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D Dimer and its Clinical significance

Date : 13 Jul, 2018

Fibrin Degradation Products (FDP)

Fibrinogen contains two identical subunits that consist of three polypeptide chains: α, β, and γ. During coagulation process, fibrinogen is first converted into fibrin monomer by thrombin, and the polymerization of these monomers result in fibrin clot formation. In fibrinolysis, the fibrin clots are dissolved by plasmin, and Fibrin Degradation Products (FDP) of different molecular weights are released into the bloodstream (Fig. 1).

D-dimer is a remarkable subtype of FDPs. D-Dimers are the derivatives of cross-linked fibrin and its concentration increases due to thrombolysis process. During fibrin clot formation, factor XIII creates little cross-links between the fibrin molecules. When the fibrin starts degrading, some of the resulting fragments contain these little cross-links. These little fragments contain one “E” fibrin subunit and two “D” subunits; called as D-dimers. D-dimer (MW 180 kDa) is the final product of “fibrin” degradation. It consists of α, β and γ chains of fibrinogen cross linked by disulfide bonds.

D-dimer testing can be useful in analyzing thrombin and plasmin generation process i.e., generation of thrombin resulting in the lysis of cross-linked fibrin clot. Hence, its clinical significance is very critical in diseases like Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), Disseminated Intravascular Coagulation (DIC), trauma, liver disease, malignancy, and inflammation. Normally, D-dimers are absent in the human plasma, but an elevated level of D-dimer is observed in the above mentioned diseases.

Process of Fibrinolysis
Fig. 1 Process of Fibrinolysis (Source: http://www.what-when-how.com)

D-dimer tests have been used in clinical practices since 1970s and there are many challenges in the quantitative determination of D-dimer in plasma samples. As all FDPs contains the same “D-dimer antigen epitope”, antibodies specific to D-dimer also recognize a wide spectrum of FDPs of different sizes along with D-dimer itself. The monoclonal antibodies against D-dimer are widely used in the testing for D-dimer detection where latex microparticles coated with monoclonal antibodies specific for D-dimer epitopes are used. 

Currently, the measurement of FDPs has largely been replaced by a variety of more-sensitive commercial D-dimer testing platforms and the results are expressed in Fibrinogen Equivalent Unit (FEU). 

Erba D Dimer R kit is an immunoturbidometric assay intended for the D-dimer detection. D Dimer is present in the sample agglutinates, with the monoclonal antibodies bound to specific latex particles. 

The immunocomplex formed, is measured photo-optically at 800 nm. The reagents are ready to use and has a stability of 4 weeks.

Reference:

  1. Fibrinogen degradation products and d-dimers in patients with breast carcinoma; Malik Zeb Khan, Muhammad Shoaib Khan, Fazle Raziq, Aziz Marjan Khattak; Gomal Journal of Medical Sciences Jan–June, 2007, Vol. 5, No. 1

  2. Widely used types and Clinical applications of D-Dimer assay; Roger S. Riley, Andrea R. Gilbert, Justin B. Dalton, Sheela Pai, Richard A. McPherson; Lab Medicine 2016; 1–13