D-dimer testing in suspected venous thromboembolism: an update

Fibrin is the main thrombus component. Its production being definitely lower in in-patients than in outpatients. is followed by activation of the fibrinolytic system, resulting in plasmin generation and subsequent fibrin lysis (Figure 1). Dissolution of crosslinked fibrin leads to formation of specific degradation products, includMethods for measuring DD in blood ing D-dimer (DD),1 which can be easily detected and The advantages and disadvantages of the various measured in both whole blood and plasma using methods that measure DD in blood are displayed in monoclonal antibodies directed against epitopes Table 1. For clinical use in emergency situations, located in the DD fragment. In the past decade, DD rapid tests are mandatory. Among them, a whole testing has been established as a useful aid in the blood latex test (Simplired, Agen) that gives a diagnosis of venous thromboembolism (VTE).2 The present review updates experience on the use of DD testing for diagnosis of deep-vein thrombosis (DVT) of the lower limbs and pulmonary embolism (PE). Briefly, DD was found in the late 1980s and early 1990s to be highly sensitive (but non-specific) to the presence of VTE where clinically suspected in outpatients. In this population, the negative predictive value of a plasma DD concentration below a certain cutoff (usually about 500 mg/l) was more than 95%, thereby allowing one to rule out the disease in a substantial proportion (about one third) of patients. However, the diagnostic performances were strongly Figure 1. Generation of D-dimer (DD) fragments. Activation of blood coagulation leads to thrombin generadependent upon the assay used, latex tests being tion. Thrombin binds to the fibrinogen central domain definitely less sensitive than the more cumbersome and liberates fibrinopeptides A and B, resulting in fibrin enzyme-linked immunosorbent assays (ELISA), which monomers and polymer formation. The fibrin network is in turn were not suited for emergency use.2 Moreover, subsequently stabilized (‘cross-linked’) under the effect of this heterogeneity of tests raised uncertainty among activated coagulation factor XIII. Plasmin induces lysis of clinicians, who called for rigorous evaluation and cross-linked (X-linked) fibrin, resulting in formation of standardization of the various assays.3 Lastly, the various X-linked fibrin degradation products (FDPs) includutility of the measurement was dependent on the ing D-dimer (DD) and fragments containing the DD epitope. population to which it was applied, the specificity