Serum D-Dimer is a Sensitive Test for the Detection of Acute Aortic Dissection: A Pooled Meta-Analysis

  • Keith A. Marill
    Reprint Address: Keith A. Marill, md, Department of Emergency Medicine, Massachusetts General Hospital, Zero Emerson Place, Suite 3B, Boston, MA 02114
    Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
    Search for articles by this author


      Acute aortic dissection is a rare but devastating condition with high mortality. Unfortunately, there is no sensitive screening indicator of disease in common use. The objective of this study was to assess the sensitivity and utility of the serum D-dimer as a test for acute aortic dissection. A pooled analysis was performed of all original research studies testing the sensitivity of serum D-dimer for acute aortic dissection. A search of MEDLINE, EMBASE, and the Cochrane Register using the terms “aortic dissection” and “d-dimer” was made of all English language publications. All original reports of consecutively enrolled patients with acute aortic dissection and a measured serum D-dimer were included. Case reports were excluded. A value of 0.5 microgram per milliliter was defined as the threshold for a positive D-dimer. The primary outcome was the pooled sensitivity of the D-dimer test for acute aortic dissection. There were 21 original reports of patients with acute aortic dissection and D-dimer measurements. Eleven studies were included and a total of 349 acute aortic dissection patients were described. The sensitivity of the D-dimer test was 327/349, 94% (95% confidence interval 91–96), and the point estimate was essentially unchanged in a sensitivity analysis, 183/192, 95% (95% confidence interval 91–98). Specificity ranged from 40% to 100%. Serum D-dimer is sensitive for acute aortic dissection and potentially represents a useful test for patients who present with a low likelihood of this disease.


      To read this article in full you will need to make a payment


      Subscribe to Journal of Emergency Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Meszaros I.
        • Morocz J.
        • Szlavi J.
        • et al.
        Epidemiology and clinicopathology of aortic dissection.
        Chest. 2000; 117: 1271-1278
        • Klompas M.
        Does this patient have an acute thoracic aortic dissection?.
        JAMA. 2002; 287: 2262-2272
        • Sullivan P.R.
        • Wolfson A.B.
        • Leckey R.D.
        • Burke J.L.
        Diagnosis of acute thoracic aortic dissection in the emergency department.
        Am J Emerg Med. 2000; 18: 46-50
        • von Kodolitsch Y.
        • Nienaber C.A.
        • Dieckmann C.
        • et al.
        Chest radiography for the diagnosis of acute aortic syndrome.
        Am J Med. 2004; 116: 73-77
        • Moriyama Y.
        • Toyohira H.
        • Koga M.
        • et al.
        Influence of aortic dissection on the clotting-fibrinolysis system and platelet function.
        Int J Angiol. 1998; 7: 65-67
        • Weber T.
        • Hogler S.
        • Auer J.
        • et al.
        D-dimer in acute aortic dissection.
        Chest. 2003; 123: 1375-1378
        • Eggebrecht H.
        • Naber C.K.
        • Bruch C.
        • et al.
        Value of plasma fibrin D-dimers for detection of acute aortic dissection.
        J Am Coll Cardiol. 2004; 44: 804-809
        • Perez A.
        • Abbet P.
        • Drescher M.J.
        D-dimers in the emergency department evaluation of aortic dissection.
        Acad Emerg Med. 2004; 11: 397-400
        • Hazui H.
        • Fukumoto H.
        • Negoro N.
        • et al.
        Simple and useful tests for discriminating between acute aortic dissection of the ascending aorta and acute myocardial infarction in the emergency setting.
        Circ J. 2005; 69: 677-682
        • Akutsu K.
        • Sato N.
        • Yamamoto T.
        • et al.
        A rapid bedside D-dimer assay (cardiac D-dimer) for screening of clinically suspected acute aortic dissection.
        Circ J. 2005; 69: 397-403
        • Ohlmann P.
        • Faure A.
        • Petit H.
        • et al.
        Diagnostic and prognostic value of circulating D-dimers in patients with acute aortic dissection.
        Crit Care Med. 2006; 34: 1358-1364
        • Weber T.
        • Rammer M.
        • Auer J.
        • Maurer E.
        • Aspock G.
        • Eber B.
        Plasma concentrations of D-dimer predict mortality in acute type A aortic dissection.
        Heart. 2006; 92: 836-837
        • Hazui H.
        • Nishimoto M.
        • Hoshiga M.
        • et al.
        Young adult patients with short dissection length and thrombosed false lumen without ulcer-like projections are liable to have false-negative results of D-dimer testing for acute aortic dissection based on a study of 113 cases.
        Circ J. 2006; 70: 1598-1601
        • Monaco M.
        • Di Tommaso L.
        • Stassano P.
        • et al.
        Impact of blood coagulation and fibrinolytic system changes on early and mid term clinical outcome in patients undergoing stent endografting surgery.
        Interact Cardiovasc Thorac Surg. 2006; 5: 724-728
        • Sbarouni E.
        • Georgiadou P.
        • Marathias A.
        • Geroulanos S.
        • Kremastinos D.T.
        D-dimer and BNP levels in acute aortic dissection.
        Int J Cardiol. 2007; 122: 170-172
        • Bossuyt P.M.
        • Reitsma J.B.
        • Bruns D.E.
        • et al.
        Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative.
        BMJ. 2003; 326: 41-44
        • Bossuyt P.M.
        • Reitsma J.B.
        • Bruns D.E.
        • et al.
        The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration.
        Clin Chem. 2003; 49: 7-18
        • Stroup D.F.
        • Berlin J.A.
        • Morton S.C.
        • et al.
        Meta-analysis of observational studies in epidemiology.
        JAMA. 2000; 283: 2008-2012
        • Whiting P.
        • Rutjes A.W.
        • Reitsma J.B.
        • Bossuyt P.M.
        • Kleijnen J.
        The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews.
        BMC Med Res Methodol. 2003; 3: 25
        • Hagan P.G.
        • Nienaber C.A.
        • Isselbacher E.M.
        • et al.
        The International Registry of Acute Aortic Dissection (IRAD): new insights into an old disease.
        JAMA. 2000; 283: 897-903
        • Zamora J.
        • Muriel A.
        • Abraira V.
        Meta-DiSc for Windows: a software package for the meta-analysis of diagnostic tests. XI Cochrane Colloquium. Barcelona, 2003.
        (Accessed May 28, 2006)
        • Deeks J.J.
        Systematic reviews of evaluations of diagnostic and screening tests.
        in: Egger M. Davy Smith G. Altman D.G. Systematic reviews in health care: meta-analysis in context, 2nd edn. BMJ Books, London, UK2001: 248-282
        • Deeks J.J.
        Systematic reviews of evaluations of diagnostic and screening tests.
        BMJ. 2001; 323: 157-162
        • Berlin J.A.
        • Laird N.M.
        • Sacks H.S.
        • Chalmers T.C.
        A comparison of statistical methods for combining event rates from clinical trials.
        Stat Med. 1989; 8: 141-151
        • Ingelfinger J.A.
        • Mosteller F.
        • Thibodeau L.A.
        • Ware J.H.
        Using meta-analysis for research synthesis: pooling data from several studies.
        in: Biostatistics in clinical medicine. 3rd edn. McGraw-Hill, New York1994: 340
        • D'Aloia A.
        • Faggiano P.
        • Brentana L.
        • Dei Cas L.
        D-dimer levels in a case of type B aortic dissection.
        J Cardiovasc Med (Hagerstown). 2006; 7: 216-218
        • Donovan E.M.
        • Seidel G.K.
        • Cohen A.
        Painless aortic dissection presenting as high paraplegia: a case report.
        Arch Phys Med Rehabil. 2000; 81: 1436-1438
        • Lay C.-S.
        • Yu C.-J.
        • Tyan Y.-S.
        Abdominal aortic dissection with acute mesenteric ischemia in a patient with Marfan syndrome.
        J Chin Med Assoc. 2006; 69: 326-329
        • Kiernan T.J.
        Aortic dissection and elevated D-dimers—an important clinical link.
        Int J Cardiol. 2007; 114: E77-E78
        • Flanagan L.
        • Bancroft R.
        • Rittoo D.
        The value of d-dimer in the diagnosis of acute aortic dissection.
        Int J Cardiol. 2007; 118: e70-e71
        • Iyano K.
        • Kawada T.
        • Aiba M.
        • Takaba T.
        Correlation of hemostatic markers and morphology of the residual false lumen in chronic aortic dissection.
        Ann Thorac Cardiovasc Surg. 2004; 10: 106-112
        • Shimazaki T.
        • Ishimaru S.
        • Kawaguchi S.
        • Yokoi Y.
        • Watanabe Y.
        Blood coagulation and fibrinolytic response after endovascular stent grafting of thoracic aorta.
        J Vasc Surg. 2006; 37: 1213-1218
        • Gando S.
        • Kameue T.
        • Sawamura A.
        • Hayakawa M.
        • Hoshino H.
        • Kubota N.
        An alternative pathway for fibrinolysis is activated in patients who have undergone cardiopulmonary bypass surgery and major abdominal surgery.
        Thromb Res. 2007; 120: 87-93
        • Song F.
        • Khan K.S.
        • Dinnes J.
        • Sutton A.J.
        Asymmetric funnel plots and publication bias in meta-analyses of diagnostic accuracy.
        Int J Epidemiol. 2002; 31: 88-95
        • Iannelli G.
        • Piscione F.
        • DiTommaso L.
        • Monaco M.
        • Chiariello M.
        • Spampinato N.
        Thoracic aortic emergencies: impact of endovascular surgery.
        Ann Thorac Surg. 2004; 77: 591-596
        • Suzuki T.
        • Katoh H.
        • Tsuchio Y.
        • et al.
        Diagnostic implications of elevated levels of smooth-muscle myosin heavy-chain protein in acute aortic dissection.
        Ann Intern Med. 2000; 133: 537-541
        • Shinohara T.
        • Suzuki K.
        • Okada M.
        • et al.
        Soluble elastin fragments in serum are elevated in acute aortic dissection.
        Arterioscler Thromb Vasc Biol. 2003; 23: 1839-1844
        • Wells P.S.
        • Anderson D.R.
        • Rodger M.
        • et al.
        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. 2001; 135: 98-107
        • von Kodolitsch Y.
        • Schwart A.G.
        • Nienaber C.A.
        Clinical prediction of acute aortic dissection.
        Arch Intern Med. 2000; 160: 2977-2982
        • Kabrhel C.
        • Matts C.
        • McNamara M.
        • Katz J.
        • Ptak T.
        A highly sensitive ELISA D-dimer increases testing but not diagnosis of pulmonary embolism.
        Acad Emerg Med. 2006; 13: 519-542
        • Wiegand J.
        • Koller M.
        • Bingisser R.
        Does a negative D-dimer test rule out aortic dissection?.
        Swiss Med Wkly. 2007; 137: 462
        • Lijmer J.G.
        • Mol B.W.
        • Heisterkamp S.
        • et al.
        Empirical evidence of design-related bias in studies of diagnostic tests.
        JAMA. 1999; 282: 1061-1066
        • Stein P.D.
        • Hull R.D.
        • Patel K.C.
        • et al.
        D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism.
        Ann Intern Med. 2004; 140: 589-602
        • Brown M.D.
        • Lau J.
        • Nelson R.D.
        • Kline J.A.
        Turbidimetric D-dimer test in the diagnosis of pulmonary embolism: a metaanalysis.
        Clin Chem. 2003; 49: 1846-1853