D-dimer

D-dimer

D-dimer is a fibrin degradation product (or FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two crosslinked D fragments of the fibrinogen protein.[1]

D-dimer concentration may be determined by a blood test to help diagnose thrombosis. Since its introduction in the 1990s, it has become an important test performed in patients suspected of thrombotic disorders. While a negative result practically rules out thrombosis, a positive result can indicate thrombosis but does not rule out other potential causes. Its main use, therefore, is to exclude thromboembolic disease where the probability is low. In addition, it is used in the diagnosis of the blood disorder disseminated intravascular coagulation.[1]

Contents

Principles

Principles of D-dimer testing

Coagulation, the formation of a blood clot or thrombus, occurs when the proteins of the "coagulation cascade" are activated, either by contact with damaged blood vessel wall (intrinsic pathway) or by activation of factor VII by tissue activating factors. Both pathways lead to the generation of thrombin, an enzyme that turns the soluble blood protein fibrinogen into fibrin, which aggregates into proteofibrils. Another thrombin-generated enzyme, factor XIII, then crosslinks the fibrin proteofibrils at the D fragment site, leading to the formation of an insoluble gel which serves as a scaffold for blood clot formation.[1]

The circulating enzyme plasmin, the main enzyme of fibrinolysis, cleaves the fibrin gel in a number of places. The resultant fragments, "high molecular weight polymers", are digested several times more by plasmin to lead to intermediate and then to small polymers (fibrin degradation products or FDPs). The cross-link between two D fragments remains intact, however, and these are exposed on the surface when the fibrin fragments are sufficiently digested. The typical D-dimer containing fragment contains two D domains and one E domain of the original fibrinogen molecule.[1]

D-dimers are not normally present in human blood plasma, except when the coagulation system has been activated, for instance because of the presence of thrombosis or disseminated intravascular coagulation. The D-dimer assay depends on the binding of a monoclonal antibody to a particular epitope on the D-dimer fragment. Several detection kits are commercially available; all of them rely on a different monoclonal antibody against D-dimer. Of some of these it is known to which area on the D-dimer the antibody binds. The binding of the antibody is then measured quantitatively by one of various laboratory methods.[1]

Indications

D-dimer testing is of clinical use when there is a suspicion of deep venous thrombosis (DVT), pulmonary embolism (PE) or disseminated intravascular coagulation (DIC).[2] It can also rise postoperatively.[2] It is under investigation in the diagnosis of aortic dissection.[3][4]

For DVT and PE, there are various scoring systems that are used to determine the a priori clinical probability of these diseases; the best-known were introduced by Wells et al. (2003).

  • For a very high score, or pretest probability, a D-dimer will make little difference and anticoagulant therapy will be initiated regardless of test results, and additional testing for DVT or pulmonary embolism may be performed.
  • For a moderate or low score, or pretest probability:[5]
    • A negative D-dimer test will virtually rule out thromboembolism: the degree to which the D-dimer reduces the probability of thrombotic disease is dependent on the test properties of the specific test used in the clinical setting: most available D-dimer tests with a negative result will reduce the probability of thromboembolic disease to less than 1% if the pretest probability is less than 15-20%
    • If the D-dimer reads high, then further testing (ultrasound of the leg veins or lung scintigraphy or CT scanning) is required to confirm the presence of thrombus. Anticoagulant therapy may be started at this point or withheld until further tests confirm the diagnosis, depending on the clinical situation.

In some hospitals, they are measured by laboratories after a form is completed showing the probability score and only if the probability score is low or intermediate. This would reduce the need for unnecessary tests in those who are high-probability.[6]

Test properties

Various kits have a 93-95% sensitivity and about 50% specificity in the diagnosis of thrombotic disease.[7]

  • False positive readings can be due to various causes: liver disease, high rheumatoid factor, inflammation, malignancy, trauma, pregnancy, recent surgery as well as advanced age[citation needed]
  • False negative readings can occur if the sample is taken either too early after thrombus formation or if testing is delayed for several days. Additionally, the presence of anti-coagulation can render the test negative because it prevents thrombus extension.
  • Likelihood ratios are derived from sensitivity and specificity to adjust pretest probability.

History

D-dimer was originally described in the 1970s, and found its diagnostic application in the 1990s.[1]

References

  1. ^ a b c d e f Adam SS, Key NS, Greenberg CS (March 2009). "D-dimer antigen: current concepts and future prospects". Blood 113 (13): 2878–2887. doi:10.1182/blood-2008-06-165845. PMID 19008457. http://bloodjournal.hematologylibrary.org/cgi/content/full/113/13/2878. 
  2. ^ a b General Practice Notebook > D-dimer Retrieved September 2011
  3. ^ Suzuki, T.; Distante, A.; Eagle, K. (2010). "Biomarker-assisted diagnosis of acute aortic dissection: How far we have come and what to expect". Current Opinion in Cardiology 25 (6): 541–545. doi:10.1097/HCO.0b013e32833e6e13. PMID 20717014.  edit
  4. ^ Ranasinghe, A. M.; Bonser, R. S. (2010). "Biomarkers in Acute Aortic Dissection and Other Aortic Syndromes". Journal of the American College of Cardiology 56 (19): 1535–1541. doi:10.1016/j.jacc.2010.01.076. PMID 21029872.  edit
  5. ^ Wells PS, Anderson DR, Rodger M et al. (2003). "Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis". N. Engl. J. Med. 349 (13): 1227–1235. doi:10.1056/NEJMoa023153. PMID 14507948. http://content.nejm.org/cgi/content/full/349/13/1227. 
  6. ^ Rathbun, SW; TL Whitsett, SK Vesely, GE Raskob (2004). "Clinical utility of D-dimer in patients with suspected pulmonary embolism and nondiagnostic lung scans or negative CT findings". Chest 125 (3): 851–855. doi:10.1378/chest.125.3.851. PMC 1215466. PMID 15006941. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1215466. 
  7. ^ Schrecengost JE, LeGallo RD, Boyd JC et al. (September 2003). "Comparison of diagnostic accuracies in outpatients and hospitalized patients of D-dimer testing for the evaluation of suspected pulmonary embolism". Clinical Chemistry 49 (9): 1483–1490. doi:10.1373/49.9.1483. PMID 12928229. 

Wikimedia Foundation. 2010.

Игры ⚽ Поможем решить контрольную работу

Look at other dictionaries:

  • dîmer — ● dîmer verbe intransitif Percevoir la dîme ecclésiastique. ● dîmer (synonymes) verbe intransitif Percevoir la dîme ecclésiastique. Synonymes : taxer ⇒DÎMER, verbe. Vieux A. Emploi intrans. [Gén. suivi d un compl. circ. de lieu] Lever la dîme.… …   Encyclopédie Universelle

  • Dimer acid — Dimer acids, or dimerized fatty acids, are dicarboxylic acids prepared by dimerizing unsaturated fatty acids obtained from tall oil, usually on clay catalysts. The CAS number of the material is [61788 89 4]. Dimer acids are used primarily for… …   Wikipedia

  • Dimer — may refer to: Dimer (chemistry), a chemical structure formed from two sub units Dimer model, an item in statistical mechanics Protein dimer, a protein quaternary structure Julius Dimer (1871–1945), a German chess master Dimerous refer to plants… …   Wikipedia

  • dimer — DIMÉR, dimeri, s.m. Compus chimic rezultat din combinarea a două molecule din aceeaşi specie de substanţe. – Din fr. dimère. Trimis de LauraGellner, 13.07.2004. Sursa: DEX 98  DIMÉR s. (fiz., chim.) moleculă dublă. Trimis de siveco, 05.08.2004.… …   Dicționar Român

  • dîmer — DÎMER. v. n. Avoir droit de lever la dîme en un lieu. Cet Abbé dîme dans tous ces Villages. f♛/b] Il se dit aussi en parlant De celui qui, actuellement, lève la dîme. On n a pas dîmé en ce champ là. Il est allé dîmer au pressoir. [b]Dîmé, ée.… …   Dictionnaire de l'Académie Française 1798

  • dimer — [dī′mər] n. [ DI 1 + (POLY)MER] a compound formed by the combination of two identical molecules or monomers dimeric [dī′mer′ik] adj …   English World dictionary

  • Dimer (chemistry) — For other uses, see Dimer (disambiguation). Dimers of carboxylic acids are often found in vapour phase. A dimer is a chemical entity consisting of two structurally similar subunits called monomers joined by bonds that can be either strong or weak …   Wikipedia

  • dîmer — (di mé) v. n. 1°   Lever la dîme. Dîmer dans un champ, sur un vignoble. L abbé dîmait dans tous ses villages. 2°   Fig. Faire un prélèvement. •   Nous laissant dîmer sur un bien Qui ne vous coûte presque rien, LA FONT. Cord..    Activement.… …   Dictionnaire de la Langue Française d'Émile Littré

  • Dimer — Ein Dimer ist ein Molekül oder ein Molekülverbund, der aus zwei oft identischen Untereinheiten, den Monomeren, besteht. In Bezug auf die Größe, die Molekülmasse und die Komplexität ist das Dimer das einfachste Oligomer bzw. Polymer. Den Vorgang… …   Deutsch Wikipedia

  • DÎMER — v. n. Lever la dîme. Dîmer dans un champ. Dîmer sur un quartier de vigne. Dîmer au pressoir.   Il signifie aussi, Avoir droit de lever la dîme en un lieu. Cet évêque, ce seigneur dîmait sur toutes les terres à une lieue à la ronde. L abbé dîmait… …   Dictionnaire de l'Academie Francaise, 7eme edition (1835)

  • dimer — oligomer o*lig o*mer, n. (Chem.) A molecule composed of a small number of linked monomer units; a short polymer; compounds called oligomers have less than one hundred monomer units and usually less than thirty. Oligomers of increasing length are… …   The Collaborative International Dictionary of English

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”