Biochemical markers for the diagnosis of venous thromboembolism: the past, present and future

Abstract

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.

Does Limb Preconditioning Reduce Pain After Total Knee Arthroplasty? A Randomized, Double-blind Study

“…Third, muscle tissue oxygenation was measured using a novel noninvasive nearinfrared spectroscopy device at baseline and at 48 hours postoperatively [20]. To test if the use of preconditioning would adversely affect the patients' coagulation status, we measured systemic levels of the procoagulatory markers prothrombin fragments F1/F2, D-dimer, and TAT at the following time points: (1) preoperatively; (2) after tourniquet release; and (3) 3 hours postoperatively [11].…”

“…(2) Can preconditioning decrease local inflammation as evaluated by the extent of postoperative periarticular circumference, levels of cytokines found in the intraarticular fluid, and levels of muscle tissue oxygenation in the operative limb, thus potentially providing a hypothetical mechanism for discrepancies in pain levels found previously? (3) Is preconditioning associated with an increase in systemic levels of coagulation markers (prothrombin fragments F1/F2, D-dimer, and thrombin-antithrombin complex [TAT] [11,17]) between the groups and across various time points? (4) Does preconditioning impact on the length of stay and achievement of physical therapy milestones as found in the previous study?…”

Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

“…27 Therefore, D-dimer and TAT are both proteolytic products of coagulation factors after the activation of coagulation and subsequent fibrinolytic cascades. 26,28 Consequently, elicitation of circulating D-dimer and TAT suggests an induction of coagulation activation or disseminated intravascular coagulation (DIC). 26,28 To investigate role of LT on the induction of DIC, which was reported in B. anthracis-challenged animals, [29][30][31] we analyzed the plasma levels of D-dimer and TAT complex ( Fig.…”

The correlation of D-dimer levels with patient outcomes in acute ischemic cerebrovascular disease complicating coronary heart disease

“…38 The generation of D-dimer occurs in two main steps, the first is for fibrin monomers to be crosslinked by activated factor XIII (FXIIIa), the second is for the crosslinked monomers to then be hydrolyzed by fibrinolytic enzyme hydrolysis. 39 Thus, in general, the elevation of plasma D-dimer levels is a reflection of either secondary hyperfibrinolysis, 40 or the frequent/ continuous process of thrombosis and thrombolysis. 39 That is to say elevated D-dimer levels prompt hyperfunction of coagulation and fibrinolysis.…”