ABSTRACT
In the course of fibrin formation, the D-domains of adjacent fibrin molecules within
the fibrin polymer are covalently linked by factor XIIIa, leading to the formation
of a D-domain dimer. Proteolysis of this cross-linked fibrin generates fibrin fragments
D-dimer and E as terminal products. Fragment D-dimer therefore is an indicator for
the proteolysis of cross-linked fibrin, whereas the monomeric fragment D can stem
from fibrinogen and non-cross-linked fibrin. Various monoclonal antibodies have been
prepared that distinguish between fragments D-dimer and D and allow the detection
of fibrin derivatives in the presence of fibrinogen. These anti-D-dimer-antibodies
have been shown to react with fragment D-dimer, but also detect dimeric D-domains
within larger fibrin compounds, including cross-linked fibrin complexes generated
in an early phase of coagulation activation. Assay systems for D-dimer antigen therefore
may uncover intravascular clot formation early, by detection of fibrin complexes,
and after completion of clot formation, by the detection of proteolytic fragments
released from the particulate clot. Various trials have shown that low concentrations
of D-dimer antigen in the blood 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 systems
include manual immunoagglutination assays, immunofiltration assays, microtiter plate
enzyme-linked immunosorbent assay (ELISA) systems, automated ELISA systems, and latex-enhanced
photometric immunoassays. According to clinical studies, D-dimer assays may be the
``first line'' of technical screening in symptomatic outpatients with suspected venous
thrombosis or pulmonary embolism, but further prospective management trials, and improved
standardization of assay systems, are needed for the validation of this approach.
KEYWORD
D-dimer - venous thrombosis - pulmonary embolism - assay systems - outpatient diagnosis
