D-dimer: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
 
(91 intermediate revisions by 2 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{SI}}
{{D-dimer}}
'''Editor(s)-In-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com], {{ATI}}; {{AE}} {{CZ}}


==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>


==Historical Perspective==
D-dimer testing was originally developed in the diagnosis of disseminated intravascular coagulation. In the [[1990s]], they turned out to be useful in diagnosing thromboembolic process.


==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]]).


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]] ==


[[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]] ==


[[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]]


==D-Dimer Test==
==Cinical Trials==
[[D-dimer landmark trials|Landmark Trials]]


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.
===Indications===
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.
For DVT and PE, there are various scoring systems that are used to determine the ''a priori'' clinical probability of these diseases; the best-known were introduced by Wells ''et al'' (2003).
* For a very high score, or pretest probability, a D-dimer will make little difference and [[anticoagulant]] therapy will be initiated regardless of test results, and additional testing for DVT or pulmonary embolism may be performed.
* For a moderate or low score, or pretest probability:<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>
** 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%
** 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. 
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>
===Reference Range===
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.
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>
===Types of Assays===
* [[ELISA]] (e.g. Vidas)
* Latex turbidimetric assay (automated immunoassay, e.g. Roche Tina-quant, MDA D-dimer)
* Enhanced microlatex
* Latex-enhanced photometric
* Whole Blood Agglutination (e.g. SimpliRED)
* Rapid Lateral Flow (e.g. Clearview Simplify)
===Test Properties===
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>
* [[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
* [[False negative]] readings can occur if the sample is taken either too early after thrombus formation or if testing is delayed for several days. Additionally, the presence of anti-coagulation can render the test negative because it prevents thrombus extension.
* Likelihood ratios are derived from sensitivity and specificity to adjust pretest probability.
== D-dimer and Thromboembolism==
=== Abnormal Levels ===
[[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>
=== Sensitivity and Specificity ===
====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>====
[[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]].
====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>====
[[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)''.
{| border="1"
|+
! Method !! Sensitivity (95% CI) !! Specificity (95% CI) !! Positive Likelihood Ratio (95% CI) !! Negative Likelihood Ratio (95% CI) !! Time to obtain Results
|-
| [[ELISA|Enzyme-linked immunosorbent assay (ELISA)]]
| align= "center" | 0.95 (0.85 to 1.00)
| align= "center" | NS
| align= "center" | NS
| align= "center" | 0.13 (0.03 to 0.58)
| align= "center" | ≥ 8 hours
|-
| [[ELISA|Quantitative rapid ELISA]]
| align= "center" | 0.95 (0.83 to 1.00)
| align= "center" | NS
| align= "center" | NS
| align= "center" | 0.13 (0.02 to 0.84)
| align= "center" | 30 mins
|-
| [[ELISA|Semi-Quantitative rapid ELISA]]
| align= "center" | 0.93 (0.79 to 1.00)
| align= "center" | NS
| align= "center" | NS
| align= "center" | 0.20 (0.04 to 0.96)
| align= "center" | 10 mins
|-
| [[ELISA|Qualitative rapid ELISA]]
| align= "center" | NS
| align= "center" | 0.68 (0.50 to 0.87)
| align= "center" | NS
| align= "center" | 0.11 (0.01 to 0.93)
| align= "center" | 10 mins
|-
| [[Latex agglutination test|Quantitative Latex Agglutination]]
| align= "center" | NS
| align= "center" | NS
| align= "center" | NS
| align= "center" | NS
| align= "center" | 10-15 mins
|-
| [[Latex agglutination test|Semi-quantitative Latex Agglutination]]
| align= "center" | NS
| align= "center" | NS
| align= "center" | NS
| align= "center" | 0.17 (0.04 to 0.78)
| align= "center" | 5 mins
|-
| [[Latex agglutination test|Whole-Blood Agglutination]]
| align= "center" | NS
| align= "center" | 0.74 (0.60 to 0.88)
| align= "center" | NS
| align= "center" | NS
| align= "center" | 2 mins
|}
=== Hemodynamically Stable Patients ===
====Incidence of Thromboembolic Events in Hemodynamically Stable Patients====
{| border="1"
|+
! Condition !! Incidence of thromboembolic event (%)
|-
| Patients not receiving anticoagulation with negative CT findings.
| 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>
|-
| Patients with a high d-dimer level
| 1.5%
|-
| Patients with a normal d-dimer level
| 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>
|}
*[[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>
*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>
=== Flowchart Summarizing the Role of D-dimer in the Diagnosis of PE ===
{{familytree/start |summary=Use of D-Dimer.}}
{{familytree | | | | GMa | GMa=Patients with suspection of [[Pulmonary embolism]]}}
{{familytree | |,|-|-|^|-|-|-|.| | | }}
{{familytree |JOE| | | | |SIS| | | JOE=Clinically Low or Moderate|SIS=Clinically High}}
{{familytree |,|^|-|.| | | | |!| }}
{{familytree |!| | |!| | | | |!| }}
{{familytree |!| | |ME| | |!|ME=D-Dimer Positive}}
{{familytree |!| | | |!| | | |!| }}
{{familytree |MOM| |!| | | |!| |MOM=D-Dimer Negative|}}
{{familytree | |!| | |!| | | |!| }}
{{familytree |GPa| |ME| |SIS|GPa=No treatment|ME=Further Tests|SIS=Further Tests}}
{{familytree/end}}
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>
==D-Dimer and Non Thromboembolism Conditions==
  Normal  0          false  false  false    EN-US  X-NONE  AR-SA
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>
==Aortic Dissection==
Normal  0          false  false  false    EN-US  X-NONE  AR-SA
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>
==Renal Disease==
Normal  0          false  false  false    EN-US  X-NONE  AR-SA
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 beless 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>
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>
==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>==
===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"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
|-
| 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>
|}
====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"
|-
| 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>
|}
====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>====
{|class="wikitable"
|-
| 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 a highly sensitive assay excludes pulmonary embolism. ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|}
{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[European society of cardiology#Classes of Recommendations|Class IIa]]
|-
|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>
|}
====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>====
{|class="wikitable"
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[European society of cardiology#Classes of Recommendations|Class III]]
|-
|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>
|}
==References==
{{reflist|2}}


[[Category:Laboratory Test]]
[[Category:Laboratory Test]]
Line 227: Line 24:
[[Category:Cardiology]]
[[Category:Cardiology]]
[[Category:Pulmonology]]
[[Category:Pulmonology]]
[[es:Dímero-D]]
[[id:D-dimer]]
[[nl:D-dimeer]]
[[ja:D-ダイマー]]
[[pt:Dímeros-D]]


{{WH}}
{{WH}}
{{WS}}
{{WS}}

Latest revision as of 12:53, 9 May 2014

D-Dimer Microchapters

Home

Patient information

Overview

Historical Perspective

Physiology

Clinical Correlation

Causes of High D-dimer

Diagnostic Role in Thromboembolism

Prognostic Role in Mortality

Prognostic Role in Thromboembolism Occurence

Prognostic Role in Thromboembolism Recurrence

Prognostic Role in Non-Thromboembolism

Clinical Trials

Landmark Trials

Case #1

D-dimer On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of D-dimer

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on D-dimer

CDC on D-dimer

D-dimer in the news

Blogs on D-dimer

Directions to Hospitals Treating D-dimer

Risk calculators and risk factors for D-dimer

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]


Overview

Historical Perspective

Physiology

Clinical Correlation

Causes of High D-dimer | Diagnostic Role in Thromboembolism | Prognostic Role in Mortality | Prognostic Role in Thromboembolism Occurrence | Prognostic Role in Thromboembolism Recurrence | Prognostic Role in Non-Thromboembolism

Cinical Trials

Landmark Trials

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=D-dimer&oldid=969645"