D-dimer testing in cardiovascular disease: Laboratory and clinical pitfalls

D-dimer as a mixture of soluble cross-linked fibrin degradation products cleaved by plasmin is a well-established biomarker of in vivo blood coagulation activation with concomitant secondary fibrinolysis that is widely determined in a broad variety of clinical settings. D-dimer interpretation is hampered by the lack of the assay international standard and assay harmonization across laboratories, preanalytical variables affecting the results, multiple assays available with different units, and the impact of heterophilic nonspecific IgG or IgM antibodies, which cause falsely increased or decreased results. Different reactivity of monoclonal antibodies against D-dimer molecule results in a variability of results obtained with different assays within individual patients. Compelling clinical evidence supports a high negative predictive value of age-adjusted D-dimer concentration in ruling out venous thromboembolism, both pulmonary embolism and deep-vein thrombosis. Elevated D-dimer levels are observed in acute myocardial infarction or stroke, aortic aneurysm and acute dissection, atrial fibrillation, heart failure, following invasive procedures, infection. Elevated D-dimer can be found in chronic venous insufficiency, chronic inflammatory diseases, cancer, sepsis, autoimmune disorders, diabetes, advanced age, strenuous physical activity, and pregnancy. Though elevated D-dimer is associated with increased risk of first and recurrent venous thromboembolism, it is no per se indication for anticoagulant treatment and should lead to in-depth diagnostic evaluation to identify mechanisms underlying such abnormality. The current overview summarizes both laboratory and clinical knowledge on D-dimer measurement and interpretation with focus on acute and chronic cardiovascular diseases.