Download PDF
Semin Vasc Med 2005; 05(4): 351-364
DOI: 10.1055/s-2005-922480
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Screening for Deep Vein Thrombosis and Pulmonary Embolism in Outpatients with Suspected DVT or PE by the Sequential Use of Clinical Score: A Sensitive Quantitative D-Dimer Test and Noninvasive Diagnostic Tools

Jan Jacques Michiels1 , 5 , Alain Gadisseur1 , Marc van der Planken2 , Wilfried Schroyens1 , Marianne De Maeseneer3 , Jan T. Hermsen4 , Paul H. Trienekens4 , Henk Hoogsteden6 , Peter M.T Pattynama7
  • 1Hemostasis and Thrombosis Research, Department of Hematology, University Hospital Antwerp, Antwerp, Belgium
  • 2Hemostasis Laboratory Department of Clinical Biology, University Hospital Antwerp, Antwerp, Belgium
  • 3Vascular Laboratory, Department of Vascular Surgery, University Hospital Antwerp, Antwerp, Belgium
  • 4Medical Diagnostic Center Rijnmond, Rotterdam, The Netherlands
  • 5Goodheart Institute, Hematology, Hemostasis & Thrombosis Science Center, Rotterdam, The Netherlands
  • 6Department of Pulmonary Diseases, Erasmus Medical Center, Rotterdam, The Netherlands
  • 7Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands
Further Information

Publication History

Publication Date:
22 November 2005 (online)

    Permissions and Reprints

ABSTRACT

The requirement for a safe diagnostic strategy should be based on an overall posttest incidence of venous thromboembolism (VTE) of less than 1% during 3-month follow-up. The negative predictive value (NPV) during 3 months of follow-up is 98.1 to 99% after a normal venogram, 97 to 98% after a normal compression ultrasonography (CUS), and > 99% after serial CUS testing. Serial CUS testing is safe but 100 CUS must be repeated to find one or two CUS positive for deep vein thrombosis (DVT), which is not cost-effective and indicates the need to improve the diagnostic workup of DVT by the use of clinical score assessment and D-dimer testing. The NPV varies from 97.6 to 99.4% for low clinical score followed by a negative SimpiRED test, indicating the need for a first CUS. The NPV is 98.4 to 99.3% for a normal rapid enzyme-linked immunosorbent assay (ELISA) VIDAS D-dimer test result (< 500 ng/mL) irrespective of clinical score. The NPV is more than 99% for a negative CUS followed by either a negative SimpiRED test or an ELISA VIDAS test result of < 1000 ng/mL without the need to repeat a second CUS within 1 week. The sequential use of a sensitive, rapid ELISA D-dimer and clinical score assessment will safely reduce the need for CUS testing by 40 to 60%. Large prospective outcome studies demonstrate that with one negative examination with complete duplex color ultrasonography (CCUS) of the proximal and distal veins of the affected leg with suspected DVT, it is safe to withhold anticoagulant treatment, with a negative predictive value of 99.5%. This may indicates that CCUS is equal to serial CUS or the combined use of clinical score, D-dimer testing, and CUS. Pulmonary angiography is the gold standard for segmental pulmonary embolism (PE) but not for subsegmental PE. A normal perfusion lung scan and a normal rapid ELISA VIDAS D-dimer test safely excludes PE. Helical spiral computed tomography (CT) detects all clinically relevant PE and a large number of alternative diagnoses in symptomatic patients with suspected PE and can replace both the ventilation perfusion scan and pulmonary angiography to safely rule in PE and to rule out PE with an NPV of > 99%. The combination of clinical assessment, a rapid ELISA VIDAS D-dimer, followed by CUS will reduce the need for helical spiral CT by 40 to 50%.

KEYWORDS

Deep vein thrombosis - D-dimer assay - compression ultrasonography - clinical score - pulmonary embolism - venous thromboembolism - ventilation perfusion scan - spiral CT

REFERENCES

  • 1 Michiels J J, Oortwijn W J, Naaborg R. Exclusion and diagnosis of deep vein thrombosis by a rapid ELISA D-dimer test, compression ultrasonography, and a simple clinical model.  Clin Appl Thromb Hemost. 1999;  5 171-180
    PubMedGoogle Scholar
  • 2 Michiels J J, Freyburger G, van der Graaf F, Janssen M, Oortwijn W, van Beek EJR. Strategies for the safe and effective exclusion and diagnosis of deep vein thrombosis by the sequential use of clinical score, D-dimer testing and compression ultrasonography.  Sem Thromb Hemost. 2000;  26 657-667
    PubMedGoogle Scholar
  • 3 Hull R, Hirsh J, Sackett D L et al.. Clinical validity of a negative venogram in patients with clinically suspected venous thrombosis.  Circulation. 1981;  64 622-625
    CrossrefPubMedGoogle Scholar
  • 4 Pedersen L M, Lerche A, Jorgensen M, Urhammer S, Steenberg P, Jensen R. Follow-up study of patients with clinically suspected deep vein thrombosis and a normal venogram.  J Intern Med. 1993;  234 457-460
    PubMedGoogle Scholar
  • 5 Cogo A, Lensing AWA, Prandoni P, Hirsch J. Distribution of thrombosis in patients with symptomatic deep vein thrombosis.  Arch Intern Med. 1993;  153 2777-2780
    Google Scholar
  • 6 Cogo A, Lensing A W, Koopman M M 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
  • 7 Birdwell B G, Raskob G E, Whitsett T L et al.. The clinical validity of normal compression ultrasonography in outpatients suspected of having deep venous thrombosis.  Ann Intern Med. 1998;  128 1-7
    CrossrefPubMedGoogle Scholar
  • 8 Kearon C, Julian J A, Math M, Newman T E, Ginsberg J S. Non-invasive diagnosis of deep vein thrombosis.  Ann Intern Med. 1998;  128 663-677
    Google Scholar
  • 9 Wells P, Hirsh J, Anderson D R et al.. Accuracy of clinical assessment of deep-vein thrombosis.  Lancet. 1995;  345 1326-1330
    CrossrefPubMedGoogle Scholar
  • 10 Wells P, Anderson D R, Bormanis J et al.. Value of assessment of pre-test probability of deep-vein thrombosis in clinical management.  Lancet. 1997;  350 1795-1798
    Google Scholar
  • 11 Michiels J J, Schroyens W, De Maeseneer M, Kasbergen A A, Oudega R. The rehabilitation of clinical assessment in the diagnosis of deep vein thrombosis.  Sem Vasc Med. 2002;  1 1-5
    PubMedGoogle Scholar
  • 12 Miron M J, Perrier A, Boumameaux H. Clinical assessment of suspected deep vein thrombosis: comparison between a score and empirical assessment.  J Intern Med. 2000;  247 249-254
    CrossrefPubMedGoogle Scholar
  • 13 Kraaijenhagen R A, Piovelli F, Bernardi E et al.. Simplification of the diagnostic management of suspected deep vein thrombosis.  Arch Intern Med. 2002;  162 907-911
    CrossrefPubMedGoogle Scholar
  • 14 Tick L W, Ton E, van Voorthuizen Th et al.. Practical diagnostic management of patients with clinically suspected deep vein thrombosis by clinical probability test, compression ultrasonography and D-dimer test.  Am J Med. 2002;  113 630-635
    Google Scholar
  • 15 Cornuz J, Ghali W A, Hayoz D, Stoianov R, Depairon M, Yersin B. Clinical prediction of deep venous thrombosis using two risk assessment methods in combination with rapid quantitative D-dimer testing.  Am J Med. 2002;  112 198-203
    CrossrefPubMedGoogle Scholar
  • 16 Constans J, Nelzy M L, Salmi L R et al.. Clinical prediction of lower limb deep vein thrombosis in symptomatic hospitalized patients.  Thromb Haemost. 2001;  86 985-990
    PubMedGoogle Scholar
  • 17 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
  • 18 Wells P, Brill-Edwards P, Stevens P et al.. A novel and rapid whole-blood assay for D-dimer in patients with clinically suspected deep vein thrombosis.  Circulation. 1995;  91 2184-2187
    PubMedGoogle Scholar
  • 19 Blättler W, Martinez I, Blättler I K. Diagnosis of deep vein thrombosis and alternative diseases in symptomatic outpatients.  Eur J Intern Med. 2004;  15 305-311
    PubMedGoogle Scholar
  • 20 Bates S M, Kearon C, Crowther M et al.. A diagnostic strategy involving a quantitative latex-D-dimer assay reliable excludes deep vein thrombosis.  Ann Intern Med. 2003;  138 787-794
    CrossrefPubMedGoogle Scholar
  • 21 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
  • 22 Kearon C, Ginsberg J S, Douketis J et al.. Management of suspected deep vein thrombosis in outpatients by using clinical assessment and D-dimer testing.  Ann Intern Med. 2001;  135 108-111
    PubMedGoogle Scholar
  • 23 Freyburger G, Trillaud H, Labrouche S et al.. D-dimer strategy in thrombosis exclusion. A gold standard study in 100 patients suspected of deep vein thrombosis or pulmonary embolism: 8 DD methods compared.  Thromb Haemost. 1998;  79 31-37
    PubMedGoogle Scholar
  • 24 Van Der Graaf F, van den Borne H, van der Kolk M et al.. Exclusion of deep vein thrombosis with D-dimer testing.  Thromb Haemost. 2000;  83 191-198
    PubMedGoogle Scholar
  • 25 Perrier A, Desmarais S, Miron M J et al.. Non-invasive diagnosis of venous thrombo-embolism in outpatients.  Lancet. 1999;  353 190-195
    Google Scholar
  • 26 Michiels J J, Kasbergen HAA, Trienekens P H. Evidence for safe exclusion of deep vein thrombosis (DVT) by the rapid ELISA VIDAS D-dimer test at cut-off levels of 500 and 1000 ng/ml in 1046 consecutive outpatients with suspected DVT.  Blood. 2004;  301a , (abstract 1059)
    PubMedGoogle Scholar
  • 27 Schutgens REG, Ackermark P, Haas FJLM 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
  • 28 Elias A, Mallard L, Elias M et al.. A single complete ultrasound investigation of the venous network for diagnostic management of patients with a clinically suspected first episode of deep vein thrombosis of the lower limbs.  Thromb Haemost. 2003;  89 221-227
    Google Scholar
  • 29 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
  • 30 Stevens S M, Elliott G, Chan K J, Egger M J, Ahmed K M. Withholding anticoagulation after a negative result on duplex ultrasonography for suspected symptomatic deep vein thrombosis.  Ann Intern Med. 2004;  140 985-991
    CrossrefPubMedGoogle Scholar
  • 31 The PIOPED Investigators . Value of the ventilation/perfusion scan in acute pulmonary embolism.  JAMA. 1990;  263 2753-2759
    Google Scholar
  • 32 Oudkerk M, van Beek EJ, van Putten WL, Buller HR. Cost-effectiveness analysis of various strategies in the diagnostic management of pulmonary embolism.  Arch Intern Med. 1993;  153 947-954
    CrossrefPubMedGoogle Scholar
  • 33 Henry J W, Relyea B, Stein P D. Continuing risk of thromboemboli among patients with normal pulmonary angiograms.  Chest. 1995;  107 1735-1738
    PubMedGoogle Scholar
  • 34 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 Inter Med. 1983;  98 891-899
    CrossrefPubMedGoogle Scholar
  • 35 Diffin D C, Leyendecker J R, Johnson S P, Zucker R J, Grebe P J. Effect of anatomic distribution of pulmonary emboli on inter-observer agreement in the interpretation of pulmonary angiography.  AJR Am J Roentgenol. 1998;  171 1085-1089
    CrossrefPubMedGoogle Scholar
  • 36 Michiels J J, Perrier A, Bounameaux H. Should a normal D-dimer rule out angiographic pulmonary embolism or unfavourable outcome in patients left untreated?.  Thromb Haemost. 2001;  85 753-754
    PubMedGoogle Scholar
  • 37 Michiels J J, Schroyens W, De Backer W, Van Der Planken M, Hoogsteden H, Pattynama PMT. Non-invasive exclusion and diagnosis of pulmonary embolism by sequential use of the rapid ELISA D-dimer assay, clinical score and spiral CT.  Int Angiol. 2003;  22 1-14
    PubMedGoogle Scholar
  • 38 Hoellerich V L, Wigton R S. Diagnosing pulmonary embolism using clinical findings.  Arch Intern Med. 1986;  146 1699-1704
    CrossrefPubMedGoogle Scholar
  • 39 Celi A, Palla A, Petruzzelli S et al.. Prospective study of a standardized questionnaire to improve clinical estimate of pulmonary embolism.  Chest. 1989;  95 332-337
    PubMedGoogle Scholar
  • 40 Wells PS, Ginsberg JS, Anderson DR 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
  • 41 Sanson B J, Lijmer J G, MacGilevry M R, Turkstra F, Prins M H, Büller 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
  • 42 Wells PS, Anderson DR, 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 a D-dimer.  Ann Intern Med. 2001;  135 98-107
    Google Scholar
  • 43 Wicki J, Perneger T V, Junod A F, Bounameaux H, Perrier A. Assessing clinical probability of pulmonary embolism in the emergency ward.  Arch Intern Med. 2001;  161 92-97
    CrossrefPubMedGoogle Scholar
  • 44 Bounameaux H, Slosman D, de Moerloose P, Reber G. Diagnostic value of plasma D-dimer in suspected pulmonary embolism.  Lancet. 1988;  2 628-629
    PubMedGoogle Scholar
  • 45 Bounameaux H, Schneider P A, Slosman D, de Moerloose P, Reber G. Plasma D-dimer in suspected pulmonary embolism: a comparison with pulmonary angiography and ventilation-perfusion scintigraphy.  Blood Coagul Fibrinolysis. 1990;  1 577-579
    PubMedGoogle Scholar
  • 46 Bounameaux H, Cirefici P, de Moerloose Ph. Measurement of D-dimer in plasma as diagnostic aid in suspected pulmonary embolism.  Lancet. 1991;  337 196-200
    CrossrefPubMedGoogle Scholar
  • 47 Rowbotham B J, Egerton-Vermont J, Whitaker A N et al.. Plasma cross linked fibrin degradation products in pulmonary embolism.  Thorax. 1990;  45 684-687
    PubMedGoogle Scholar
  • 48 Goldhaber S Z, Simons G R, Elliott G et al.. Quantitative plasma D-dimer levels among patients undergoing pulmonary angiography for suspected pulmonary embolism.  JAMA. 1993;  270 2819-2822
    CrossrefPubMedGoogle Scholar
  • 49 Van Beek EJR, van den Ende B, Berkmans R J et al.. A comparative analysis of D-dimer assays in patients with clinically suspected pulmonary embolism.  Thromb Haemost. 1993;  70 408-413
    PubMedGoogle Scholar
  • 50 Van Beek EJR, Schenk E, Michel B C et al.. The role of plasma D-dimer concentration in the exclusion of pulmonary embolism.  Br J Haematol. 1996;  92 725-732
    CrossrefPubMedGoogle Scholar
  • 51 Perrier A, Bounameaux H, Morabia A et al.. Diagnosis of pulmonary embolism by a decision analysis-based strategy including clinical probability, D-dimer levels, and ultrasonography: a management study.  Arch Intern Med. 1996;  156 531-536
    CrossrefPubMedGoogle Scholar
  • 52 Perrier A, Desmarais S, Goehring C et al.. D-dimer testing for suspected pulmonary embolism in outpatients.  Am J Respir Crit Care Med. 1997;  156 492-496
    PubMedGoogle Scholar
  • 53 Opinions regarding the diagnosis and management of venous thromboembolic disease. ACCP Consensus Committee on Pulmonary Embolism. American College of Chest Physicians.  Chest. 1998;  113 499-504
    PubMedGoogle Scholar
  • 54 De Moerloose P, Desmarais S, Bounameaux H et al.. Contribution of a new rapid, individual and quantitative automated Vidas D-dimer ELISA to exclude pulmonary embolism.  Thromb Haemost. 1996;  75 11-13
    PubMedGoogle Scholar
  • 55 Kruip M J, Slob M J, Schijen FHEM, van der Heul C, Büller H R. Use of a clinical decision rule in combination with D-dimer concentration in diagnostic workup of patients with suspected pulmonary embolism.  Arch Intern Med. 2002;  162 1631-1635
    CrossrefPubMedGoogle Scholar
  • 56 Ferretti G R, Bosson J-L, Buffaz P D et al.. Acute pulmonary embolism: role of helical CT in 164 patients with intermediate probability at ventilation-perfusion scintigraphy and normal results at duplex of the legs.  Radiology. 1997;  205 453-458
    PubMedGoogle Scholar
  • 57 Ost D, Rozenshstein A, Saffran L, Snider A. The negative predictive value of spiral computed tomography for the diagnosis of pulmonary embolism in patients with non-diagnostic ventilation-perfusion scans.  Am J Med. 2001;  110 16-21
    CrossrefPubMedGoogle Scholar
  • 58 Lomis NNT, Yoon H C, Miller F J. Clinical outcomes of patients after a negative spiral CT pulmonary angiogram in the evaluation of acute pulmonary embolism.  J Vasc Interv Radiol. 1999;  10 707-712
    PubMedGoogle Scholar
  • 59 Garg K, Sieler H, Welsh C H, Johnston R, Russ P. Clinical validity of helical CT being interpreted as negative for pulmonary embolism. Implications for patient treatment.  AJR Am J Roentgenol. 1999;  172 1627-1631
    PubMedGoogle Scholar
  • 60 Goodman L R, Lipchik R J, Kuzo R S, McAuliffe T L, O'Brien D J. Subsequent pulmonary embolism: risk after a negative helical CT pulmonary angiogram. Prospective comparison with scintigraphy.  Radiology. 2000;  215 535-542
    PubMedGoogle Scholar
  • 61 Göttsäter A, Berg A, Centegard J, Frennby B, Nirhov N, Nyman U. Clinically suspected pulmonary embolism: is it safe to withhold anticoagulation after a negative spiral CT?.  Eur Radiol. 2001;  11 65-72
    CrossrefPubMedGoogle Scholar
  • 62 Tillie-Leblond I, Mastora I, Radenne F et al.. Risk of pulmonary embolism after a negative spiral CT angiogram in patients with pulmonary disease: 1 year clinical follow-up study.  Radiology. 2002;  223 461-467
    PubMedGoogle Scholar
  • 63 Van Strijen MJL, de Monyé W, Schiereck J et al.. Helical CT as the primary diagnostic test in suspected pulmonary embolism: prospective ANTELOPEW multicenter trial in 512 patients.  Ann Intern Med. 2003;  138 307-314
    PubMedGoogle Scholar
  • 64 Musset D, Parent F, Meyer G et al.. Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicenter outcome study.  Lancet. 2002;  360 1914-1920
    CrossrefPubMedGoogle Scholar
  • 65 Perrier A, Roy P-M, Aujesky D et al.. Bounameaux. Diagnosing pulmonary embolism in outpatients with clinical assessment, D-Dimer measurement, venous ultrasound, and helical computed tomography: a multicenter study.  Am J Med. 2004;  116 291-299
    Google Scholar
  • 66 Verschuren Fr, Hainaut P, Thys Fr et al.. ELISA D-dimer measurement for the clinical suspicion of pulmonary embolism in the emergency department: one-year observational study of the safety profile and physician'S prescription.  Acta Clin Belg. 2003;  58 233-240
    PubMedGoogle Scholar

Jan Jacques MichielsM.D. Ph.D. 

Goodheart Institute & Foundation, Hematology Hemostasis Thrombosis Science Center

Erasmus Tower, Veenmos 13, 3069 AT Rotterdam, The Netherlands