D-Dimer in Patients at "Intermediate Risk" of Pulmonary Embolism

The Gist: A D-dimer in the evaluation of suspected pulmonary embolism (PE) in patients with an intermediate probability of PE is recommended in many professional society guidelines [1-4]. The intermediate probability group is the most high-value group for application of a D-dimer, particularly in places such as the United States where the prevalence of PE among those tested is typically <10% [5].

Risk stratification of pulmonary embolism is complex, partially due to the presence of several cut-offs in Wells, one of the most popular risk stratification scores in the United States [6].

The origin: The original Wells score used a trichotomized risk scoring system: Low (<2), Intermediate (2-6), and High (>6), however, this was prior to the introduction of computed tomographic pulmonary angiogram (CTPA) and used compression ultrasound and ventilation-perfusion (V/Q) scans [7]. The diagnostic alogrithm proposed by Wells in 2001 was complex yet many patients in the intermediate-risk group who had a negative d-dimer were considered to have PE excluded (all of these patients got a V/Q and then high probability V/Q scans were treated as positive for PE regardless of dimer result) [78]. Further, this iteration employed a D-dimer assay not widely used currently (SimpliRED), a qualitative assay rather than the high sensitivity quantitative assays [8,9].

The simplification: The initial Wells algorithm was cumbersome and quickly became outdated with CTPA and new d-dimer assays. In 2006, the Christopher Study, evaluated a dichotomized Wells Score that stratified patients into "PE likely" (Wells >4) or "PE Unlikely" (Wells ≤ 4). This study incorporated more relevant diagnostic tests, the CTPA and the VIDAS or Tinaquant quantitative D-dimer assays and found that "PE unlikely" patients with a negative D-dimer had very low risk of PE at 90 days (0.5%; 95%CI 0.2%-1.1%). Approximately 37.1% had PE in the "PE likely" group vs 12.1% in the "PE unlikely" group [10].

The "intermediate" risk group incorporates patients for whom the D-dimer is the most helpful. Evaluation patterns for suspected PE vary across the world; however, CTPA yield (# positive/#ordered) is particularly low in the United States, generally <10% but often in the 3-5% range [5,11]. In a recent US study the prevalence of PE was 4% and, contrasted with the aforementioned Christopher study, in which the overall prevalence of PE was 20%, demonstrates that in the US the patients we evaluate are at even lower risk of PE. Thus, in the US, the dichotomized Wells score likely moves patients with a probability of PE <15-20% to the "PE likely" group, inflating their perceived risk of PE.

In the US, we have a problem with overtesting for PE, and the use of the D-dimer in the intermediate-risk group, in addition to clinically adjusted D-dimer thresholds, may help improve the quality of care we deliver to patients [12].

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D-Dimer in Patients at "Intermediate Risk" of Pulmonary Embolism