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D-dimer in plasma (SimpliRED)

Specific immunoassays for D-dimer can be performed directly on patient plasma. Plasma D-dimer levels reflect in vivo fibrinolysis. Indications: 1) evaluation of suspected deep vein thrombosis 2) assessment of risk for recurrence of DVT after cessation of anticoagulaton [11,13] 3) evaluation of suspected pulmonary embolism 4) evaluation of suspected aortic dissection Normal range: - < 250-500 ug/L; < 0.5 mg/L, < 0.5 ug/mL [22] - threshold to rule out DVT/PE (specificity 47%) - < 500 ug/L; < 0.5 mg/L, < 0.5 ug/mL [22] - < 750 ug/L if >= 60 years of age [14] - age x 10 in ug/L [15,18,19]* * use of age-associated threshold reduces need for pulmonary CT angiogram [19] Clinical significance: - cross-linked D-dimer fragment of fibrin produced during fibrinolysis - formation of D-dimer requires the action of both thrombin & plasmin - plasmin degradation of fibrinogen alone does not result in D-dimer formation. - increases in D-dimer occur with thromboembolism a) Specificity 63% for DVT [3] b) Specificity of test for thrombosis is reduced in elderly to < 10% for patients > 80 years of age. c) Sensitivity 81-88% for pulmonary embolism [4] 1] 93% in segmental or larger arteries 2] 50% in subsegmental or smaller arteries d) Specificity 52-61% for pulmonary embolism [4] - D-dimer adjusted for clinical probability in diagnosis of pulmonary embolism [21] - < 1000 ng/mL for low-risk patients - result in normal range does NOT rule out pulmonary embolism in patient with high pretest probablity [10] - Ref [8] concludes D-dimer of limited clinical utlilty for diagnosis of pulmonary embolism. - Sensitivity 100% for DVT in pregnant women [12] - a thrombosis without elevated D-dimer is rare (< 2-3%) - for patients with a 1st DVT, a plasma D-dimer < 250 ng/mL measured 3 weeks after cessation of anticoagulation indicates low probability of recurrent DVT (3.7% vs 11.5 % 2 year risk, relative risk 0.3) vs plasma D-dimer > 750 ng/mL [6] - strategy of D-dimer testing & selective ultrasound as effective in the diagnosis of DVT as ultrasound for all R/O DVT [7] (strategy dependent upon high pre-test probability of DVT for selecting patients for ultrasound) - plasma D-dimer > 273 ng/mL (highest quartile) after MI* or unstable angina associated with increased 6 year risk of cardiovascular event & VTE* & 16 year risk of all-cause mortality, cardiovascular mortality & cancer mortality [20] (observation seems independent of statin administration) * MI=myocardial infarction, VTE=venous_thromboembolism Increases: 1) primary & secondary fibrinolysis 2) thrombolytic therapy with tissue plasminogen activator (tPA) 3) thrombosis (use 500 ng/mL for cutoff) a) deep vein thrombosis (DVT) [9] b) pulmonary embolism c) arterial thromboembolism d) disseminated intravascular coagulation (DIC) e) localized intravascular coagulation f) plasma D-dimer > 750 ng/mL after cessation of anticoagulation predicts recurrence of DVT [11,13] 4) vaso-occlusive crisis of sickle cell disease 5) pregnancy, especially post-partum period 6) malignancy 7) surgery 8) liver disease 9) infection 10) inflammation 11) hematoma 12) old age Method: 1) agglutination of D-dimer with monoclonal antibody fixed onto latex beads 2) test read as macroscopic agglutination 3) fibrinogen & fibrin split products do NOT react 4) turn-around time 30 minutes [3] Specimen: 1) plasma (citrate) 2) stable for 8 hours at room temperature 3) stable for 6 months at -20 degrees C

Related

D-dimer in plasma (SimpliRED) intravascular coagulation

Specific

fibrin D-dimer DDU in plasma fibrin D-dimer FEU in plasma

General

fibrin degradation products in plasma; fibrin split products in plasma (FDP, FSP)

References

  1. Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 728
  2. Perrier et al Lancet 353:190, 1999
  3. bioMerieux Inc, Hazelwood MO 63042, (314) 731-8500
  4. Journal Watch 22(7):57, 2002 de Monye W, Sanson BJ, Buller HR, Pattynama PM, Huisman MV; ANTELOPE Study Group. The performance of two rapid quantitative D-dimer assays in 287 patients with clinically suspected pulmonary embolism. Thromb Res. 2002 Sep 15;107(6):283-6. PMID: 12565714 - De Monye W, Sanson BJ, Mac Gillavry MR, Pattynama PM, Buller HR, van den Berg-Huysmans AA, Huisman MV; ANTELOPE-Study Group. Embolus location affects the sensitivity of a rapid quantitative D-dimer assay in the diagnosis of pulmonary embolism. Am J Respir Crit Care Med. 2002 Feb 1;165(3):345-8. PMID: 11818319
  5. Journal Watch 23(14):116, 2003 Bates SM et al, Ann Intern Med 138:787, 2003
  6. Journal Watch 23(19):149, 2003 Eichinger S et al, JAMA 290:1071, 2003
  7. Journal Watch 23(21):165, 2003 Wells PS et al, N Engl J Med 349:1227, 2003 PMID: 14507948
  8. Rathbun SW, Whitsett TL, Vesely SK, Raskob GE. Clinical utility of D-dimer in patients with suspected pulmonary embolism and nondiagnostic lung scans or negative CT findings. Chest. 2004 Mar;125(3):851-5. PMID: 15006941
  9. Journal Watch 25(3):23, 2005 Rathbun SW, Whitsett TL, Raskob GE. Negative D-dimer result to exclude recurrent deep venous thrombosis: a management trial. Ann Intern Med. 2004 Dec 7;141(11):839-45. Summary for patients in: Ann Intern Med. 2004 Dec 7;141(11):I46. PMID: 15583225
  10. Karbrhel C et al, A highly sensitive ELISA D-dimer increases testing, but not diagnosis of pulmonary embolism. Acad Emerg Med 2006; 13:519 PMID: 16551779
  11. Palareti G et al for the PROLONG investigators. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 2006, 355:1780 PMID: 17065639
  12. Chan WS, Chunilal S, Lee A, Crowther M, Rodger M, Ginsberg JS. A red blood cell agglutination D-dimer test to exclude deep venous thrombosis in pregnancy. Ann Intern Med. 2007 Aug 7;147(3):165-70. PMID: 17679704
  13. Verhovsek M et al. Systematic review: D-dimer to predict recurrent disease after stopping anticoagulant therapy for unprovoked venous thromboembolism. Ann Intern Med 2008 Oct 7; 149:481. PMID: 18838728
  14. Schouten HJ et al Validation of two age dependent D-dimer cut-off values for exclusion of deep vein thrombosis in suspected elderly patients in primary care: retrospective, cross sectional, diagnostic analysis BMJ 2012;344:e2985 PMID: 22674922 http://www.bmj.com/content/344/bmj.e2985
  15. Schouten HJ et al. 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 2013 May 3; 346:f2492 PMID: 23645857
  16. D-Dimer Laboratory Test Directory ARUP: 30057
  17. Venous Thromboembolism, Qual Laboratory Test Directory ARUP: 30070
  18. Righini M et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: The ADJUST-PE Study. JAMA 2014 Mar 19; 311:1117 PMID: 24643601 http://jama.jamanetwork.com/article.aspx?articleid=1841967
  19. Sharp AL et al. An age-adjusted D-dimer threshold for emergency department patients with suspected pulmonary embolus: Accuracy and clinical implications. Ann Emerg Med 2015 Aug 27 PMID: 26320520 http://www.annemergmed.com/article/S0196-0644%2815%2900616-2/abstract
  20. Stiles S D-Dimer Predicts CV, Cancer Mortality Over 16 Years in Patients With Stable CHD. Medscape - Jan 26, 2018. https://www.medscape.com/viewarticle/891884 - Simes J, Robledo KP, White HD et al D-dimer Predicts Long-Term Cause-Specific Mortality, Cardiovascular Events and Cancer in Stable Coronary Heart Disease Patients: The LIPID Study.. Circulation. 2018 Jan 24. [Epub ahead of print] PMID: 29367425
  21. Kearon C et sl Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability. N Engl J Med 2019; 381:2125-2134, Nov 28 PMID: 31774957 https://www.nejm.org/doi/full/10.1056/NEJMoa1909159
  22. Medical Knowledge Self Assessment Program (MKSAP) 19 American College of Physicians, Philadelphia 2022

Component-of

DIC panel