Clinical and Interpretive

The d-dimer is useful in excluding the diagnosis of acute pulmonary embolism or deep vein thrombosis, particularly when results of a sensitive D-dimer assay are combined with clinical information, including pretest disease probability. The d-dimer is useful in diagnosis of disseminated intravascular coagulation; however, it is only useful when combined with clinical information and other laboratory test data. If DIC is a clinical consideration, please order a DIC screen (test code DIC) instead of d-dimer, which also includes pathologist interpretation.

Thrombin, the terminal enzyme of the plasma procoagulant cascade, cleaves fibrinopeptides A and B from fibrinogen, generating fibrin monomer. Fibrin monomer contains D domains on each end of the molecule and a central E domain. Most of the fibrin monomers polymerize to form insoluble fibrin, or the fibrin clot, by repetitive end-to-end alignment of the D domains of two adjacent molecules in lateral contact with the E domain of a third  molecule. The fibrin clot is subsequently stabilized by thrombin-activated factor XIII, which covalently cross-links fibrin monomers by transamidation, including dimerization of the D domains of adjacently polymerized fibrin monomers. The fibrin clot promotes activation of fibrinolysis by catalyzing the activation of plasminogen (by plasminogen activators) to form plasmin enzyme. Plasmin proteolytically degrades cross-linked fibrin, ultimately producing soluble fibrin degradation products of various sizes that include cross-linked fragments containing neoantigenic D-dimer (DD) epitopes. Plasmin also degrades fibrinogen to form fragments X, Y, D, and E. D-dimer immunoassays use monoclonal antibodies to DD neoantigen and mainly detect cross-linked fibrin degradation products, whereas the fibrino(geno)lytic degradation products X, Y, D, and E and their polymers may be derived from fibrinogen or fibrin. Therefore, the blood content of D-dimer indirectly reflects the generation of thrombin and plasmin, roughly indicating the turnover or activation state of the coupled blood procoagulant and fibrinolytic mechanisms.

A normal D-dimer result has a negative predictive value of approximately 95% for the exclusion of acute pulmonary embolism (PE) or deep vein thrombosis when there is low or moderate pretest PE probability.

Increased D-dimer values are abnormal but do not indicate a specific disease state. D-dimer values may be increased as a result of:
-Clinical or subclinical disseminated intravascular coagulation/intravascular coagulation and fibrinolysis
-Other conditions associated with increased activation of the procoagulant and fibrinolytic mechanisms such as recent surgery, active or recent bleeding, hematomas, trauma, or thromboembolism
-Association with pregnancy, liver disease, inflammation, malignancy or hypercoagulable (procoagulant) states

The degree of D-dimer increase does not definitely correlate with the clinical severity of associated disease states.

Lipemia can interfere with this assay, occasionally causing an under-estimation of the D-dimer level. Therefore, results from lipemic specimens should be interpreted with caution.

The presence of rheumatoid factor at a level >50 IU/mL may lead to an over-estimation of the D-dimer level.