Normal blood D-dimer concentrations: do they exclude pulmonary embolism?

Background Although pulmonary embolism (PE) with normal blood D-dimer (DD) concentrations is considered rare, in practice the incidence may be greater than is generally believed. Overlooking PE is potentially dangerous. The aim of this study was to explore the incidence and clinical features of PE with normal DD concentrations. Methods We retrospectively analyzed the records of 29 patients with PE and normal DD concentrations from the past seven years. We here compare relevant clinical characteristics of these patients with those of patients with PE and abnormal DD concentrations. We evaluated the probabilities of differences by computing pretest probability scores (Wells score and revised Geneva score). Results The frequency of normal DD concentrations in patients with PE was 4%. Previous episode(s) of PE were more common in patients with normal DD concentrations than in those with abnormal DD concentrations (P=0.001). Fever, tachycardia, and tachypnea occurred less frequently in the former group (P<0.05) and time between onset of symptoms and DD testing was longer (P=0.001). The diagnosis of PE was delayed in 22 of the 29 cases. Nineteen and seven cases with normal DD concentrations were classified according to pretest scores as intermediate and low risk, respectively. Conclusions PE with normal DD concentrations is uncommon. Although most diagnoses of PE are ruled out by normal DD values, a small number of cases with PE are missed. A combination of pretest probability score and normal DD concentration increases the probability of making the correct diagnosis, but cannot completely exclude patients with suspected PE. When the clinical manifestations cannot be otherwise explained, clinicians should be alert to the possibility of PE with normal DD concentrations in patients with previous episode(s) of PE or a long interval between onset of symptoms and DD testing.