Age-adjusted D-dimer Cut-off to Rule Out Pulmonary Embolism in the Emergency Department : A Real Life Impact Study

BACKGROUND

PE diagnostic strategies Pulmonary embolism (PE) is a frequently suspected diagnosis in the emergency room (ER) in patients presenting with shortness of breath and/or chest pain without any obvious cause identified. Historically, PE diagnosis required a pulmonary angiography, a costly and invasive procedure with associated morbidity and even mortality. Over the last 25 years, evolving diagnostic strategies have been developed and widely validated in prospective multicentre management outcome studies, with the aim of confirming or excluding the diagnosis of PE safely enough to avoid realising pulmonary angiography. Nowadays, PE diagnosis therefore relies on diagnostic strategies, including sequential evaluation of clinical probability, measurement of plasma D-dimer levels and most often CT pulmonary angiogram (CTPA), rather than a standalone test.

The initial and essential step is the assessment of pre-test clinical probability, either by gestalt or by validated clinical prediction rules (Wells rule of Geneva score). This initial evaluation separates patients into different groups of PE prevalence, and thus directly influences the negative and positive predictive values of the diagnostic tests used in these patients.

D-dimer measurement Plasma D-dimer measurement has been extensively evaluated for the exclusion of PE in outpatients. The diagnostic usefulness of D-dimers lies in their high sensitivity and hence their capacity to exclude PE when below a certain cut-off ("negative D-dimers") without further investigations. Indeed, in patients with "non-high" clinical probability (low and intermediate groups in a three category score or unlikely group in a dichotomic score), a highly sensitive negative D-dimer test safely excludes PE without additional investigations. Sensitive D-dimer tests include those performed by the ELISA technique (median sensitivity 99%; Vidas®, Stratus®, AxSYM®) and by quantitative latex methods (median sensitivity 96%; STA Liatest®, Tinaquant®). In patients with high clinical probability or likely PE, the negative predictive value of even a highly sensitive D-dimer test will be insufficient to exclude PE. D-dimer measurement is thus not used in these patients.

Performance of D-dimers in elderly patients The specificity of the ELISA and quantitative latex D-dimer tests for venous thromboembolism (VTE) is limited, ranging from 35 to 40%. Indeed, D-dimers increase in various clinical situations, including cancer, infectious or inflammatory states, pregnancy or during post-operative periods, but also with age, leading to reduced specificity of the test in elderly patients. In other words, the probability of having a negative test result is reduced, so that the number of patients needed to test (NNT) to exclude one PE without further investigations is higher. Indeed, whereas PE can be ruled out in presence of non-high clinical probability and negative D-dimers in one out of 3 outpatients presenting to the emergency room with suspected PE, it can be excluded in only one out of 20 patients > 80 years. As current diagnostic strategies for PE include imaging (most often CTPA) in patients with positive D-dimers, lack of specificity of D-dimers in the elderly leads to a high proportion of these patients undergoing CTPA.