D-dimer immunoassay is useful in the diagnosis of intravascular

coagulation and fibrinolysis (ICF), also known as disseminated

intravascular coagulation (DIC), 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.)

Studies have also demonstrated the negative predictive value of

normal D-dimer assay results in excluding the diagnosis of acute

pulmonary embolism (PE) or deep vein thrombosis(DVT), particularly

when results of a sensitive D-dimer assay are combined with clinical

information, including pretest disease probability.

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 3rd  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.

Plasma D-dimer levels may be increased in individuals with clinical

or subclinical disseminated intravascular coagulation (DIC)/

intravascular coagulation and fibrinolysis (ICF), and in other conditions

associated with increased activation of the procoagulant and

fibrinolytic mechanisms such as with active or recent bleeding,

hematomas, trauma, surgical operation, or thromboembolism. Increased

D-dimer values can also occur in association with pregnancy, liver

disease, malignancy, inflammation, or chronic hypercoagulable

states.

< or = 250 ng/mL

D-dimer values < or = 250 ng/mL are normal. Within the reportable

reference range (110-250 ng/mL), 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) has a negative predictive

value of approximately 95% for the exclusion of acute PE when there

is low or moderate pretest PE probability. The negative predictive

value is probably somewhat less (approximately 90%) for excluding

low or moderate probability acute deep vein thrombosis (DVT).

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 DIC/ICF, recent surgery, bleeding, trauma, or

thromboembolism; or in 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 the D-dimer assay. Therefore, results from

severely lipemic specimens will be released with the comment

"D-dimer level may be under-estimated due to possible lipemic

Interference."

The presence of rheumatoid factor at a level >50 IU/mL may lead to

an over-estimation of the D-dimer level.

1.   Francis CW, Marder VJ:  Physiologic regulation and pathologic

      disorders of fibrinolysis. In Hemostasis and Thrombosis:

      Basic Principles and Clinical Practice. 3rd edition. Edited by

      RW Colman, J Hirsh, VJ Marder, EJ Salzman. Philadelphia,

      JB Lippincott Company. 1994, pp 1076-1103

2.   Levi M,Ten Cate H:  Disseminated intravascular coagulation.

      N Engl J Med 1999;341:586-592,

3.   Brill-Edwards P, Lee A:  D-dimer testing in the diagnosis of acute

      venous thromboembolism. Thromb Haemost 1999;82:688-694

4.   Heit JA, Meyers BJ, Plumhoff EA, et al:  Operating characteristics

      of automated plasma fibrin D-dimer assays in the diagnosis

      of angiographically - defined acute pulmonary embolism.

      Thromb Haemost 2000;83:970

5.   Bates SM, Grand'Maison A, Johnston M, et al:  A latex D-dimer reliably

      excludes venous thromboembolism. Thromb Haemost 1999;82:258