Deep venous thrombosis and
pulmonary embolism represent two expressions of a similar clinical pathological process traditionally referred to as
venous thromboembolism. Several population studies evidence
venous thromboembolism as a leading healthcare problem worldwide, highlighting the need for early and reliable diagnosis to enable appropriate triage of affected patients and to optimize outcome. There is still debate, however, on which thrombotic markers to use, as well as their most suitable position within diagnostic algorithms. This article aims to review the pathophysiology and clinical usefulness of past, present and future markers of
thrombosis, including soluble
fibrin monomers,
fibrin/fibrinogen degradation products,
thrombin-antithrombin complex,
plasmin-
antiplasmin complex,
fibrinopeptide A and B,
prothrombin fragments 1 + 2,
thrombus precursor
protein,
D-dimer, activated
protein C-
protein C inhibitor complex,
myeloperoxidase,
thrombin generation assays and proteomic analysis. Several lines of evidence now attest that the global diagnostic performances of some
D-dimer assays largely outperform those of any other coagulation or fibrinolytic marker proposed thus far, and a "negative"
D-dimer measured with rapid
enzyme linked fluorescent immunoassay is now considered the biochemical gold standard for ruling out an acute episode of
venous thromboembolism in a patient with a low pretest probability for
venous thromboembolism, so that additional testing can be safely omitted. However, to further improve clinical outcomes, the diagnostic efficiency of combining
D-dimer testing with other markers covering different pathophysiological aspects of
thrombosis such as continuous and progressive
thrombin generation (e.g., activated
protein C-
protein C inhibitor complex) or neutrophil activation (i.e.,
myeloperoxidase) merits further investigation. Proteomic analysis, which would help to characterize the structure and function of each
protein and the complexities of
protein-
protein interactions in physiological and pathological hemostasis, also holds promise for identifying novel markers and developing effective diagnostic protocols in the future.