D-dimer testing: advantages and limitations in emergency medicine for managing acute venous thromboembolism

Abstract

Patients with suspected deep vein thrombosis (DVT) or pulmonary embolism (PE) are frequently admitted to an Emergency Department (ED) for initial evaluation. However, management of patients with suspicion of acute venous thromboembolism (VTE) in this clinical setting can be difficult; in fact symptoms and signs of DVT are non-specific and can be found in a broad spectrum of non-thrombotic disorders. An accurate and timely objective diagnosis is necessary for immediate and correct identification of patients with acute VTE, while avoiding the bleeding risk associated with unnecessary anticoagulant therapy in patients where DVT or PE have been ruled out. The diagnostic approach to patients with suspected VTE includes clinical evaluation, diagnostic imaging and D-dimer testing [1, 2]. In a recent issue of Internal and Emergency Medicine, Siragusa [3] exhaustively discussed the currently used assays, clinical indications and limitations of D-dimer testing for managing acute VTE in emergency medicine. Measurement of D-dimer values, a degradation product of cross-linked fibrin, is a simple laboratory test, and has been extensively studied in numerous prospective cohort studies in cases of suspected DVT or PE, showing a high negative predictive value. The author [3] shows that D-dimer testing has sufficient diagnostic accuracy for ruling out acute VTE if used in combination with standardised clinical judgement. The review is important for at least three reasons. First, many physiological and pathological conditions can increase plasma D-dimer levels (pregnancy, age, trauma, cancer, inflammation and several other clinical conditions); on the other hand D-dimer levels may fail to increase in patients with acute VTE for multiple reasons (impaired fibrinolytic activity, use of heparin or oral anticoagulants, onset of symptoms more than two weeks before blood sampling). For these reasons, D-dimer testing has a high sensitivity but a low specificity in the diagnosis of acute VTE; in clinical practice it may be associated with frequent “false positive” results, but also more rarely with “false negative” findings. However, its use should always be associated with a careful clinical assessment to rule out the presence of acute VTE only in symptomatic patients. Overuse or misuse of the D-dimer screen for VTE may have negative consequences, in terms of a burden both for patients and for healthcare costs; in fact, despite clinical guidelines, inappropriate and unnecessary measurement of D-dimer is a significant clinical problem [4]. Second, commercially available assays are very differ