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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 2 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.
Diagnosis of intravascular coagulation and fibrinolysis, also known as disseminated intravascular coagulation, especially when combined with clinical information and other laboratory test data (eg, platelet count, assays of clottable fibrinogen and soluble fibrin monomer complex, and clotting time assays-prothrombin time and activated partial thromboplastin time).(2)
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.(3-6)
D-dimer values < or =250 ng/mL D-dimer units (DDU) (< or =0.50 mcg/mL fibrinogen equivalent units: FEU) are normal. Within the reportable normal range (110-250 ng/mL DDU; 0.22-0.50 mcg/mL FEU), measured values may reflect the activation state of the procoagulant and fibrinolytic systems, but the clinical utility of such quantitation is not established.
A normal D-dimer result (< or =250 ng/mL DDU; < or =0.50 mcg/mL FEU) 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.
-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.
< or =250 ng/mL D-Dimer Units (DDU)
< or =0.5 mcg/mL Fibrinogen Equivalent Units (FEU)
1. Feinstein DI, Marder VJ, Colman RW: Consumptive thrombohemorrhagic disorders. In Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Third edition. Edited by RW Colman, J Hirsh, VJ Marder, et al. Philadelphia, PA, JB Lippincott Co., 2001, pp 1197-1234
2. Levi M, ten Cate H: Disseminated intravascular coagulation. N Engl J Med 1999 August;341(8):586-592
3. Brill-Edward P, Lee A: D-dimer testing in the diagnosis of acute venous thromboembolism. Thromb Haemost 1999 August;82(2):688-694
4. Heit JA, Minor TA, Andrews JC, et al: Determinants of plasma fibrin D-dimer sensitivity for acute pulmonary embolism as defined by pulmonary angiography. Arch Pathol Lab Med 1999 March;123(3):235-240
5. Heit JA, Meyers BJ, Plumhoff EA, et al: Operating characteristics of automated latex immunoassay tests in the diagnosis of angiographically-defined acute pulmonary embolism. Thromb Haemost 2000 June;83(6):970
6. Bates SM, Grand'Maison A, Johnston M, et al: A latex D-dimer reliably excludes venous thromboembolism. Arch Intern Med 2001 February;161(3):447-453