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| {{SI}}
| | __NOTOC__ |
| {{CMG}} | | {{D-dimer}} |
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| | {{CMG}}; {{AE}} {{Rim}} |
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| ==Overview== | | == [[D-dimer overview|Overview]] == |
| '''D-dimer''' is a [[fibrin degradation product]], a small protein fragment present in the blood after a [[thrombus|blood clot]] is degraded by [[fibrinolysis]].
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| D-dimer concentration may be determined in a [[blood test|tested]] 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 aetiologies. Its main use, therefore, is to exclude thromboembolic disease where the probability is low. | | == [[D-dimer historical perspective|Historical Perspective]] == |
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| ==Indications== | | == [[D-dimer physiology|Physiology]] == |
| D-dimer testing is of clinical use when there is a suspicion of [[deep venous thrombosis]] (DVT) or [[pulmonary embolism]] (PE). In patients suspected of [[disseminated intravascular coagulation]] (DIC), D-dimers may aid in the diagnosis. | |
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| 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).
| | == Clinical Correlation== |
| * 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.
| | [[High D-dimer causes|Causes of High D-dimer]] | [[D-dimer diagnostic role in thromboembolism|Diagnostic Role in Thromboembolism]] | [[D-dimer prognostic role in mortality|Prognostic Role in Mortality]] | [[D-dimer prognostic role in thromboembolism occurrence|Prognostic Role in Thromboembolism Occurrence]] | [[D-dimer prognostic role in thromboembolism recurrence|Prognostic Role in Thromboembolism Recurrence]] | [[D-dimer prognostic role in non thromboembolism conditions|Prognostic Role in Non-Thromboembolism]] |
| * For a moderate or low score, or pretest probability:<ref name="pmid14507948">{{cite journal |author=Wells PS, Anderson DR, Rodger M, ''et al'' |title=Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis |journal=N. Engl. J. Med. |volume=349 |issue=13 |pages=1227–35 |year=2003 |pmid=14507948 |doi=10.1056/NEJMoa023153|url=http://content.nejm.org/cgi/content/full/349/13/1227}}</ref>
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| ** 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 your 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%
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| ** If the D-dimer reads high, then further testing ([[medical ultrasonography|ultrasound]] of the leg veins or lung [[scintigraphy]] or [[CTPA|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.
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| 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.<ref>{{cite journal |last=Rathbun |first=SW |coauthors=TL Whitsett, SK Vesely, GE Raskob |year=2004 |title=Clinical utility of D-dimer in patients with suspected pulmonary embolism and nondiagnostic lung scans or negative CT findings |journal=Chest |issue=125 |pages=851 |accessdate= 2007-11-17}}</ref>
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| ==Reference range==
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| Most sampling kits have 0-300 [[1 E-12 kg|ng]]/[[millilitre|ml]] as normal range. Values exceeding 250, 300 or 500 ng/ml (different for various kits) are considered positive.
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| ==Types of assays==
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| * [[ELISA]] (e.g. Vidas)
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| * Latex turbidimetric assay (automated immunoassay, e.g. Roche Tina-quant, MDA D-dimer)
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| * Enhanced microlatex
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| * Latex-enhanced photometric
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| * Whole Blood Agglutination (e.g. SimpliRED)
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| * Rapid Lateral Flow (e.g. Clearview Simplify)
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| ==Principles==
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| [[Fibrin degradation product]]s (FDPs) are formed whenever [[fibrin]] is [[proteolysis|broken down]] by [[enzyme]]s (e.g. [[plasminogen|plasmin]]). Determining FDPs is not considered useful, as this does not indicate whether the fibrin is part of a blood clot (or being generated as part of [[inflammation]]).
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| D-dimers are unique in that they are the breakdown products of a fibrin mesh that has been stabilized by [[Factor XIII]]. This factor crosslinks the E-element to ''two'' D-elements. This is the final step in the generation of a thrombus. | |
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| [[Plasmin]] is a [[fibrinolysis|fibrinolytic]] enzyme that organizes clots and breaks down the fibrin mesh. It cannot, however, break down the bonds between one E and two D units. The protein fragment thus left over is a D-dimer.
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| D-dimer assays rely on [[monoclonal antibody|monoclonal antibodies]] to bind to this specific protein fragment. The first patented MoAb of the kind was ''D Dimer-3B6/22'', although others have been developed.
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| [[Image:D-dimer.png|left|framed|Principles of D-dimer testing]] | |
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| ==Test Properties==
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| Various kits have a 93-95% sensitivity and about 50% specificity in the diagnosis of thrombotic disease.<ref>Schrecengost JE, LeGallo RD, Boyd JC, Moons KG, Gonias SL, Rose CE Jr, Bruns DE. Comparison of diagnostic accuracies in outpatients and hospitalized patients of D-dimer testing for the evaluation of suspected pulmonary embolism. Clin Chem 2003;49:1483-90. PMID 12928229.</ref>
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| * [[False positive]] readings can be due to various causes: [[liver]] disease, high [[rheumatoid factor]], [[inflammation]], [[cancer|malignancy]], [[Physical trauma|trauma]], [[pregnancy]], recent [[surgery]] as well as advanced age
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| * [[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.
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| * Likelihood ratios are derived from sensitivity and specificity to adjust pretest probability.
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| ==History==
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| D-dimer testing was originally developed in the diagnosis of disseminated intravascular coagulation. In the [[1990s]], they turned out to be useful in diagnosing thromboembolic process. | |
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| ==References==
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| {{reflist|2}}
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| ==External links==
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| * [http://www.d-dimer.co.uk D-dimer reference centre] (site of BBInternational Limited, a manufacturer of D-dimer sampling kits)
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| | ==Cinical Trials== |
| | [[D-dimer landmark trials|Landmark Trials]] |
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| [[Category:Cardiology]] | | [[Category:Cardiology]] |
| [[Category:Pulmonology]] | | [[Category:Pulmonology]] |
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| [[es:Dímero-D]]
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| [[id:D-dimer]]
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| [[nl:D-dimeer]]
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| [[ja:D-ダイマー]]
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| [[pt:Dímeros-D]]
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| {{WH}} | | {{WH}} |
| {{WS}} | | {{WS}} |