D-Dimers

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Figure 1. Generation of D-dimers. D-dimer molecules are generated through the degradation of crosslinked fibrin during fibrinolysis. s. D-dimer generation requires the activity of three enzymes: thrombin, activated factor XIII (factor XIIIa), and plasmin. First step is thrombin-mediated conversion of soluble fibrinogen to fibrin monomers. The fibrinogen molecules consist of a central E domain linked by coiled-coil regions to 2 peripheral D domains. To form fibrin monomers, thrombin cleaves short peptides (fibrinopeptides) from the N-terminal domain of the alpha- and beta-chains to expose “knobs” in the E domains (not shown). Second step is spontaneous polymerization end to end in a half-staggered, overlapping manner to form double-stranded fibrin protofibrils (the exposed knobs in the E domains insert into pre-existing “holes” in the D domains). Because the monomers and protofibrils are associated noncovalently, the fibrin network is unstable. Third step is factor XIIIa-mediated cross-linking of the D domains of adjacent fibrin monomers. Fourth step is plasmin-mediated degradation of of the fibrin network into soluble fragments, including DD(E) and DD. The presence of D-dimer molecules is suggestive of intravascular coagulation because it can only be generated after thrombin formation and subsequent degradation of cross-linked fibrin.

D-dimer assay:

  • D-dimer is detected and quantified in whole blood, plasma, or serum using monoclonal antibodies that recognize a specific epitope on cross-linked D-dimer molecules that are otherwise absent on the D-domain of fibrinogen and fibrin monomers that are non-cross-linked.
  • > 30 commercial D-dimer assays are available, including
    • Enzyme-linked immunosorbent assays (ELISA)
    • Immunofluorescent assays
    • Latex agglutination assays
Figure 2. Reference
Source: Am J Hematol. 2019;94:833-839.

Source: Am J Hematol. 2019;94:833-839.

Clinical uses of D-dimer:

  • Exclusion of venous thromboembolism
Source: Am J Hematol. 2019;94:833-839.
  • Assessment of the duration of anticoagulation
  • Diagnosis of disseminated intravascular coagulation
Source: Am J Hematol. 2019;94:833-839.
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