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==Overview==
==Overview==
D-dimer is used in the diagnosis of [[deep vein thrombosis]] among patients with low or unlikely probability of [[venous thromboembolism]].<ref name="pmid16403932">{{cite journal| author=Wells PS, Owen C, Doucette S, Fergusson D, Tran H| title=Does this patient have deep vein thrombosis? | journal=JAMA | year= 2006 | volume= 295 | issue= 2 | pages= 199-207 | pmid=16403932 | doi=10.1001/jama.295.2.199 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16403932  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213132 Review in: Evid Based Med. 2006 Aug;11(4):119]  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16813372 Review in: ACP J Club. 2006 Jul-Aug;145(1):24] </ref><ref name="pmid11453709">{{cite journal| author=Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D et al.| title=Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 2 | pages= 98-107 | pmid=11453709 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11453709  }} </ref>  While 500 ng/mL has long been the most commonly used cut off value for abnormal D-dimer concentration, recent studies suggest the use of an age adjusted cut-off concentration of D-dimer.  The age adjusted cut-off value of D-dimer is 500 ng/mL for subjects whose age is less than 50 years, and the age multiplied by 10 for subjects older than 50 years.<ref name="pmid22511491">{{cite journal| author=Douma RA, Tan M, Schutgens RE, Bates SM, Perrier A, Legnani C et al.| title=Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded. | journal=Haematologica | year= 2012 | volume= 97 | issue= 10 | pages= 1507-13 | pmid=22511491 | doi=10.3324/haematol.2011.060657 | pmc=PMC3487551 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22511491  }} </ref><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="JAMA 2014"> Righini M, Van Es J, Den Exter PL, et al. Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism: The ADJUST-PE Study. JAMA. 2014;311(11):1117-1124. doi:10.1001/jama.2014.2135. </ref>
D-dimer is used in the diagnosis of [[deep vein thrombosis]] among patients with low or unlikely probability of [[venous thromboembolism]].<ref name="pmid16403932">{{cite journal| author=Wells PS, Owen C, Doucette S, Fergusson D, Tran H| title=Does this patient have deep vein thrombosis? | journal=JAMA | year= 2006 | volume= 295 | issue= 2 | pages= 199-207 | pmid=16403932 | doi=10.1001/jama.295.2.199 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16403932  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17213132 Review in: Evid Based Med. 2006 Aug;11(4):119]  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16813372 Review in: ACP J Club. 2006 Jul-Aug;145(1):24] </ref><ref name="pmid11453709">{{cite journal| author=Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D et al.| title=Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. | journal=Ann Intern Med | year= 2001 | volume= 135 | issue= 2 | pages= 98-107 | pmid=11453709 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11453709  }} </ref>  While 500 ng/mL has long been the most commonly used cut off value for abnormal D-dimer concentration, recent studies suggest the use of an age adjusted cut-off concentration of D-dimer.  The age adjusted cut-off value of D-dimer is 500 ng/mL for subjects whose age is less than 50 years, and the age multiplied by 10 for subjects older than 50 years.<ref name="pmid22511491">{{cite journal| author=Douma RA, Tan M, Schutgens RE, Bates SM, Perrier A, Legnani C et al.| title=Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded. | journal=Haematologica | year= 2012 | volume= 97 | issue= 10 | pages= 1507-13 | pmid=22511491 | doi=10.3324/haematol.2011.060657 | pmc=PMC3487551 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22511491  }} </ref><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="pmid24643601">{{cite journal| author=Righini M, Van Es J, Den Exter PL, Roy PM, Verschuren F, Ghuysen A et al.| title=Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. | journal=JAMA | year= 2014 | volume= 311 | issue= 11 | pages= 1117-24 | pmid=24643601 | doi=10.1001/jama.2014.2135 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24643601  }} </ref>


==Laboratory Findings==
==Laboratory Findings==
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'''For a detailed discussion on D-dimer, please click '''[[D-dimer|here]]'''.'''
'''For a detailed discussion on D-dimer, please click '''[[D-dimer|here]]'''.'''


[[D-dimer]] is a cross-linked [[fibrin degradation product]] and a marker of endogenous [[fibrinolysis]]. In the setting of ongoing thrombosis, D-dimer's concentration is elevated in the blood and thus makes it a screening tool to rule out [[DVT]].
* [[D-dimer]] is a cross-linked [[fibrin degradation product]] and a marker of endogenous [[fibrinolysis]]. In the setting of ongoing thrombosis, D-dimer's concentration is elevated in the blood and thus makes it a screening tool to rule out [[DVT]].


D-dimer is the "test of choice" in patients who are considered to be "low risk" according to [[Wells score for DVT|pre-test probability]].  D-dimer is more useful if its negative rather than positive. It has a great '''negative predictive value''' in low to moderate risk patients of DVT.  If D-dimer is elevated, then [[DVT]] should be confirmed with [[Deep vein thrombosis ultrasound|ultrasound]].<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}}</ref><ref name="pmid12755550">{{cite journal |author=Bates SM, Kearon C, Crowther M, ''et al'' |title=A diagnostic strategy involving a quantitative latex D-dimer assay reliably excludes deep venous thrombosis |journal=Ann. Intern. Med. |volume=138 |issue=10 |pages=787-94 |year=2003 |pmid=12755550 |doi=}}</ref>
* D-dimer is the "test of choice" in patients who are considered to be "low risk" according to [[Wells score for DVT|pre-test probability]].  D-dimer is more useful if its negative rather than positive. It has a great '''negative predictive value''' in low to moderate risk patients of DVT.  If D-dimer is elevated, then [[DVT]] should be confirmed with [[Deep vein thrombosis ultrasound|ultrasound]].<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}}</ref><ref name="pmid12755550">{{cite journal |author=Bates SM, Kearon C, Crowther M, ''et al'' |title=A diagnostic strategy involving a quantitative latex D-dimer assay reliably excludes deep venous thrombosis |journal=Ann. Intern. Med. |volume=138 |issue=10 |pages=787-94 |year=2003 |pmid=12755550 |doi=}}</ref>


The cut off value for abnormal D-dimer concentration is 500 ng/mL.  Interpretation of D-dimer may be improved by using age adjusted levels:<ref name="pmid24643601">{{cite journal| author=Righini M, Van Es J, Den Exter PL, Roy PM, Verschuren F, Ghuysen A et al.| title=Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. | journal=JAMA | year= 2014 | volume= 311 | issue= 11 | pages= 1117-24 | pmid=24643601 | doi=10.1001/jama.2014.2135 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24643601  }} </ref>
* The cut off value for abnormal D-dimer concentration is 500 ng/mL.  Interpretation of D-dimer may be improved by using age adjusted levels:<ref name="pmid22511491">{{cite journal| author=Douma RA, Tan M, Schutgens RE, Bates SM, Perrier A, Legnani C et al.| title=Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded. | journal=Haematologica | year= 2012 | volume= 97 | issue= 10 | pages= 1507-13 | pmid=22511491 | doi=10.3324/haematol.2011.060657 | pmc=PMC3487551 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22511491  }} </ref><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="pmid24643601">{{cite journal| author=Righini M, Van Es J, Den Exter PL, Roy PM, Verschuren F, Ghuysen A et al.| title=Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. | journal=JAMA | year= 2014 | volume= 311 | issue= 11 | pages= 1117-24 | pmid=24643601 | doi=10.1001/jama.2014.2135 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24643601  }} </ref>
* Patients less than 50 years old: normal D-dimer is less than 500 µg/L
** Patients less than 50 years old: normal D-dimer is less than 500 µg/L
* In patients 50 years or older: normal D-dimer is adjusted to be age multiplied by 10
** In patients 50 years or older: normal D-dimer is adjusted to be age multiplied by 10


====Specificity and Sensitivity====
====Specificity and Sensitivity====

Revision as of 14:54, 17 July 2014
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Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2] ; Kashish Goel, M.D.; Assistant Editor(s)-In-Chief: Justine Cadet

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Overview

D-dimer is used in the diagnosis of deep vein thrombosis among patients with low or unlikely probability of venous thromboembolism.[1][2] While 500 ng/mL has long been the most commonly used cut off value for abnormal D-dimer concentration, recent studies suggest the use of an age adjusted cut-off concentration of D-dimer. The age adjusted cut-off value of D-dimer is 500 ng/mL for subjects whose age is less than 50 years, and the age multiplied by 10 for subjects older than 50 years.[3][4][5]

Laboratory Findings

D-Dimer

For a detailed discussion on D-dimer, please click here.

  • D-dimer is the "test of choice" in patients who are considered to be "low risk" according to pre-test probability. D-dimer is more useful if its negative rather than positive. It has a great negative predictive value in low to moderate risk patients of DVT. If D-dimer is elevated, then DVT should be confirmed with ultrasound.[6][7]
  • The cut off value for abnormal D-dimer concentration is 500 ng/mL. Interpretation of D-dimer may be improved by using age adjusted levels:[3][4][5]
    • Patients less than 50 years old: normal D-dimer is less than 500 µg/L
    • In patients 50 years or older: normal D-dimer is adjusted to be age multiplied by 10

Specificity and Sensitivity

A large number of D-dimer assays are available and may vary in-between hospitals. In a meta-analysis of 217 studies involving DVT patients, the sensitivities of the D-dimer enzyme-linked immunofluorescence assay (ELFA) (96%), micro plate enzyme-linked immunosorbent assay (94%), and latex quantitative assay (93%; PE 95%) were superior to the whole-blood D-dimer assay (83%), and latex qualitative assay (69%). Because of this, ELISA assays are termed as "highly sensitive" and whole blood D-dimer assays is "moderately sensitive". Thus, D-dimer has a high sensitivity (sNOUT) and low specificity (sPIN) for DVT. This means that D-dimer is a better test for "ruling out" DVT rather than "ruling in".

D-dimer Elevation in Other Conditions

D-dimer can be elevated in following conditions, which should be kept in mind while assessing this biomarker in patients with suspected DVT:

Workup for Hypercoagulation

References

  1. ↑ Wells PS, Owen C, Doucette S, Fergusson D, Tran H (2006). "Does this patient have deep vein thrombosis?". JAMA. 295 (2): 199–207. doi:10.1001/jama.295.2.199. PMID 16403932. Review in: Evid Based Med. 2006 Aug;11(4):119 Review in: ACP J Club. 2006 Jul-Aug;145(1):24
  2. ↑ Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D; et al. (2001). "Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer". Ann Intern Med. 135 (2): 98–107. PMID 11453709.
  3. ↑ 3.0 3.1 Douma RA, Tan M, Schutgens RE, Bates SM, Perrier A, Legnani C; et al. (2012). "Using an age-dependent D-dimer cut-off value increases the number of older patients in whom deep vein thrombosis can be safely excluded". Haematologica. 97 (10): 1507–13. doi:10.3324/haematol.2011.060657. PMC 3487551. PMID 22511491.
  4. ↑ 4.0 4.1 Schouten HJ, Geersing GJ, Koek HL, Zuithoff NP, Janssen KJ, Douma RA; et al. (2013). "Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis". BMJ. 346: f2492. doi:10.1136/bmj.f2492. PMC 3643284. PMID 23645857.
  5. ↑ 5.0 5.1 Righini M, Van Es J, Den Exter PL, Roy PM, Verschuren F, Ghuysen A; et al. (2014). "Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study". JAMA. 311 (11): 1117–24. doi:10.1001/jama.2014.2135. PMID 24643601.
  6. ↑ Wells PS, Anderson DR, Rodger M; et al. (2003). "Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis". N. Engl. J. Med. 349 (13): 1227–35. doi:10.1056/NEJMoa023153. PMID 14507948.
  7. ↑ Bates SM, Kearon C, Crowther M; et al. (2003). "A diagnostic strategy involving a quantitative latex D-dimer assay reliably excludes deep venous thrombosis". Ann. Intern. Med. 138 (10): 787–94. PMID 12755550.

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