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| | {{D-dimer}} |
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| ==Overview==
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| '''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 overview|Overview]] == |
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| ==Historical Perspective== | | == [[D-dimer historical perspective|Historical Perspective]] == |
| 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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| ==Physiology== | | == [[D-dimer physiology|Physiology]] == |
| [[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. | | == Clinical Correlation== |
| | [[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]] |
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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.
| | ==Cinical Trials== |
| | | [[D-dimer landmark trials|Landmark Trials]] |
| [[Image:D-dimer.png|left|framed|Principles of D-dimer testing]]
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| <br clear="left"/>
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| ==D-Dimer Test==
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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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| ===Indications===
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| 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).
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| * 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.
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| * 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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| For patients over age 50 a value of ageX10 may be abnormal.<ref name="pmid23645857">{{cite journal| author=Schouten HJ, Geersing GJ, Koek HL, Zuithoff NP, Janssen KJ, Douma RA et al.| title=Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. | journal=BMJ | year= 2013 | volume= 346 | issue= | pages= f2492 | pmid=23645857 | doi=10.1136/bmj.f2492 | pmc=PMC3643284 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23645857 }} </ref><ref name="pmid22072293">{{cite journal| author=van Es J, Mos I, Douma R, Erkens P, Durian M, Nizet T et al.| title=The combination of four different clinical decision rules and an age-adjusted D-dimer cut-off increases the number of patients in whom acute pulmonary embolism can safely be excluded. | journal=Thromb Haemost | year= 2012 | volume= 107 | issue= 1 | pages= 167-71 | pmid=22072293 | doi=10.1160/TH11-08-0587 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22072293 }} </ref><ref name="pmid20354012">{{cite journal| author=Douma RA, le Gal G, Söhne M, Righini M, Kamphuisen PW, Perrier A et al.| title=Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts. | journal=BMJ | year= 2010 | volume= 340 | issue= | pages= c1475 | pmid=20354012 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20354012 | doi=10.1136/bmj.c1475 }} </ref>
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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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| ==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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| ==References==
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| {{reflist|2}}
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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}} |