Internal Medicine Society of Australia and New Zealand

The D-dimer test is highly sensitive for deep vein thrombosis and pulmonary thromboembolism, such that a negative result in non-pregnant adults (adjusted for age) rules out this condition in patients with low pre-test probability. A positive result is however non-specific and may be due to many other conditions apart from PTE. In ruling out PTE, D-dimer assay should be the first choice investigation in patients classified as being low risk according to the Wells’ score (equal to or less than 4).

These considerations are heightened by the risks associated with CTPA testing such as radiation exposure and incidental imaging findings, e.g. lung nodules and adrenal lesions that may provoke further investigations and diagnosis of isolated small subsegmental emboli whose natural history is unknown and for which anticoagulation is not yet shown to be of benefit. There is, however, a 1 – 3% failure rate with a low risk Wells’ score and negative D-dimer prediction method, so close follow-up is indicated in all patients in whom a D-dimer has been requested. Note that laboratories do not report age adjusted values, though it is well known that D-dimer levels rise with age in the presence of co-morbidities.

An example of age adjustment, endorsed by the clinical guidelines committee of the American College of Physicians (see reference from Raja et al below) quotes a upper limit of normal for D-dimer tests equal to age × 10 ug/L, rather than a generic upper limit of of 500 ug/L. Clinical judgement is necessary in applying this adjustment method, with some reports adopting a more conservative formulae of age x 5 ug/L.

Modified Wells score (mWS) of ≤4 = low risk patients, >4 = high risk patients

Reference: Wells PS, Anderson DR, Rodger M, Ginsberg JS, Kearon C, Gent M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost. 2000:83 (3): 416–20.

Note: D-dimer is routinely elevated from the first trimester and gestational age normative D-dimer levels have not been sufficiently validated to allow their use as a risk stratification tool in pregnancy. Most pregnant women with no clinical evidence of DVT will have negative lower limb venous Doppler as pulmonary emboli originate in the pelvic veins, which are not accurately evaluated with duplex compression Doppler ultrasound. In such cases, ventilation perfusion lung scanning is the test of choice, due to lower breast dose than CTPA in pregnant women with suspected pulmonary embolism provided chest radiograph is normal and an alternative diagnosis such as neoplasia or aortic dissection, that are detectable with CT and not with VQ, is not suspected.

Supporting evidence

• Carrier M, Righini M, Wells PS, et al. Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies. J Thromb Haemost 2010; 8:1716-22.
• Ong CW, Malipatil V, Lavercombe M, et al. Implementation of a clinical prediction tool for pulmonary embolism diagnosis in a tertiary teaching hospital reduces the number of computed tomography pulmonary angiograms performed. Intern Med J 2013; 43(2):169-74.
• Pasha SM, Klok FA, Snoep JD, et al. Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: A meta-analysis. Thromb Res 2010; 125:e123-7.
• van Es N, van der Hulle T, van Es J, et al. Wells rule and D-dimer testing to rule out pulmonary embolism. A systematic review and individual-patient data meta-analysis. Ann Intern Med 2016; 165:253-61.
• Raja AS, Greenberg JO, Qaseem A, et al. Evaluation of patients with suspected acute pulmonary embolism: best practice advice from the clinical guidelines committee of the American College of Physicians. Ann Intern Med 2015; 163:701–11.