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11/9/2013 D-dimer - Wikipedia, the free encyclopedia
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DdimerFrom Wikipedia, the free encyclopedia
Ddimer is a fibrin degradation product (or FDP), a small protein fragment present in the blood after ablood clot is degraded by fibrinolysis. It is so named because it contains two crosslinked D fragments ofthe fibrin protein.[1]
Ddimer concentration may be determined by a blood test to help diagnose thrombosis. Since itsintroduction in the 1990s, it has become an important test performed in patients suspected of thromboticdisorders. While a negative result practically rules out thrombosis, a positive result can indicate thrombosisbut does not rule out other potential causes. Its main use, therefore, is to exclude thromboembolic diseasewhere the probability is low. In addition, it is used in the diagnosis of the blood disorder disseminatedintravascular coagulation.[1]
Contents
1 Principles2 Indications3 Test properties4 History5 References
Principles
Coagulation, the formation of a blood clot or thrombus, occurs when the proteins of the coagulationcascade are activated, either by contact with damaged blood vessel wall (intrinsic pathway) or byactivation of factor VII by tissue activating factors. Both pathways lead to the generation of thrombin, anenzyme that turns the soluble blood protein fibrinogen into fibrin, which aggregates into proteofibrils.Another thrombingenerated enzyme, factor XIII, then crosslinks the fibrin proteofibrils at the D fragmentsite, leading to the formation of an insoluble gel which serves as a scaffold for blood clot formation.[1]
The circulating enzyme plasmin, the main enzyme of fibrinolysis, cleaves the fibrin gel in a number ofplaces. The resultant fragments, "high molecular weight polymers", are digested several times more byplasmin to lead to intermediate and then to small polymers (fibrin degradation products or FDPs). Thecrosslink between two D fragments remains intact, however, and these are exposed on the surface whenthe fibrin fragments are sufficiently digested. The typical Ddimer containing fragment contains two Ddomains and one E domain of the original fibrinogen molecule.[1]
Ddimers are not normally present in human blood plasma, except when the coagulation system has beenactivated, for instance because of the presence of thrombosis or disseminated intravascular coagulation.The Ddimer assay depends on the binding of a monoclonal antibody to a particular epitope on the Ddimer fragment. Several detection kits are commercially available; all of them rely on a differentmonoclonal antibody against Ddimer. For some of these, the area of the Ddimer to which the antibodybinds is known. The binding of the antibody is then measured quantitatively by one of various laboratorymethods.[1]
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Principles of Ddimer testing
Indications
Ddimer testing is of clinical use when there is a suspicion of deep venous thrombosis (DVT), pulmonaryembolism (PE) or disseminated intravascular coagulation (DIC).[2] It is under investigation in the diagnosisof aortic dissection.[3][4]
For DVT and PE, there are possible various scoring systems that are used to determine the a priori clinicalprobability of these diseases; the bestknown were introduced by Wells et al. (2003).
For a very high score, or pretest probability, a Ddimer will make little difference and anticoagulanttherapy will be initiated regardless of test results, and additional testing for DVT or pulmonaryembolism may be performed.For a moderate or low score, or pretest probability:[5]
A negative Ddimer test will virtually rule out thromboembolism: the degree to which the Ddimer reduces the probability of thrombotic disease is dependent on the test properties of thespecific test used in the clinical setting: most available Ddimer tests with a negative result willreduce the probability of thromboembolic disease to less than 1% if the pretest probability isless than 1520%If the Ddimer reads high, then further testing (ultrasound of the leg veins or lung scintigraphyor CT scanning) is required to confirm the presence of thrombus. Anticoagulant therapy maybe started at this point or withheld until further tests confirm the diagnosis, depending on theclinical situation.
In some hospitals, they are measured bylaboratories after a form is completedshowing the probability score and only ifthe probability score is low orintermediate. This reduces the need forunnecessary tests in those who are highprobability.[6] Performing the Ddimer testfirst can avoid a significant proportion ofimaging tests and is less invasive. Sincethe Ddimer can exclude the need forimaging, specialty professionalorganizations recommend that physiciansuse Ddimer testing as an initialdiagnostic.[7][8][9][10]
Test properties
Various kits have a 9395% sensitivity andabout 50% specificity in the diagnosis ofthrombotic disease.[11]
False positive readings can be dueto various causes: liver disease, highrheumatoid factor, inflammation,malignancy, trauma, pregnancy,recent surgery as well as advanced
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age[citation needed]False negative readings can occur if the sample is taken either too early after thrombus formation orif testing is delayed for several days. Additionally, the presence of anticoagulation can render thetest negative because it prevents thrombus extension.False values may be obtained if the specimen collection tube is not sufficiently filled (false low valueif underfilled and false high value if overfilled). This is due to the dilutional effect of theanticoagulant (the blood must be collected in a 9:1 blood to anticoagulant ratio).Likelihood ratios are derived from sensitivity and specificity to adjust pretest probability.
In interpretation of the ddimer, for patients over age 50 a value of ageX10 may be abnormal.[12][13]
History
Ddimer was originally described in the 1970s, and found its diagnostic application in the 1990s.[1]
References
1. ^ a b c d e f Adam SS, Key NS, Greenberg CS (March 2009). "Ddimer antigen: current concepts and futureprospects" (http://bloodjournal.hematologylibrary.org/cgi/content/full/113/13/2878). Blood 113 (13): 2878–2887. doi:10.1182/blood200806165845 (http://dx.doi.org/10.1182%2Fblood200806165845).PMID 19008457 (//www.ncbi.nlm.nih.gov/pubmed/19008457).
2. ^ General Practice Notebook > Ddimer (http://www.gpnotebook.co.uk/simplepage.cfm?ID=26869806)Retrieved September 2011
3. ^ Suzuki, T.; Distante, A.; Eagle, K. (2010). "Biomarkerassisted diagnosis of acute aortic dissection: How farwe have come and what to expect". Current Opinion in Cardiology 25 (6): 541–545.doi:10.1097/HCO.0b013e32833e6e13 (http://dx.doi.org/10.1097%2FHCO.0b013e32833e6e13).PMID 20717014 (//www.ncbi.nlm.nih.gov/pubmed/20717014).
4. ^ Ranasinghe, A. M.; Bonser, R. S. (2010). "Biomarkers in Acute Aortic Dissection and Other AorticSyndromes". Journal of the American College of Cardiology 56 (19): 1535–1541.doi:10.1016/j.jacc.2010.01.076 (http://dx.doi.org/10.1016%2Fj.jacc.2010.01.076). PMID 21029872(//www.ncbi.nlm.nih.gov/pubmed/21029872).
5. ^ Wells PS, Anderson DR, Rodger M et al. (2003). "Evaluation of Ddimer in the diagnosis of suspected deepvein thrombosis" (http://content.nejm.org/cgi/content/full/349/13/1227). N. Engl. J. Med. 349 (13): 1227–1235. doi:10.1056/NEJMoa023153 (http://dx.doi.org/10.1056%2FNEJMoa023153). PMID 14507948(//www.ncbi.nlm.nih.gov/pubmed/14507948).
6. ^ Rathbun, SW; TL Whitsett, SK Vesely, GE Raskob (2004). "Clinical utility of Ddimer in patients withsuspected pulmonary embolism and nondiagnostic lung scans or negative CT findings". Chest 125 (3): 851–855. doi:10.1378/chest.125.3.851 (http://dx.doi.org/10.1378%2Fchest.125.3.851). PMC 1215466(//www.ncbi.nlm.nih.gov/pmc/articles/PMC1215466). PMID 15006941(//www.ncbi.nlm.nih.gov/pubmed/15006941).
7. ^ American College of Physicians, "Five Things Physicians and Patients Should Question"(http://choosingwisely.org/wpcontent/uploads/2012/04/5things_12_factsheet_Amer_College_Phys.pdf),presented by ABIM Foundation, Choosing Wisely (American College of Physicians), retrieved August 14, 2012
8. ^ Fesmire, F. M.; Brown, M. D.; Espinosa, J. A.; Shih, R. D.; Silvers, S. M.; Wolf, S. J.; Decker, W. W.;American College of Emergency Physicians (2011). "Critical Issues in the Evaluation and Management ofAdult Patients Presenting to the Emergency Department with Suspected Pulmonary Embolism". Annals ofEmergency Medicine 57 (6): 628–652.e75. doi:10.1016/j.annemergmed.2011.01.020(http://dx.doi.org/10.1016%2Fj.annemergmed.2011.01.020). PMID 21621092(//www.ncbi.nlm.nih.gov/pubmed/21621092).
9. ^ Torbicki, A.; Perrier, A.; Konstantinides, S.; Agnelli, G.; Galiè, N.; Pruszczyk, P.; Bengel, F.; Brady, A. J.B.; Ferreira, D.; Janssens, U.; Klepetko, W.; Mayer, E.; RemyJardin, M.; Bassand, J. P.; Vahanian, A.;Camm, J.; De Caterina, R.; Dean, V.; Dickstein, K.; Filippatos, G.; FunckBrentano, C.; Hellemans, I.;
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Kristensen, S. D.; McGregor, K.; Sechtem, U.; Silber, S.; Tendera, M.; Widimsky, P.; Zamorano, J. L.;Zamorano, J. L. (2008). "Guidelines on the diagnosis and management of acute pulmonary embolism: TheTask Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society ofCardiology (ESC)". European Heart Journal 29 (18): 2276–2315. doi:10.1093/eurheartj/ehn310(http://dx.doi.org/10.1093%2Feurheartj%2Fehn310). PMID 18757870(//www.ncbi.nlm.nih.gov/pubmed/18757870).
10. ^ Qaseem, A.; Snow, V.; Barry, P.; Hornbake, E. R.; Rodnick, J. E.; Tobolic, T.; Ireland, B.; Segal, J.; Bass,E.; Weiss, K. B.; Green, L.; Owens, D. K. (2007). "Current Diagnosis of Venous Thromboembolism inPrimary Care: A Clinical Practice Guideline from the American Academy of Family Physicians and theAmerican College of Physicians". The Annals of Family Medicine 5: 57. doi:10.1370/afm.667(http://dx.doi.org/10.1370%2Fafm.667).
11. ^ Schrecengost JE, LeGallo RD, Boyd JC et al. (September 2003). "Comparison of diagnostic accuracies inoutpatients and hospitalized patients of Ddimer testing for the evaluation of suspected pulmonary embolism".Clinical Chemistry 49 (9): 1483–1490. doi:10.1373/49.9.1483 (http://dx.doi.org/10.1373%2F49.9.1483).PMID 12928229 (//www.ncbi.nlm.nih.gov/pubmed/12928229).
12. ^ van Es J, Mos I, Douma R, Erkens P, Durian M, Nizet T et al. (2012). "The combination of four differentclinical decision rules and an ageadjusted Ddimer cutoff increases the number of patients in whom acutepulmonary embolism can safely be excluded." (http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22072293). Thromb Haemost 107(1): 167–71. doi:10.1160/TH11080587 (http://dx.doi.org/10.1160%2FTH11080587). PMID 22072293(//www.ncbi.nlm.nih.gov/pubmed/22072293).
13. ^ Douma RA, le Gal G, Söhne M, Righini M, Kamphuisen PW, Perrier A et al. (2010). "Potential of an ageadjusted Ddimer cutoff value to improve the exclusion of pulmonary embolism in older patients: aretrospective analysis of three large cohorts." (http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20354012). BMJ 340: c1475.doi:10.1136/bmj.c1475 (http://dx.doi.org/10.1136%2Fbmj.c1475). PMID 20354012(//www.ncbi.nlm.nih.gov/pubmed/20354012).
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