D-Dimer

Coagulation activation results in the cleavage of fibrinogen to fibrin monomer.^7,8 The fibrin monomers spontaneously aggregate to fibrin and are cross-linked by factor XIII; this produces a fibrin clot. In response to the coagulation process the fibrinolytic system is activated resulting in the conversion of plasminogen into plasmin, which cleaves fibrin (and fibrinogen) into the fragments D and E. Due to cross-linkage between D-domains in the fibrin clot, the action of plasmin releases fibrin degradation products with cross-linked D-domains. The smallest unit is D-dimer. Detection of D-dimers, which specifies cross-linked fibrin degradation products generated by reactive fibrinolysis, is an indicator of coagulation activity. Fibrin degradation products are not consistently "D-dimer" but are a mixture of fragments and complexes of different molecular weight. The presence of D-dimer confirms that both thrombin and plasmin have been generated since it can only be produced as the result of the plasmin degradation of cross-linked fibrin. The in vivo half-life of D-dimer is approximately eight hours.¹¹

Elevated D-dimer levels are observed in all diseases and conditions with increased coagulation activation, eg, thromboembolic disease, DIC, acute aortic dissection, myocardial infarction, malignant diseases, obstetrical complications, third trimester of pregnancy, surgery, or polytrauma.^12-17 However, in the context of venous thromboembolism, symptoms being present since a certain period of time, eg, longer than a week, may produce normal D-dimer values.¹⁸ For the diagnosis of DIC a scoring system has been suggested, in which elevated D-dimer levels represent the major indicator of DIC.¹² While increased levels of D-dimer are not specific for DVT or PE, low D-dimer levels may be used to rule out these conditions. The negative predictive values for DVT and PE are approaching 100% for the Innovance D-dimer assay employing a cutoff of <0.5 mg/L FEU. The negative predictive value is further enhanced through the use of a clinical probability model along with D-dimer in the decision process.^12-15 Values less than 0.5 mg/L FEU in an individual with a low clinical risk of venous thrombosis can serve as the basis for not performing more expensive diagnostic tests for DVT and PE. Patients with results greater than this cutoff require further diagnostic testing to establish the diagnosis.

D-dimer levels are known to increase with age; eg, median D-dimer levels in apparently healthy men aged 75 to 79 are about twice as high as in men aged 60 to 64.¹⁹ This increase in the basal D-dimer concentration is responsible for the decrease in the specificity of D-dimer measurements for exclusion of VTE in the elderly. Several studies on D-dimer for exclusion of venous thromboembolism (VTE) have been reëvaluated using an age-specific cutoff.^20-23 The aim was to improve the effectiveness of D-dimer testing in ruling out VTE.^20-23 The cutoff provided with the patient result is the manufacturer-determined value for exclusion of VTE; however, it has been determined that D-dimer values increase with age, and this can make VTE exclusion of an older population difficult. To address this, the American College of Physicians, based on best available evidence and recent guidelines, recommends that clinicians use age-adjusted D-dimer thresholds in patients greater than 50 years of age with: (a) a low probability of PE who do not meet all "pulmonary-embolism-rule-out criteria," or (b) in those with intermediate probability of PE.²¹ The formula for an age-adjusted D-dimer cutoff is "age/100." For example, a 60-year-old patient would have an age-adjusted cutoff of 0.6 mg/L FEU, and an 80-year-old patient would have an age-adjusted cutoff of 0.8 mg/L FEU.