Use of D-dimer assays in the diagnosis of venous thrombosis

In the course of fibrin formation, the D-domains of adjacent fibrin molecul es within the fibrin polymer are covalently linked by factor XIIIa, leading to the formation of a D-domain dimer. Proteolysis of this cross-linked fib rin generates fibrin fragments D-dimer and E as terminal products. Fragment D-dimer therefore is an indicator for the proteolysis of cross-linked fibr in, whereas the monomeric fragment D can stem from fibrinogen and non-cross linked fibrin. Various monoclonal antibodies have been prepared that distin guish between fragments D-dimer and D and allow the detection of fibrin der ivatives in the presence of fibrinogen. These anti-D-dimer-antibodies have been shown to react with fragment D-dimer, but also detect dimeric D-domain s within larger fibrin compounds, including crosslinked fibrin complexes ge nerated in an early phase of coagulation activation. Assay systems for D-di mer antigen therefore may uncover intravascular clot formation early, by de tection of fibrin complexes, and after completion of clot formation, by the detection of proteolytic fragments released from the particulate clot. Var ious trials have shown that low concentrations of D-diner antigen in the bl ood exclude recent venous thrombosis or pulmonary embolism. Elevated levels may be caused by venous thrombotic disease, but also by a variety of other conditions, leading to intra- or extravascular fibrin formation. Assay sys tems include manual immunoagglutination assays, immunofiltration assays, mi crotiter plate enzyme-linked immunosorbent assay (ELISA) systems, automated ELISA systems, and latex-enhanced photometric immunoassays. According to c linical studies, D-dimer assays may be the "first line" of technical screen ing in symptomatic outpatients with suspected venous thrombosis or pulmonar y embolism, but further prospective management trials, and improved standar dization of assay systems, are needed for the validation of this approach.