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| __NOTOC__ | | __NOTOC__ |
| {{SI}} | | {{D-dimer}} |
| '''Editor(s)-In-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com], {{ATI}}; {{AE}} {{CZ}}
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| ==Overview==
| | {{CMG}}; {{AE}} {{Rim}} |
| [[D-dimer]] is a [[fibrin degradation product]]. D-dimer levels are elevated in the plasma after the acute formation of a blood clot. The majority of patients with pulmonary embolism have some degree of endogenous [[fibrinolysis]] with an elevation in [[D-dimer]] levels, therefore there is a high [[negative predictive value]] in ruling out a pulmonary embolism when D-dimer levels are low. However a wide range of diseases are associated with mild degree of [[fibrinolysis]] which elevate [[D-dimer]] levels and contribute towards a reduced [[specificity]] and a poor [[positive predictive value]] of a high D-dimer level. This means that it is more likely that one can rule out a PE with a low D-dimer level, but cannot necessarily confirm the diagnosis of a PE based on a high D-dimer level. Other disease states that can also have a high d-dimer level include [[pneumonia]], [[Congestive heart failure|congestive heart failure (CHF)]], [[Myocardial infarction|myocardial infarction (MI)]] and [[malignancy]]. [[False-negative]] values may occur in patients with prolonged symptoms of [[venous thromboembolism]] (≥14 days), patients on therapeutic [[heparin|heparin therapy]], and patients with suspected [[deep venous thrombosis]] on oral anticoagulation, as these patients have will have low D-dimer levels in the presence of a PE.<ref name="pmid19712840">{{cite journal| author=Bruinstroop E, van de Ree MA, Huisman MV| title=The use of D-dimer in specific clinical conditions: a narrative review. | journal=Eur J Intern Med | year= 2009 | volume= 20 | issue= 5 | pages= 441-6 | pmid=19712840 | doi=10.1016/j.ejim.2008.12.004 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19712840 }} </ref><ref name="pmid20592294">{{cite journal| author=Agnelli G, Becattini C| title=Acute pulmonary embolism. | journal=N Engl J Med | year= 2010 | volume= 363 | issue= 3 | pages= 266-74 | pmid=20592294 | doi=10.1056/NEJMra0907731 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20592294 }} </ref>
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| ==Historical Perspective==
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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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| ==Physiology== | | == [[D-dimer overview|Overview]] == |
| [[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. | | == [[D-dimer historical perspective|Historical Perspective]] == |
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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. | | == [[D-dimer physiology|Physiology]] == |
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| [[Image:D-dimer.png|left|framed|Principles of D-dimer testing]] | | == Clinical Correlation== |
| <br clear="left"/>
| | [[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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| ==D-Dimer Test== | | ==Cinical Trials== |
| | [[D-dimer landmark trials|Landmark Trials]] |
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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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| == D-dimer and Thromboembolism==
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| === Abnormal Levels ===
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| [[D-dimer|Plasma D-dimer]] levels > 500 ng/mL are abnormal.<ref name="pmid15096330">{{cite journal |author=Stein PD, Hull RD, Patel KC, Olson RE, Ghali WA, Brant R, Biel RK, Bharadia V, Kalra NK |title=D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review |journal=[[Annals of Internal Medicine]] |volume=140 |issue=8 |pages=589–602 |year=2004 |month=April |pmid=15096330 |doi= |url= |accessdate=2012-05-07}}</ref>
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| === Sensitivity and Specificity ===
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| ====Sensitivity<ref name="pmid15096330">{{cite journal |author=Stein PD, Hull RD, Patel KC, Olson RE, Ghali WA, Brant R, Biel RK, Bharadia V, Kalra NK |title=D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review |journal=[[Annals of Internal Medicine]] |volume=140 |issue=8 |pages=589–602 |year=2004 |month=April |pmid=15096330 |doi= |url= |accessdate=2012-05-07}}</ref>====
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| [[ELISA]] ''(p=0.020)'', [[ELISA|quantitative rapid ELISA]] ''(p=0.016)'' and [[ELISA|semi-quantitative ELISA]] ''(p=0.047)'' are shown to be statistically superior to [[agglutination|whole-blood agglutination]].
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| ====Specificity<ref name="pmid15096330">{{cite journal |author=Stein PD, Hull RD, Patel KC, Olson RE, Ghali WA, Brant R, Biel RK, Bharadia V, Kalra NK |title=D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review |journal=[[Annals of Internal Medicine]] |volume=140 |issue=8 |pages=589–602 |year=2004 |month=April |pmid=15096330 |doi= |url= |accessdate=2012-05-07}}</ref>====
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| [[ELISA|Qualitative rapid ELISA]] has shown to be statistically superior to [[ELISA]] ''(p=0.004)'', [[ELISA|quantitative rapid ELISA]] ''(p=0.002)'', [[ELISA|semi-quantitative rapid ELISA]] ''(p=0.001)'', [[latex agglutination test|quantitative]] ''(p=0.005)'' and [[latex agglutination test|semi-quantitative]] latex agglutination assays ''(p=0.019)''.
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| {| border="1"
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| ! Method !! Sensitivity (95% CI) !! Specificity (95% CI) !! Positive Likelihood Ratio (95% CI) !! Negative Likelihood Ratio (95% CI) !! Time to obtain Results
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| | [[ELISA|Enzyme-linked immunosorbent assay (ELISA)]]
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| | align= "center" | 0.95 (0.85 to 1.00)
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| | align= "center" | NS
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| | align= "center" | NS
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| | align= "center" | 0.13 (0.03 to 0.58)
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| | align= "center" | ≥ 8 hours
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| |-
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| | [[ELISA|Quantitative rapid ELISA]]
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| | align= "center" | 0.95 (0.83 to 1.00)
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| | align= "center" | NS
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| | align= "center" | NS
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| | align= "center" | 0.13 (0.02 to 0.84)
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| | align= "center" | 30 mins
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| |-
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| | [[ELISA|Semi-Quantitative rapid ELISA]]
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| | align= "center" | 0.93 (0.79 to 1.00)
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| | align= "center" | NS
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| | align= "center" | NS
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| | align= "center" | 0.20 (0.04 to 0.96)
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| | align= "center" | 10 mins
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| |-
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| | [[ELISA|Qualitative rapid ELISA]]
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| | align= "center" | NS
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| | align= "center" | 0.68 (0.50 to 0.87)
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| | align= "center" | NS
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| | align= "center" | 0.11 (0.01 to 0.93)
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| | align= "center" | 10 mins
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| |-
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| | [[Latex agglutination test|Quantitative Latex Agglutination]]
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| | align= "center" | NS
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| | align= "center" | NS
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| | align= "center" | NS
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| | align= "center" | NS
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| | align= "center" | 10-15 mins
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| |-
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| | [[Latex agglutination test|Semi-quantitative Latex Agglutination]]
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| | align= "center" | NS
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| | align= "center" | NS
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| | align= "center" | NS
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| | align= "center" | 0.17 (0.04 to 0.78)
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| | align= "center" | 5 mins
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| |-
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| | [[Latex agglutination test|Whole-Blood Agglutination]]
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| | align= "center" | NS
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| | align= "center" | 0.74 (0.60 to 0.88)
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| | align= "center" | NS
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| | align= "center" | NS
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| | align= "center" | 2 mins
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| |}
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| === Hemodynamically Stable Patients ===
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| ====Incidence of Thromboembolic Events in Hemodynamically Stable Patients====
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| {| border="1"
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| ! Condition !! Incidence of thromboembolic event (%)
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| | Patients not receiving anticoagulation with negative CT findings.
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| | 1.5%<ref name="pmid15858185">{{cite journal| author=Perrier A, Roy PM, Sanchez O, Le Gal G, Meyer G, Gourdier AL et al.|title=Multidetector-row computed tomography in suspected pulmonary embolism. | journal=N Engl J Med | year= 2005 | volume= 352|issue= 17 | pages= 1760-8 | pmid=15858185 | doi=10.1056/NEJMoa042905 | pmc=|url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15858185}} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16118905Review in: J Fam Pract. 2005 Aug;54(8):653, 657] </ref><ref name="pmid16403929">{{cite journal| author=van Belle A, Büller HR, Huisman MV, Huisman PM, Kaasjager K, Kamphuisen PW et al.|title=Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. | journal=JAMA | year= 2006 | volume= 295 |issue= 2 | pages= 172-9 | pmid=16403929 | doi=10.1001/jama.295.2.172| pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16403929 }} </ref>
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| | Patients with a high d-dimer level
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| | 1.5%
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| | Patients with a normal d-dimer level
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| | 0.5%<ref name="pmid15858185">{{cite journal| author=Perrier A, Roy PM, Sanchez O, Le Gal G, Meyer G, Gourdier AL et al.|title=Multidetector-row computed tomography in suspected pulmonary embolism. | journal=N Engl J Med | year= 2005 | volume= 352|issue= 17 | pages= 1760-8 | pmid=15858185 | doi=10.1056/NEJMoa042905 | pmc=|url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15858185}} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16118905Review in: J Fam Pract. 2005 Aug;54(8):653, 657] </ref>
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| |}
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| *[[Pulmonary embolism CT#Multi-Detector CT|Multidetector CT]] is indicated in hemodynamically stable patients with a high clinical probability of PE and/or patients with elevated plasma [[d-dimer]] levels secondary to the lack of specificity.<ref name="pmid16403929">{{cite journal| author=van Belle A, Büller HR, Huisman MV, Huisman PM, Kaasjager K, Kamphuisen PW et al.| title=Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. | journal=JAMA | year= 2006 | volume= 295 | issue= 2 | pages= 172-9 | pmid=16403929 | doi=10.1001/jama.295.2.172 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16403929 }} </ref><ref name="pmid19620439">{{cite journal| author=Gupta RT, Kakarla RK, Kirshenbaum KJ, Tapson VF| title=D-dimers and efficacy of clinical risk estimation algorithms: sensitivity in evaluation of acute pulmonary embolism. |journal=AJR Am J Roentgenol | year= 2009 | volume= 193 | issue= 2 | pages= 425-30 | pmid=19620439 |doi=10.2214/AJR.08.2186 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19620439 }} </ref>
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| *In patients with low-to-moderate suspicion of PE, a normal [[D-dimer]] level is considered sufficient to exclude the possibility of pulmonary embolism.<ref name="pmid8165626">{{cite journal |author=Bounameaux H, de Moerloose P, Perrier A, Reber G|title=Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview |journal=Thromb. Haemost.|volume=71 |issue=1 |pages=1-6 |year=1994 |pmid=8165626 |doi=}}</ref>
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| === Flowchart Summarizing the Role of D-dimer in the Diagnosis of PE ===
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| {{familytree/start |summary=Use of D-Dimer.}}
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| {{familytree | | | | GMa | GMa=Patients with suspection of [[Pulmonary embolism]]}}
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| {{familytree | |,|-|-|^|-|-|-|.| | | }}
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| {{familytree |JOE| | | | |SIS| | | JOE=Clinically Low or Moderate|SIS=Clinically High}}
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| {{familytree |,|^|-|.| | | | |!| }}
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| {{familytree |!| | |!| | | | |!| }}
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| {{familytree |!| | |ME| | |!|ME=D-Dimer Positive}}
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| {{familytree |!| | | |!| | | |!| }}
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| {{familytree |MOM| |!| | | |!| |MOM=D-Dimer Negative|}}
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| {{familytree | |!| | |!| | | |!| }}
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| {{familytree |GPa| |ME| |SIS|GPa=No treatment|ME=Further Tests|SIS=Further Tests}}
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| {{familytree/end}}
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| A new D-Dimer (DDMR) analyzer has shown to be more accurate in excluding patients with a low clinical pre-test probability.<ref name="pmid22245223">{{cite journal| author=Gosselin RC, Wu JR, Kottke-Marchant K, Peetz D, Christie DJ, Muth H et al.| title=Evaluation of the Stratus® CS Acute Care™ D-dimer assay (DDMR) using the Stratus® CS STAT Fluorometric Analyzer: A prospective multisite study for exclusion of pulmonary embolism and deep vein thrombosis. | journal=Thromb Res | year= 2012 | volume= | issue= | pages= | pmid=22245223 | doi=10.1016/j.thromres.2011.12.015 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22245223 }} </ref>
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| ==Prognostic Role of D-dimer==
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| ===Mortality and Thromboembolism===
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| * Several studies have investigated the role of D-dimer as a prognostic marker for patients diagnosed with [[pulmonary embolism]]. In fact, according to several studies D dimer level is suggested to have a prognostic role as higher levels of D-dimer are associated with a higher mortality risk.<ref name="pmid22648488">{{cite journal| author=Sanchez O, Planquette B, Roux A, Gosset-Woimant M, Meyer G| title=Triaging in pulmonary embolism. | journal=Semin Respir Crit Care Med | year= 2012 | volume= 33 | issue= 2 | pages= 156-62 | pmid=22648488 | doi=10.1055/s-0032-1311794 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22648488 }} </ref>
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| * Measurement of the level of D-dimer was done on 366 patients presenting to the emergency department. Follow up on these patients revealed a higher mortality risk among patients having a D-dimer level higher than 5500 mg/L. In fact, the overall mortality increased from 1.1% to 9% among patients with D-dimer levels less than 1500mg/L and greater than 5500 mg/L respectively. The [[sensitivity]] and [[specificity]] of D-dimer in predicting mortality were 95% and 26% respectively, while the [[PPV]] and [[NPV]] were 7 % and 99% respectively.<ref name="pmid17003925">{{cite journal| author=Aujesky D, Roy PM, Guy M, Cornuz J, Sanchez O, Perrier A| title=Prognostic value of D-dimer in patients with pulmonary embolism. | journal=Thromb Haemost | year= 2006 | volume= 96 | issue= 4 | pages= 478-82 | pmid=17003925 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17003925 }} </ref>
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| * Another study supported the same association of high D-dimer levels and increased mortality risk and suggested that the best cut-off level of d-dimer to predict mortality is more than 3000 ng/mL (OR= 7.29, CI=95%). In addition to their association with higher mortality risk, elevated levels of D-dimer are associated with centrally located pulmonary embolism.<ref name="pmid18028485">{{cite journal| author=Klok FA, Djurabi RK, Nijkeuter M, Eikenboom HC, Leebeek FW, Kramer MH et al.| title=High D-dimer level is associated with increased 15-d and 3 months mortality through a more central localization of pulmonary emboli and serious comorbidity. | journal=Br J Haematol | year= 2008 | volume= 140 | issue= 2 | pages= 218-22 | pmid=18028485 | doi=10.1111/j.1365-2141.2007.06888.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18028485 }} </ref>
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| * Data results from RIETE registry also supports the association between high levels of D-dimer and fatality from pulmonary embolism (OR=1.8, CI=95%) as well as with higher risk of major bleeding.<ref name="pmid19691481">{{cite journal| author=Lobo JL, Zorrilla V, Aizpuru F, Grau E, Jiménez D, Palareti G et al.| title=D-dimer levels and 15-day outcome in acute pulmonary embolism. Findings from the RIETE Registry. | journal=J Thromb Haemost | year= 2009 | volume= 7 | issue= 11 | pages= 1795-801 | pmid=19691481 | doi=10.1111/j.1538-7836.2009.03576.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19691481 }} </ref>
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| * The prognostic role of D-dimer in hemodynamically stable patients does not have a solid ground. In fact, mixed results are present regarding the association between D-dimer and mortality. According to a study conducted on 292 stable patients with [[PE]], high levels of D-dimer more than 5000 ng/mL were not associated with a higher mortality.<ref name="pmid21288930">{{cite journal| author=Stein PD, Janjua M, Matta F, Alrifai A, Jaweesh F, Chughtai HL| title=Prognostic value of D-dimer in stable patients with pulmonary embolism. | journal=Clin Appl Thromb Hemost | year= 2011 | volume= 17 | issue= 6 | pages= E183-5 | pmid=21288930 | doi=10.1177/1076029610395129 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21288930 }} </ref>
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| ===Recurrence of Thromboembolism===
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| * D-dimer seems to have a good prognostic role in predicting recurrence of thromboembolism. According to PROLONG study, normal levels of D-dimers 1 month following discontinuation of [[anticoagulation]] were associated with a decreased level of thromboembolism recurrences.<ref name="pmid17065639">{{cite journal| author=Palareti G, Cosmi B, Legnani C, Tosetto A, Brusi C, Iorio A et al.| title=D-dimer testing to determine the duration of anticoagulation therapy. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 17 | pages= 1780-9 | pmid=17065639 | doi=10.1056/NEJMoa054444 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17065639 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17335152 Review in: ACP J Club. 2007 Mar-Apr;146(2):29] [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17400637 Review in: Evid Based Med. 2007 Apr;12(2):45] </ref>
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| * PROLONG II study investidated the association between the levels of D-dimers more than one month after [[anticoagulation]] suspension for unprovoked venous [[thromboembolism]]. The results of this study showed that patients who have high levels of D-dimers at 3 months after [[anticoagulation]] suspension have higher thromboembolism recurrences risks than patients who have normal levels of D-dimers. Hence, these studies suggest that the measurement of D-dimer levels at several months intervals following anticoagulation suspension in patient suffering from a first episode of VTE might be beneficial in triaging patients and targeting their therapies.<ref name="pmid21288930">{{cite journal| author=Stein PD, Janjua M, Matta F, Alrifai A, Jaweesh F, Chughtai HL| title=Prognostic value of D-dimer in stable patients with pulmonary embolism. | journal=Clin Appl Thromb Hemost | year= 2011 | volume= 17 | issue= 6 | pages= E183-5 | pmid=21288930 | doi=10.1177/1076029610395129 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21288930 }} </ref>
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| ===Sepsis and Mortality===
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| * Higher D-dimer levels were correlated with high risk of 28 day mortality such as the odds ratio are 2.07 (CI=95%) and 3.03 (CI=95%) in patients having a D-dimer level >1180 and >2409 respectively.<ref name="pmid22795996">{{cite journal| author=Rodelo JR, De la Rosa G, Valencia ML, Ospina S, Arango CM, Gómez CI et al.| title=D-dimer is a significant prognostic factor in patients with suspected infection and sepsis. | journal=Am J Emerg Med | year= 2012 | volume= 30 | issue= 9 | pages= 1991-9 | pmid=22795996 | doi=10.1016/j.ajem.2012.04.033 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22795996 }} </ref>
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| ==D-Dimer and Non Thromboembolism Conditions==
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| ===Age===
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| D-dimer levels physiologically increase with age, making the usefulness of D-dimer among the elderly less significant. The exact mechanism of D-dimer increase with age is poorly understood. It is thought to be related to the expected increase in patient co-morbidities and thrombotic events that occur with age, and that also happen to elevate D-dimer levels. The use of D-dimer in elderly nonetheless remains helpful in diagnosing VTE in low and intermediate risk patients. Age-adjusted D-dimer levels are thought to be useful, especially for the elderly. However, specific age-adjusted values have not been released yet.<ref name="pmid22046531">{{cite journal| author=Der Sahakian G, Claessens YE, Allo JC, Kansao J, Kierzek G, Pourriat JL| title=Accuracy of D-Dimers to Rule Out Venous Thromboembolism Events across Age Categories. | journal=Emerg Med Int | year= 2010 | volume= 2010 | issue= | pages= 185453 | pmid=22046531 | doi=10.1155/2010/185453 | pmc=PMC3195346 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22046531 }} </ref>
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| ===Aortic Dissection===
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| Elevated levels of D-dimer lab test has been used to rapidly rule out emergencies such as acute [[aortic dissection]] (AAD). More than 15 studies that enrolled more than 400 patients have evaluated the use of D-dimer in AAD. With the absence of specific biomarkers, the clinical diagnosis of AAD remains a challenge for clinicians based on clinical suspicion alone. A meta analysis for D-dimer testing in AAD revealed that D-dimer has 97% sensitivity and 59% specificity in diagnosis of AAD. The diagnostic cut-off D-dimer value for patients with AAD ranges between 0.1 and 0.9 µg/mL., with sensitivities ranging between 100% and 86% respectively. Using D-dimer cut-off value similar to that for [[PE]] at a level of 0.5 µg/mL is considered an appropriate level that has a negative predictive value that approximately reaches 100%.<ref name="pmid17986466">{{cite journal| author=Sodeck G, Domanovits H, Schillinger M, Ehrlich MP, Endler G, Herkner H et al.| title=D-dimer in ruling out acute aortic dissection: a systematic review and prospective cohort study. | journal=Eur Heart J | year= 2007 | volume= 28 | issue= 24 | pages= 3067-75 | pmid=17986466 | doi=10.1093/eurheartj/ehm484 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17986466 }} </ref>
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| ===Renal Disease===
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| D-dimer levels is correlated with [[nephrotic syndrome]] and other renal diseases. While some postulate that D-dimer elevation is associated with renal clearance,<ref name="pmid15010654">{{cite journal| author=Shlipak MG, Fried LF, Stehman-Breen C, Siscovick D, Newman AB| title=Chronic renal insufficiency and cardiovascular events in the elderly: findings from the Cardiovascular Health Study. | journal=Am J Geriatr Cardiol | year= 2004 | volume= 13 | issue= 2 | pages= 81-90 | pmid=15010654 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15010654 }} </ref> data is conflicting as to whether D-dimer elevation may be less likely correlated with renal clearance as much as it is associated with [[proteinuria]].<ref name="pmid23221061">{{cite journal| author=Sexton DJ, Clarkson MR, Mazur MJ, Plant WD, Eustace JA| title=Serum D-dimer concentrations in nephrotic syndrome track with albuminuria, not estimated glomerular filtration rate. | journal=Am J Nephrol | year= 2012 | volume= 36 | issue= 6 | pages= 554-60 | pmid=23221061 | doi=10.1159/000345475 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23221061 }} </ref> Nevertheless, the increase of hemostatic markers, such as D-dimer in renal disease, are considered risk factors for [[VTE]] in patients with renal disease.<ref name="pmid21269477">{{cite journal| author=Dubin R, Cushman M, Folsom AR, Fried LF, Palmas W, Peralta CA et al.| title=Kidney function and multiple hemostatic markers: cross sectional associations in the multi-ethnic study of atherosclerosis. | journal=BMC Nephrol | year= 2011 | volume= 12 | issue= | pages= 3 | pmid=21269477 | doi=10.1186/1471-2369-12-3 | pmc=PMC3037849 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21269477 }} </ref>
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| [[Nephrotic syndrome]] is considered a hypercoagulable state that is notoriously associated with [[DVT]] and [[PE]]. Among 100 patients with proteinuria, 53% had elevated D-dimer levels. When proteinuria was more than 1g/24 hours, elevation of D-dimer levels was seen in 69% of patients with proteinuria. D-dimer is believed to be related to the heavy proteinuria in nephrotic syndrome and subsequent hepatic synthesis of [[fibrinogen]], where strong association between D-dimer elevation and hypoalbuminemia is found. It is also suggested that elevated serum fibrinopeptide A, thrombin-antithrombin III complex, along with products of [[thrombin]] and [[prothrombin]], and the state of activated hemostasis in nephrotic syndrome causes the elevation of D-dimer with no evidence of clinical [[thrombosis]].<ref name="pmid8238000">{{cite journal| author=Chen TY, Huang CC, Tsao CJ| title=Hemostatic molecular markers in nephrotic syndrome. | journal=Am J Hematol | year= 1993 | volume= 44 | issue= 4 | pages= 276-9 | pmid=8238000 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8238000 }} </ref><ref name="pmid15990160">{{cite journal| author=Singhal R, Brimble KS| title=Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management. | journal=Thromb Res | year= 2006 | volume= 118 | issue= 3 | pages= 397-407 | pmid=15990160 | doi=10.1016/j.thromres.2005.03.030 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15990160 }} </ref><ref name="pmid23221061">{{cite journal| author=Sexton DJ, Clarkson MR, Mazur MJ, Plant WD, Eustace JA| title=Serum D-dimer concentrations in nephrotic syndrome track with albuminuria, not estimated glomerular filtration rate. | journal=Am J Nephrol | year= 2012 | volume= 36 | issue= 6 | pages= 554-60 | pmid=23221061 | doi=10.1159/000345475 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23221061 }} </ref>
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| ===Sepsis and Septic Shock===
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| Normal 0 false false false EN-US X-NONE AR-SA
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|
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| D-dimer levels are almost always increased in patients with sepsis, septic shock, and disseminated intravascular coagulation (DIC). According to the Recombinant Human Activated Protein C Woldwide Evaluation in Severe Sepsis (PROWESS) trial that included 1,690 septic patients, D-dimer was elevated in approximately 100% of patients.<ref name="pmid11236773">{{cite journal| author=Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A et al.| title=Efficacy and safety of recombinant human activated protein C for severe sepsis. | journal=N Engl J Med | year= 2001 | volume= 344 | issue= 10 | pages= 699-709 | pmid=11236773 | doi=10.1056/NEJM200103083441001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11236773 }} </ref><ref name="pmid15025782">{{cite journal| author=Kinasewitz GT, Yan SB, Basson B, Comp P, Russell JA, Cariou A et al.| title=Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569]. | journal=Crit Care | year= 2004 | volume= 8 | issue= 2 | pages= R82-90 | pmid=15025782 | doi=10.1186/cc2459 | pmc=PMC420030 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15025782 }} </ref><ref name="pmid16781920">{{cite journal| author=Nguyen HB, Rivers EP, Abrahamian FM, Moran GJ, Abraham E, Trzeciak S et al.| title=Severe sepsis and septic shock: review of the literature and emergency department management guidelines. | journal=Ann Emerg Med | year= 2006 | volume= 48 | issue= 1 | pages= 28-54 | pmid=16781920 | doi=10.1016/j.annemergmed.2006.02.015 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16781920 }} </ref>
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| ===Surgery===
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|
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| ===Sickle Cell Disease===
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| ==ESC 2008 Guideline Recommendations <ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |title=Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>==
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| ===Suspected Non High-risk PE Patients (DO NOT EDIT)<ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |title=Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>===
| |
| {|class="wikitable"
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| |-
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| | colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
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| |-
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| | bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Plasma D-dimer measurement is recommended in emergency department patients to reduce the need for unnecessary imaging and irradiation, preferably with the use of a highly sensitive assay. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
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| |}
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|
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| ====Low Clinical Probability (DO NOT EDIT)<ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |title=Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>====
| |
| {|class="wikitable"
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| |-
| |
| | colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
| |
| |-
| |
| | bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Normal D-dimer level using either a highly or moderately sensitive assay excludes pulmonary embolism. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
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|
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| |}
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|
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| ====Intermediate Clinical Probability (DO NOT EDIT)<ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |title=Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>====
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| {|class="wikitable"
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| |-
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| | colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
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| |-
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| | bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' Normal D-dimer level using a highly sensitive assay excludes pulmonary embolism. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
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|
| |
| |}
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|
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| {|class="wikitable"
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| |-
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| | colspan="1" style="text-align:center; background:LemonChiffon"|[[European society of cardiology#Classes of Recommendations|Class IIa]]
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| |-
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| |bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Further testing should be considered if D-dimer level is normal when using a less sensitive assay. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
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|
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| |}
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| ====High Clinical Probability (DO NOT EDIT)<ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP |title=Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) |journal=Eur. Heart J. |volume=29|issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310|url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18757870 |accessdate=2011-12-07}}</ref>====
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| {|class="wikitable"
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| |-
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| |colspan="1" style="text-align:center; background:LightCoral"|[[European society of cardiology#Classes of Recommendations|Class III]]
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| |-
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| |bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' D-dimer measurement is not recommended in high clinical probability patients as a normal result does not safely exclude pulmonary embolism even when using a highly sensitive assay. ''([[European society of cardiology#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
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| |}
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| ==References==
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| {{reflist|2}}
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| [[Category:Laboratory Test]] | | [[Category:Laboratory Test]] |
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