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ANNALS OF EMERGENCY MEDICINE OCTOBER 2011
Systematic Review SnapshotTAKE-HOME MESSAGE
There is inadequate evidence to support the use of D-dimer to exclude acute
aortic dissection.Mount Sinai School of Medicine, New York, NY
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METHODS
DATA SOURCESMEDLINE and EMBASE weresearched through 2009; referencelists were hand searched.Searches were limited to publica-tions in English.
STUDY SELECTIONOnly studies that reported aorticdissection occurring within 2weeks of symptom onset and di-agnosed by advanced imaging orautopsy were included. A controlgroup was required for inclusion;case reports and case series wereexcluded.
DATA EXTRACTION ANDSYNTHESISTwo reviewers independently ex-tracted data necessary to com-plete a 2�2 table; disagreementswere resolved by consensus.Study quality was graded with theQuality Assessment of DiagnosticAccuracy Studies (QUADAS) in-strument.1 Data were combinedacross all studies to estimate anoverall sensitivity and specificitywith a random-effects model; sta-tistical heterogeneity was re-ported as I2.
Volume , . : October
Can a Negative D-dimer Result Rule OutAcute Aortic Dissection?EBEM CommentatorsMichael D. Brown, MD, MScDivision of Emergency MedicineMichigan State University College of Human Medicine, Grand Rapids, MI
David H. Newman, MDDepartment of Emergency Medicine
Results
Six cohort studies and 1 case-controlstudy met the inclusion criteria. Al-though 4 different types of D-dimer as-says were used, a standard test thresh-old of greater than 500 ng/mL defined apositive D-dimer result. Each of the in-cluded studies met from 7 to 10 of the14 QUADAS criteria.1 Based on com-bining the results of 298 patients withaortic dissection and 436 without aor-tic dissection, the pooled estimate forsensitivity�0.97 (95% CI 0.94 to 0.99;I2�0%) and specificity�0.56 (95% CI0.51 to 0.60; I2� 82%).
Commentary
Although classic presentations such assharp, tearing chest pain radiating tothe back or a history of connective tis-sue disorder raise the suspicion foracute aortic dissection, there are nosigns or symptoms that decrease thepretest probability sufficiently to ex-clude the diagnosis2; therefore, currentguidelines3 recommend advanced im-aging when aortic dissection is sus-pected. Given the cost and potentialharms associated with computed tomo-graphic pulmonary angiography andthe difficulty of obtaining transesopha-
geal echocardiography in many emer- sency department (ED) settings, an ac-urate biomarker screening test woulde welcomed by emergency medicinelinicians.
he goal of this systematic review waso assess the usefulness of D-dimer toiagnose acute aortic dissection. The
nvestigators performed a comprehen-ive search and assessed the quality ofhe individual studies with a validatednstrument (QUADAS).1 However, therst item of the QUADAS tool asks,Was the spectrum of patients repre-entative of patients who will receivehe test in practice?” and the develop-rs of QUADAS specifically state thattudies that recruit a group of healthyontrols and a group known to havehe target disorder should be coded as ano” on this item.1 The authors of thisystematic review rated all 7 studies asositive for this item, yet closer inspec-ion of the individual studies revealedhat only the registry study4 prospec-ively enrolled ED patients suspected ofaving acute aortic dissection. Most ofhe other studies compared D-dimer re-ults in patients with known aortic dis-ections with those of either healthyolunteers or patients known to havether conditions. For example, one ofhe included studies reporting 100%
ensitivity for D-dimer enrolled exactlyAnnals of Emergency Medicine 375
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Systematic Review Snapshot
16 patients known to have aortic dis-section, 16 with acute myocardial in-farction, 16 with pulmonary embolism,and 16 determined to have noncardiacchest pain.5 It is obvious that this typeof “cohort” is not representative of anunselected ED population presentingwith chest pain. When there is not di-agnostic uncertainty among subjectsenrolled in a diagnostic test study, esti-mates for sensitivity and specificity areoften inflated.
For emergency medicine clinicians,the registry data reported by Suzukiet al4 provide the most valid esti-mates for D-dimer sensitivity andspecificity; however, the relativelysmall sample size (N�220) resultedin imprecise estimates, with a lowerlimit of the 95% confidence interval(CI) of 0.90 for sensitivity and 0.38for specificity. A conservative esti-mate based on these results indi-cates that the negative likelihood ra-tio for D-dimer is approximately 0.2and the positive likelihood ratio is
1.5. If these approximations are val-376 Annals of Emergency Medicine
idated in a larger prospective study,a positive D-dimer result would haveno value in clinical decisionmaking, buta negative D-dimer result may decreasethe probability of aortic dissection toa moderate degree. However, to ruleout aortic dissection with a negativeD-dimer result, the pretest probabilitywould have to be very low. Unfortu-nately, unlike pulmonary embolism oracute myocardial infarction, there areno validated clinical prediction rules toaid clinicians with establishing a pretestprobability of aortic dissection.
1. Whiting P, Rutjes A, Reitsma J, et al. Thedevelopment of QUADAS: a tool for thequality assessment of studies ofdiagnostic accuracy included insystematic reviews. BMC Med ResMethodol. 2003;3:25.
2. Bushnell J, Brown J. Clinical assessmentfor acute thoracic aortic dissection. AnnEmerg Med. 2005;46:90-92.
3. American College of CardiologyFoundation, American Heart AssociationTask Force on Practice Guidelines,American Association for ThoracicSurgery, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM
guidelines for the diagnosis and Emanagement of patients with thoracicaortic disease. J Am Coll Cardiol. 2010;55:e27-129.
. Suzuki T, Distante A, Zizza A, et al.Diagnosis of acute aortic dissection byD-dimer: the International Registry ofAcute Aortic Dissection Substudy onBiomarkers (IRAD-Bio) experience.Circulation. 2009;119:2702-2707.
. Eggebrecht H, Naber CK, Bruch C, et al.Value of plasma fibrin D-dimers fordetection of acute aortic dissection. J AmColl Cardiol. 2004;44:804-809.
his is a clinical synopsis, a regular fea-ure of the Annals’ Systematic Reviewnapshot (SRS) series. The source forhis systematic review snapshot is: Shi-ony A, Filion KB, Mottillo S, et al.eta-analysis of usefulness of D-dimer
o diagnose acute aortic dissection. Am Jardiol. 2011;107:1227-1234.
ystematic Review Author Contactvi Shimony, MDivisions of Cardiology andEpidemiology and Lady DavisInstitute for Medical Research
ewish General Hospital/McGillUniversity
ontreal, Quebec, Canada
-mail: [email protected]Volume , . : October
