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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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| * Increase level of D-dimer is correlated with worsening severity and death. For instance, according to one study 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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| * On the other hand, its decrease was associated with resolution of sepsis.<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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| igher 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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| 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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| * D-dimer levels may be elevated after [[surgery]] and [[trauma]] independent of [[VTE]] and [[PE]]. The diagnosis of post-operative VTE, a common complication following surgery, becomes even a more challenging diagnosis for this specific subset of patients given the unpredictable and heterogeneous variation of post-operative D-dimer levels. The dynamics behind D-dimer elevation following surgery and trauma are poorly understood.<ref name="pmid11833854">{{cite journal| author=Lippi G, Veraldi GF, Fraccaroli M, Manzato F, Cordiano C, Guidi G| title=Variation of plasma D-dimer following surgery: implications for prediction of postoperative venous thromboembolism. | journal=Clin Exp Med | year= 2001 | volume= 1 | issue= 3 | pages= 161-4 | pmid=11833854 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11833854 }} </ref>
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| * In a study of 154 patients categorized according to different types of abdominal surgeries, surgeries that did not include entering the abdominal cavity did not reveal elevation in D-dimer. In contrast, approximately 44% of open and laparoscopic intra-abdominal and retroperitoneal (and liver) surgeries were associated with elevated D-dimer levels that normalized after 25 and 38 days post-operatively respectively. D-dimer was found to generally peak around day 7 post-operation. The right time post-operatively to use D-dimer without the effect of the surgery itself is yet to be determined, but believed to be more than 5 weeks following intra-abdominal and retroperitoneal. It is thought that following peak, D-dimer levels decline at a rate of 6% every day.( PMID: 19474701 - Dindo et al. 200). The length of the surgery was associated with the elevation of D-dimer. However, no cut-off surgery length is determined.<ref name="pmid19474701">{{cite journal| author=Dindo D, Breitenstein S, Hahnloser D, Seifert B, Yakarisik S, Asmis LM et al.| title=Kinetics of D-dimer after general surgery. | journal=Blood Coagul Fibrinolysis | year= 2009 | volume= 20 | issue= 5 | pages= 347-52 | pmid=19474701 | doi=10.1097/MBC.0b013e32832a5fe6 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19474701 }} </ref>
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| * Orthopedic surgeries are also associated with an increase in D-dimer levels. In a study that recruited 78 patients with cemented or hybrid total hip replacement and uncemented total knee replacement. During the first 7 days post-op, D-dimers were significantly elevated particularly on day 1 and 7 post-operatively, showing a double-peak distribution.<ref name="pmid12181657">{{cite journal| author=Shiota N, Sato T, Nishida K, Matsuo M, Takahara Y, Mitani S et al.| title=Changes in LPIA D-dimer levels after total hip or knee arthroplasty relevant to deep-vein thrombosis diagnosed by bilateral ascending venography. | journal=J Orthop Sci | year= 2002 | volume= 7 | issue= 4 | pages= 444-50 | pmid=12181657 | doi=10.1007/s007760200077 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12181657 }} </ref><ref name="pmid18325211">{{cite journal| author=Rafee A, Herlikar D, Gilbert R, Stockwell RC, McLauchlan GJ| title=D-Dimer in the diagnosis of deep vein thrombosis following total hip and knee replacement: a prospective study. | journal=Ann R Coll Surg Engl | year= 2008 | volume= 90 | issue= 2 | pages= 123-6 | pmid=18325211 | doi=10.1308/003588408X261627 | pmc=PMC2443306 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18325211 }} </ref>
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| ===Sickle Cell Disease===
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| Normal 0 false false false EN-US X-NONE AR-SA
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| The pathogenesis and clinical manifestations of sickle cell disease are mostly related to its hypercoagulable sickle-shaped red blood cells that contain phosphatydil serine moieties that contribute to their thrombogenic nature. In addition, endothelial dysfunction, sluggish blood flow, and increased transit time, all of which are associated with generation of subclinical or clinically relevant thrombin, are all factors generally augmented in patients with sickle cell disease. Elevated D-dimer levels is commonly found in up to 68% of homozygous sickle cell disease patients experiencing sickling crises and frequently associated with abnormal chest xray (CXR) findings.<ref name="pmid21063468">{{cite journal| author=Dar J, Mughal I, Hassan H, Al Mekki TE, Chapunduka Z, Hassan IS| title=Raised D-dimer levels in acute sickle cell crisis and their correlation with chest X-ray abnormalities. | journal=Ger Med Sci | year= 2010 | volume= 8 | issue= | pages= Doc25 | pmid=21063468 | doi=10.3205/000114 | pmc=PMC2975260 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21063468 }} </ref><ref name="pmid11719358">{{cite journal| author=Setty BN, Rao AK, Stuart MJ| title=Thrombophilia in sickle cell disease: the red cell connection. | journal=Blood | year= 2001 | volume= 98 | issue= 12 | pages= 3228-33 | pmid=11719358 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11719358 }} </ref>
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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>===
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| {|class="wikitable"
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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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| | 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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| ====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>====
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| {|class="wikitable"
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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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| | 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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| ====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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| | colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
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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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| {|class="wikitable"
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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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| |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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| ====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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| |colspan="1" style="text-align:center; background:LightCoral"|[[European society of cardiology#Classes of Recommendations|Class III]]
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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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| ==References==
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| {{reflist|2}}
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| [[Category:Laboratory Test]] | | [[Category:Laboratory Test]] |
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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}} |