnosed PE or death).
  • This study used the more specific SimpliRED D-dimer rather than the traditional immunoassay linked D-dimer thus decreasing the sensitivity of this model compared to the traditional D-dimer assay.

 

Further Study: Only 17% of patients who ruled in for testing were found to have a PE, so there is clearly room to increase the positive predictive value of this tool. Fortunately there have been a number of subsequent studies that have tested methods to increase the specificity of this model, and we have included citations to a few of those studies in the related articles below.

 

Level of Evidence:

ACEP Clinical Policy Grading Level IIB

 

Surprises:

  1. V/Q scan was the test that was used to determine presence or absence of PE, and the current standard is CTPA as it is a more reliable test.
  2. SimpliRED D-dimer was used in this study, not the traditional immunoassay linked D-dimer, which may affect how this criteria applies to patients your department.
  3. Low risk patients got no V/Q scan, so we cannot be sure of actual incidence of PE in these patients, though they were followed up on so we do know there are few risks to not testing these patients for PE.

 

Relevant articles:

Simplification of the revised Geneva score for assessing clinical probability of pulmonary embolism: http://archinte.jamanetwork.com/article.aspx?articleid=414578

 

Performance of 4 Clinical Decision Rules in the Diagnostic Management of Acute Pulmonary Embolism: A Prospective Cohort Study: http://annals.org/article.aspx?articleid=746965

 

Diagnostic accuracy of D-dimer assay in suspected pulmonary embolism patients: http://ac.els-cdn.com/S0422763813003166/1-s2.0-S0422763813003166-main.pdf?_tid=4ce51214-6b05-11e5-9303-00000aacb35d&acdnat=1444010801_80598bd9006f6434671a010c02d76997

 

Source Articles:

Wells, P., Anderson, D., & Rodger, M. (2001). Bedside Without Diagnostic Imaging: Management of Patients With Suspected Pulmonary Embolism Presenting To the Emergency Department By Using a Simple Clinical. Annals of Internal Medicine, 135(2), 98–107.

ACEP Clinical Policy Committee. (2003). Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting With Suspected Pulmonary Embolism. Annals of Emergency Medicine, 41(2), 257–270.

Anderson, D. R., & Barnes, D. C. (2009). Computerized tomographic pulmonary angiography versus ventilation perfusion lung scanning for the diagnosis of pulmonary embolism. Current Opinion in Pulmonary Medicine, 15(5), 425–429.

2 thoughts on “A clot in the lungs! And you are too nonspecific! You give D-dimers a bad name.

  1. Wow. Really interesting. Some points that struck me:

    They excluded patients who were symptom free for the prior three days or who were anticoagulated. I’ve definitely dimered a lot of these patients using the Wells…

    A really poor positive predictive value! I’m sure most people assumed (or knew) this though. I guess the categorizations of “low, moderate, and high probability” threw me off, when in reality even high probability patient’s have an 89% chance of NOT having a PE.

    Patient’s with different risks got different workups. Not only that, but V/Q scan was the preferred study, versus what we use now (CT PE for everyone), which still isn’t technically gold standard. Good luck interpreting whether your high risk patient with a V/Q scan of low or intermediate probability has a PE…

    The d-dimer assay was less sensitive than ours.

    Should we even be applying this tool in our clinical practice??

    I’m also curious to know of the five patient’s that were found to have PE’s (after being ruled out) were low, moderate, or high risk patients (and what sort of imaging they may have had in their initial workup).

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