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Semin Vasc Med 2005; 05(4): 340-350
DOI: 10.1055/s-2005-922479
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

The Role of Qualitative D-Dimer Assays, Clinical Probability, and Noninvasive Imaging Tests for the Diagnosis of Deep Vein Thrombosis and Pulmonary Embolism

Philip S. Wells1
  • 1Department of Medicine, Ottawa Hospital and the University of Ottawa, Ottawa, Ontario
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Publication History

Publication Date:
22 November 2005 (online)

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ABSTRACT

Recent advances in the management of patients with suspected venous thromboembolism have both improved diagnostic accuracy as well as made management algorithms safer and more accessible. It is now clear that determination of clinical probability prior to diagnostic testing will improve patient management. D-dimer testing can be employed to decrease the need for imaging tests. Patients at low risk with a negative qualitative D-dimer can avoid imaging tests. Imaging test interpretation benefits from consideration of pretest probability also as this helps clinicians determine when a test may be falsely negative or falsely positive. Diagnostic strategies should include pretest clinical probability, D-dimer assays, and noninvasive imaging tests.

KEYWORDS

Diagnosis - clinical assessment - D-dimer - deep vein thrombosis - pulmonary embolism

REFERENCES

  • 1 Hirsh J, Bates S M. Prognosis in acute pulmonary embolism.  Lancet. 1999;  353 1375-1376
    CrossrefPubMedGoogle Scholar
  • 2 Prandoni P, Lensing AWA, Prins M. Long-term outcomes after deep venous thrombosis of the lower extremities.  Vasc Med. 1998;  3 57-60
    CrossrefPubMedGoogle Scholar
  • 3 Fedullo P F, Auger W R, Channick R N, Kerr K M, Rubin L J. Chronic thromboembolic pulmonary hypertension.  Clin Chest Med. 2001;  22 561-581
    CrossrefPubMedGoogle Scholar
  • 4 Heit J, Silverstein M D, Mohr D N, Petterson T M, O'Fallon W M, Melton III L M. Predictors of survival after deep vein thrombosis and pulmonary embolism.  Arch Intern Med. 1999;  159 445-453
    CrossrefPubMedGoogle Scholar
  • 5 Schluger N, Henschke C, King T et al.. Diagnosis of pulmonary embolism at a large teaching hospital.  J Thorac Imaging. 1994;  9 180-184
    PubMedGoogle Scholar
  • 6 Lensing A W, Prandoni P, Brandjes DPM et al.. Detection of deep-vein thrombosis by real-time B-mode ultrasonography.  N Engl J Med. 1989;  320 342-345
    Google Scholar
  • 7 Cogo A, Lensing AWA, Koopman MMW et al.. Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study.  BMJ. 1998;  316 17-20
    Google Scholar
  • 8 Heijboer H, Buller H R, Lensing AWA, Turpie AGG, Colly L P, ten Cate J W. A comparison of real-time compression ultrasonography with impedance plethysmography for the diagnosis of deep-vein thrombosis in symptomatic outpatients.  N Engl J Med. 1993;  329 1365-1369
    Google Scholar
  • 9 Anand S S, Wells P S, Hunt D, Brill-Edwards P, Cook D, Ginsberg J S. Does this patient have deep vein thrombosis?.  JAMA. 1998;  279 1094-1099
    CrossrefPubMedGoogle Scholar
  • 10 Kearon C, Julian J A, Newman T E, Ginsberg J S. Noninvasive diagnosis of deep vein thrombosis.  Ann Intern Med. 1998;  128 663-677
    Google Scholar
  • 11 Wells P S, Lensing AWA, Davidson B L, Prins M H, Hirsh J. Accuracy of ultrasound for the diagnosis of deep venous thrombosis in asymptomatic patients after orthopedic surgery. A meta-analysis.  Ann Intern Med. 1995;  122 47-53
    PubMedGoogle Scholar
  • 12 Perone N, Bounameaux H, Perrier A. Comparison of four strategies for diagnosing deep vein thrombosis: a cost-effectiveness analysis.  Am J Med. 2001;  110 33-40
    Google Scholar
  • 13 Hillner B E, Philbrick J T, Becker D M. Optimal management of suspected lower-extremity deep vein thrombosis. An evaluation with cost assessment of 24 management strategies.  Arch Intern Med. 1992;  152 165-175
    CrossrefPubMedGoogle Scholar
  • 14 Stevens S M, Elliot C G, Chan K J, Egger M J, Ahmed K M. Withholding anticoagulation after a negative result on duplex ultrasonography for suspected symptomatic deep venous thrombosis.  Ann Intern Med. 2004;  140 985-991
    CrossrefPubMedGoogle Scholar
  • 15 Schellong S M, Schwarz T, Halbritter K et al.. Complete compression ultrasonography of the leg veins as a single test for the diagnosis of deep vein thrombosis.  Thromb Haemost. 2003;  89 228-234
    Google Scholar
  • 16 Elias A, Mallard L, Elias M et al.. A single complete ultrasound investigation of the venous network for the diagnostic management of patients with a clinically suspected first episode of deep venous thrombosis of the lower limbs.  Thromb Haemost. 2003;  89 221-227
    Google Scholar
  • 17 Stein P D, Athanasoulis C, Alavi A et al.. Complications and validity of pulmonary angiography in acute pulmonary embolism.  Circulation. 1992;  85 462-468
    PubMedGoogle Scholar
  • 18 The PIOPED Investigators . The value of the ventilation/perfusion scan in acute pulmonary embolism: Results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED).  JAMA. 1990;  263 2753-2759
    Google Scholar
  • 19 Henry J W, Relyea B, Stein P D. Continuing risk of thromboemboli among patients with normal pulmonary angiograms.  Chest. 1995;  107 1375-1378
    CrossrefPubMedGoogle Scholar
  • 20 Hull R D, Hirsh J, Carter C J et al.. Pulmonary angiography, ventilation lung scanning, and venography for clinically suspected pulmonary embolism with abnormal perfusion lung scan.  Ann Intern Med. 1983;  98 891-899
    CrossrefPubMedGoogle Scholar
  • 21 Rathbun S W, Raskob G, Whitsett T L. Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review.  Ann Intern Med. 2000;  132 227-232
    PubMedGoogle Scholar
  • 22 Mullins M D, Becker D M, Hagspiel K D, Philbrick J T. The role of spiral volumetric computed tomography in the diagnosis of pulmonary embolism.  Arch Intern Med. 2000;  160 293-298
    CrossrefPubMedGoogle Scholar
  • 23 Mayo J R, Remy-Jardin M, Muller N L et al.. Pulmonary embolism: prospective comparison of spiral CT with ventilation-perfusion scintigraphy.  Radiology. 1997;  205 447-452
    PubMedGoogle Scholar
  • 24 Shah A A, Davis S D, Gamsu G, Intriere L. Parenchymal and pleural findings in patients with and patients without acute pulmonary embolism detected at spiral CT.  Radiology. 1999;  211 147-153
    PubMedGoogle Scholar
  • 25 Wells P S, Anderson D R, Rodger M et al.. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis.  N Engl J Med. 2003;  349 1227-1235
    Google Scholar
  • 26 Kearon C, Ginsberg J S, Douketis J D et al.. Management of suspected deep venous thrombosis in outpatients by using clinical assessment and D-dimer testing.  Ann Intern Med. 2001;  135 108-111
    PubMedGoogle Scholar
  • 27 Anderson D R, Wells P S, Stiell I et al.. Management of patients with suspected deep vein thrombosis in the emergency department: combining use of a clinical diagnosis model with D-dimer testing.  J Emerg Med. 2000;  19 225-230
    CrossrefPubMedGoogle Scholar
  • 28 Bates S M, Kearon C, Crowther M A et al.. A diagnostic strategy involving a quantitative latex D-dimer assay reliably excludes deep venous thrombosis.  Ann Intern Med. 2003;  138 787-794
    CrossrefPubMedGoogle Scholar
  • 29 Wells P S, Anderson D R, Bormanis J et al.. Value of assessment of pretest probability of deep-vein thrombosis in clinical management.  Lancet. 1997;  350 1795-1798
    Google Scholar
  • 30 Schutgens R E, Ackermark P, Haas F J et al.. Combination of a normal D-dimer concentration and a non-high pretest clinical probability score is a safe strategy to exclude deep venous thrombosis.  Circulation. 2003;  107 593-597
    CrossrefPubMedGoogle Scholar
  • 31 Shields G P, Turnipseed S, Panacek E A, Melnikoff N, Gosselin R, White R H. Validation of the Canadian clinical probability model for acute venous thrombosis.  Acad Emerg Med. 2002;  9 561-566
    CrossrefPubMedGoogle Scholar
  • 32 Wells P S, Ginsberg J S, Anderson D R et al.. Use of a clinical model for safe management of patients with suspected pulmonary embolism.  Ann Intern Med. 1998;  129 997-1005
    Google Scholar
  • 33 Sanson B J, Lijmer J G, MacGillavry MRM, Turkstra F, Prins M H, Buller H R. Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism.  Thromb Haemost. 2000;  83 199-203
    PubMedGoogle Scholar
  • 34 Miniati M, Prediletto R, Formichi B et al.. Accuracy of clinical assessment in the diagnosis of pulmonary embolism.  Am J Respir Crit Care Med. 1999;  159 864-871
    CrossrefPubMedGoogle Scholar
  • 35 Wicki J, Perneger T V, Junod A F, Bounameaux H, Perrier A. Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score.  Arch Intern Med. 2001;  161 92-97
    CrossrefPubMedGoogle Scholar
  • 36 Chagnon I, Bounameaux H, Aujesky D et al.. Comparison of two clinical prediction rules and implicit assessment among patients with suspected pulmonary embolism.  Am J Med. 2002;  113 269-275
    CrossrefPubMedGoogle Scholar
  • 37 Kovacs M J, MacKinnon K M, Anderson D R et al.. A comparison of three rapid D-dimer methods for the diagnosis of venous thromboembolism.  Br J Haematol. 2001;  115 140-144
    CrossrefPubMedGoogle Scholar
  • 38 Heim S W, Schectman J M, Siadaty M S, Philbrick J T. D-dimer testing for deep venous thrombosis: a metaanalysis.  Clin Chem. 2004;  50 1136-1147
    PubMedGoogle Scholar
  • 39 Perzanowski C, Dellweg D, Eiger G. Limited use of the SimpliRED assay in confirming pulmonary embolism.  Thromb Haemost. 2004;  91 633-635
    PubMedGoogle Scholar
  • 40 Meyer G, Fischer A M, Collignon M A et al.. Diagnostic value of two rapid and individual D-dimer assays in patients with clinically suspected pulmonary embolism: comparison with microplate enzyme-linked immunosorbent assay.  Blood Coagul Fibrinolysis. 1998;  9 603-608
    PubMedGoogle Scholar
  • 41 de Monye W, Huisman M V, Pattynama PMT. Observer dependency of the Simplired D-dimer assay in 81 consecutive patients with suspected pulmonary embolism.  Thromb Res. 1999;  96 293-298
    CrossrefPubMedGoogle Scholar
  • 42 Turkstra F, van Beek E J, Buller H R. Observer and biological variation of a rapid whole blood d-dimer test.  Thromb Haemost. 1998;  79 91-93
    PubMedGoogle Scholar
  • 43 Philbrick J T, Heim S W. The D-dimer test for deep venous thrombosis: gold standards and bias in negative predictive value.  Clin Chem. 2003;  49 570-574
    PubMedGoogle Scholar
  • 44 Stein P D, Hull R D, Patel K C et al.. D-Dimer for the exclusion of acute venous thrombosis and pulmonary embolism. A systematic review.  Ann Intern Med. 2004;  140 589-602
    PubMedGoogle Scholar
  • 45 Kraaijenhagen R A, Lijmer J G, Bossuyt PMM, Prins M H, Heisterkamp S H, Buller H R. The accuracy of D-dimer in the diagnosis of venous thromboembolism: a meta-analysis. In: Kraaijenhagen RA Etiology, Diagnosis and Treatment of Venous Thromboembolism. Amsterdam, The Netherlands; 2000: 159-183
    Google Scholar
  • 46 Bauld D L, Kovacs M J. Dalteparin in emergency patients to prevent admission prior to investigation for venous thromboembolism.  Am J Emerg Med. 1999;  17 11-14
    CrossrefPubMedGoogle Scholar
  • 47 Anderson D R, Kovacs M J, Kovacs G et al.. Combined use of clinical assessment and D-dimer to improve the management of patients presenting to the emergency department with suspected deep-vein thrombosis (the EDITED Study).  J Thromb Haemost. 2003;  1 645-651
    Google Scholar
  • 48 Heijboer H, Jongbloets L M, Buller H R, Lensing A W, ten Cate J W. Clinical utility of real-time compression ultrasonography for diagnostic management of patients with recurrent venous thrombosis.  Acta Radiol. 1992;  33 297-300
    CrossrefPubMedGoogle Scholar
  • 49 Hull R D, Raskob G E, Coates G, Panju A A. Clinical validity of a normal perfusion lung scan on patients with suspected pulmonary embolism.  Chest. 1990;  97 23-26
    CrossrefPubMedGoogle Scholar
  • 50 van Beek E J, Kuyer PMM, Schenk B E, Brandjes DPM, ten Cate J W, Buller H R. A normal perfusion lung scan in patients with clinically suspected pulmonary embolism: frequency and clinical validity.  Chest. 1995;  108 170-173
    CrossrefPubMedGoogle Scholar
  • 51 Kipper M S, Moser K M, Kortman K E, Ashburn W L. Longterm follow-up of patients with suspected pulmonary embolism and a normal lung scan. Perfusion scans in embolic suspects.  Chest. 1982;  82 411-415
    PubMedGoogle Scholar
  • 52 Gosselin M V, Rubin G D, Leung A N, Huang J, Rizk N W. Unsuspected pulmonary embolism: prospective detection on routine helical CT scans.  Radiology. 1998;  208 209-215
    PubMedGoogle Scholar
  • 53 Wells P S, Anderson D R, Rodger M A et al.. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: Increasing the models utility with the SimpliRED D-dimer.  Thromb Haemost. 2000;  83 416-420
    Article in Thieme ConnectPubMedGoogle Scholar
  • 54 Worsley D F, Alavi A. Comprehensive analysis of the results of the PIOPED Study. Prospective Investigation of Pulmonary Embolism Diagnosis Study.  J Nucl Med. 1995;  36 2380-2387
    PubMedGoogle Scholar
  • 55 Cohen J. Statistical power analysis for the behavioural sciences. 2nd ed. Hillsdale, NJ; Lawrence Erlbaum Assoc. 1988
    Google Scholar
  • 56 Bayes T. An essay towards solving a problem in the doctrine of chances.  Philos Trans R Soc Lon. 1763;  53 370-418
    PubMedGoogle Scholar
  • 57 Wells P S, Anderson D R, Rodger M A 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
    Google Scholar
  • 58 Berghout A, Oudkerk M, Hicks S G, Teng T H, Pillay M, Buller H R. Active implementation of a consenus strategy improves diagnosis and management in suspected pulmonary embolism.  QJM. 2000;  93 335-340
    CrossrefPubMedGoogle Scholar
  • 59 Goldstein N M, Kollef M H, Ward S, Gage B F. The impact of the introduction of a rapid D-dimer assay on the diagnostic evaluation of suspected pulmonary embolism.  Arch Intern Med. 2001;  161 567-571
    CrossrefPubMedGoogle Scholar

 Dr.
Philip Wells

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Ottawa, Ontario, Canada, K1Y 4E9