D-dimer

Principle

• D-dimer is a degradation product released when plasmin breaks down cross-linked fibrin (stabilised by factor XIIIa). Its presence shows that both coagulation and fibrinolysis have occurred.
• Detected using monoclonal antibodies against the D-dimer epitope, which do not react with fibrinogen or non-cross-linked fibrin products.

Specimen

• 3.2% sodium citrate plasma (some point-of-care methods use whole blood).

Procedure

• Methods in use:
• Latex agglutination (semi-quantitative, slide).
• ELISA and enzyme-linked fluorescent assays (high sensitivity, reference methods).
• Latex-enhanced immunoturbidimetric assays on coagulation analysers (rapid, quantitative, most common).
• Whole-blood point-of-care agglutination.

Results

• Units differ between kits: fibrinogen equivalent units (FEU) or D-dimer units (DDU); a result in FEU is roughly twice the same result in DDU. Always report units and method.
• A commonly used cut-off for excluding VTE is 0.5 mg/L FEU (500 ng/mL FEU), but it is assay specific.
• Age-adjusted cut-off in patients over 50 years: age × 10 µg/L FEU.

Interpretation

• Main value is a high negative predictive value: a normal result with low or intermediate clinical probability (e.g. Wells score) helps exclude DVT or PE.
• Raised in DVT/PE, DIC, surgery, trauma, pregnancy, malignancy, infection, inflammation, liver disease, older age and after thrombolysis; a positive result is not specific.

Quality control and pitfalls

• False negatives: small or distal clots, long-standing thrombus, anticoagulant therapy.
• Heterophile antibodies and rheumatoid factor can interfere with immunoassays; severe lipaemia, haemolysis or icterus may affect turbidimetric methods.
• Very high values may need dilution (hook effect in some assays).
• Run normal and abnormal controls with each batch.

Clinical use

• Exclusion of VTE, diagnosis and monitoring of DIC (part of the ISTH score).