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Semin Respir Crit Care Med 2008; 29(1): 015-024
DOI: 10.1055/s-2008-1047559
© Thieme Medical Publishers

Clinical Probability and D-dimer Testing: How Should We Use Them in Clinical Practice?

C. William Hargett1 , Victor F. Tapson1
  • 1Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina
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Publication History

Publication Date:
26 March 2008 (online)

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ABSTRACT

Venous thromboembolism (VTE) is extraordinarily common and is a major cause of morbidity and mortality. However, accurate and timely diagnosis of VTE is confounded by its kaleidoscopic presentation. Clinical prediction rules (CPRs) and D-dimer testing have both been increasingly employed to clarify the complex decision making required in such cases. Formal clinical pretest probability now serves as the root of algorithms for the diagnosis of DVT and PE. A low pretest probability of VTE plus a negative D dimer can be combined in a bayesian fashion to effectively exclude the diagnosis of VTE. The evidence for this strategy is strongest in younger outpatients with no associated comorbidities, no prior history of VTE, and a short duration of symptoms.

KEYWORDS

Diagnosis - deep vein thrombosis - pulmonary embolism - clinical probability - bayesian prediction - D dimer

REFERENCES

  • 1 Spencer F A, Emery C, Lessard D et al.. The Worcester Venous Thromboembolism study: a population-based study of the clinical epidemiology of venous thromboembolism.  J Gen Intern Med. 2006;  21 722-727
    CrossrefPubMedGoogle Scholar
  • 2 Horlander K T, Mannino D M, Leeper K V. Pulmonary embolism mortality in the United States, 1979-1998: an analysis using multiple-cause mortality data.  Arch Intern Med. 2003;  163 1711-1717
    CrossrefPubMedGoogle Scholar
  • 3 Kollef M H, Zahid M, Eisenberg P R. Predictive value of a rapid semiquantitative D-dimer assay in critically ill patients with suspected venous thromboembolic disease.  Crit Care Med. 2000;  28 414-420
    PubMedGoogle Scholar
  • 4 Lee A Y, Julian J A, Levine M N et al.. Clinical utility of a rapid whole-blood D-dimer assay in patients with cancer who present with suspected acute deep venous thrombosis.  Ann Intern Med. 1999;  131 417-423
    CrossrefPubMedGoogle Scholar
  • 5 Raimondi P, Bongard O, de Moerloose P, Reber G, Waldvogel F, Bounameaux H. D-dimer plasma concentration in various clinical conditions: implication for the use of this test in the diagnostic approach of venous thromboembolism.  Thromb Res. 1993;  69 125-130
    CrossrefPubMedGoogle Scholar
  • 6 Kruskal J B, Commerford P J, Franks J J, Kirsch R E. Fibrin and fibrinogen-related antigens in patients with stable and unstable coronary artery disease.  N Engl J Med. 1987;  317 1361-1365
    PubMedGoogle Scholar
  • 7 Giroud M, Dutrillaux F, Lemesle M et al.. Coagulation abnormalities in lacunar and cortical ischemic stroke are quite different.  Neurol Res. 1998;  20 15-18
    PubMedGoogle Scholar
  • 8 Bellart J, Gilabert R, Fontcuberta J, Borrell M, Miralles R M, Cabero L. Fibrinolysis changes in normal pregnancy.  J Perinat Med. 1997;  25 368-372
    CrossrefPubMedGoogle Scholar
  • 9 Bombeli T, Raddatz-Mueller P, Fehr J. Coagulation activation markers do not correlate with the clinical risk of thrombosis in pregnant women.  Am J Obstet Gynecol. 2001;  184 382-389
    CrossrefPubMedGoogle Scholar
  • 10 Hager K, Platt D. Fibrin degeneration product concentrations (D-dimers) in the course of ageing.  Gerontology. 1995;  41 159-165
    PubMedGoogle Scholar
  • 11 Righini M, Goehring C, Bounameaux H, Perrier A. Effects of age on the performance of common diagnostic tests for pulmonary embolism.  Am J Med. 2000;  109 357-361
    CrossrefPubMedGoogle Scholar
  • 12 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
  • 13 Di Nisio M, Squizzato A, Rutjes A W, Buller H R, Zwinderman A H, Bossuyt P M. Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review.  J Thromb Haemost. 2007;  5 296-304
    CrossrefPubMedGoogle Scholar
  • 14 Freyburger G, Trillaud H, Labrouche S et al.. D-dimer strategy in thrombosis exclusion-a gold standard study in 100 patients suspected of deep venous thrombosis or pulmonary embolism: 8 DD methods compared.  Thromb Haemost. 1998;  79 32-37
    PubMedGoogle Scholar
  • 15 Bounameaux H, Cirafici P, de Moerloose P et al.. Measurement of D-dimer in plasma as diagnostic aid in suspected pulmonary embolism.  Lancet. 1991;  337 196-200
    CrossrefPubMedGoogle Scholar
  • 16 Couturaud F, Kearon C, Bates S M, Ginsberg J S. Decrease in sensitivity of D-dimer for acute venous thromboembolism after starting anticoagulant therapy.  Blood Coagul Fibrinolysis. 2002;  13 241-246
    CrossrefPubMedGoogle Scholar
  • 17 Chapman C S, Akhtar N, Campbell S, Miles K, O'Connor J, Mitchell V E. The use of D-dimer assay by enzyme immunoassay and latex agglutination techniques in the diagnosis of deep vein thrombosis.  Clin Lab Haematol. 1990;  12 37-42
    PubMedGoogle Scholar
  • 18 Galle C, Papazyan J P, Miron M J, Slosman D, Bounameaux H, Perrier A. Prediction of pulmonary embolism extent by clinical findings, D-dimer level and deep vein thrombosis shown by ultrasound.  Thromb Haemost. 2001;  86 1156-1160
    Google Scholar
  • 19 De Monye W, Sanson B J, Mac Gillavry M R et al.. Embolus location affects the sensitivity of a rapid quantitative D-dimer assay in the diagnosis of pulmonary embolism.  Am J Respir Crit Care Med. 2002;  165 345-348
    PubMedGoogle Scholar
  • 20 Constans J, Boutinet C, Salmi L R et al.. Comparison of four clinical prediction scores for the diagnosis of lower limb deep venous thrombosis in outpatients.  Am J Med. 2003;  115 436-440
    CrossrefPubMedGoogle Scholar
  • 21 Subramaniam R M, Snyder B, Heath R, Tawse F, Sleigh J. Diagnosis of lower limb deep venous thrombosis in emergency department patients: performance of Hamilton and modified Wells scores.  Ann Emerg Med. 2006;  48 678-685
    CrossrefPubMedGoogle Scholar
  • 22 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
  • 23 Wells P S, Hirsh J, Anderson D R et al.. Accuracy of clinical assessment of deep-vein thrombosis.  Lancet. 1995;  345 1326-1330
    CrossrefPubMedGoogle Scholar
  • 24 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
  • 25 Tamariz L J, Eng J, Segal J B et al.. Usefulness of clinical prediction rules for the diagnosis of venous thromboembolism: a systematic review.  Am J Med. 2004;  117 676-684
    CrossrefPubMedGoogle Scholar
  • 26 Wells P S, Owen C, Doucette S, Fergusson D, Tran H. Does this patient have deep vein thrombosis?.  JAMA. 2006;  295 199-207
    CrossrefPubMedGoogle Scholar
  • 27 Oudega R, Hoes A W, Moons K G. The Wells rule does not adequately rule out deep venous thrombosis in primary care patients.  Ann Intern Med. 2005;  143 100-107
    CrossrefPubMedGoogle Scholar
  • 28 Penaloza A, Laureys M, Wautrecht J C, Lheureux P, Motte S. Accuracy and safety of pretest probability assessment of deep vein thrombosis by physicians in training using the explicit Wells clinical model.  J Thromb Haemost. 2006;  4 278-281
    CrossrefPubMedGoogle Scholar
  • 29 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
  • 30 Kraaijenhagen R A, Piovella F, Bernardi E et al.. Simplification of the diagnostic management of suspected deep vein thrombosis.  Arch Intern Med. 2002;  162 907-911
    CrossrefPubMedGoogle Scholar
  • 31 Perrier A, Desmarais S, Miron M J et al.. Non-invasive diagnosis of venous thromboembolism in outpatients.  Lancet. 1999;  353 190-195
    Google Scholar
  • 32 Heijboer H, Buller H R, Lensing A W, Turpie A G, 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
  • 33 Keeling D M, Mackie I J, Moody A, Watson H G. The diagnosis of deep vein thrombosis in symptomatic outpatients and the potential for clinical assessment and D-dimer assays to reduce the need for diagnostic imaging.  Br J Haematol. 2004;  124 15-25
    Google Scholar
  • 34 Siragusa S, Anastasio R, Porta C et al.. Deferment of objective assessment of deep vein thrombosis and pulmonary embolism without increased risk of thrombosis: a practical approach based on the pretest clinical model, D-dimer testing, and the use of low-molecular-weight heparins.  Arch Intern Med. 2004;  164 2477-2482
    CrossrefPubMedGoogle Scholar
  • 35 Prandoni P, Lensing A W, Bernardi E, Villalta S, Bagatella P, Girolami A. The diagnostic value of compression ultrasonography in patients with suspected recurrent deep vein thrombosis.  Thromb Haemost. 2002;  88 402-406
    PubMedGoogle Scholar
  • 36 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
  • 37 Rathbun S W, Whitsett T L, Raskob G E. Negative D-dimer result to exclude recurrent deep venous thrombosis: a management trial.  Ann Intern Med. 2004;  141 839-845
    CrossrefPubMedGoogle Scholar
  • 38 The PIOPED Investigators . 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
  • 39 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
  • 40 Wells P S, Anderson D R, Rodger M 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
  • 41 Fattorini A, Crippa L, Vigano'D'Angelo S, Pattarini E, D'Angelo A. Risk of deep vein thrombosis recurrence: high negative predictive value of D-dimer performed during oral anticoagulation.  Thromb Haemost. 2002;  88 162-163
    PubMedGoogle Scholar
  • 42 Palareti G, Legnani C, Cosmi B et al.. Predictive value of D-dimer test for recurrent venous thromboembolism after anticoagulation withdrawal in subjects with a previous idiopathic event and in carriers of congenital thrombophilia.  Circulation. 2003;  108 313-318
    CrossrefPubMedGoogle Scholar
  • 43 Eichinger S, Minar E, Bialonczyk C et al.. D-dimer levels and risk of recurrent venous thromboembolism.  JAMA. 2003;  290 1071-1074
    CrossrefPubMedGoogle Scholar
  • 44 Stein P D, Terrin M L, Hales C A et al.. Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease.  Chest. 1991;  100 598-603
    CrossrefPubMedGoogle Scholar
  • 45 Stein P D, Saltzman H A, Weg J G. Clinical characteristics of patients with acute pulmonary embolism.  Am J Cardiol. 1991;  68 1723-1724
    CrossrefPubMedGoogle Scholar
  • 46 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
  • 47 Miniati M, Pistolesi M, Marini C et al.. Value of perfusion lung scan in the diagnosis of pulmonary embolism: results of the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED).  Am J Respir Crit Care Med. 1996;  154 1387-1393
    PubMedGoogle Scholar
  • 48 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
  • 49 Rosen M P, Sands D Z, Morris J, Drake W, Davis R B. Does a physician's ability to accurately assess the likelihood of pulmonary embolism increase with training?.  Acad Med. 2000;  75 1199-1205
    PubMedGoogle Scholar
  • 50 Sanson B J, Lijmer J G, Mac Gillavry M R, Turkstra F, Prins M H, Buller H R. Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group.  Thromb Haemost. 2000;  83 199-203
    PubMedGoogle Scholar
  • 51 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
  • 52 Runyon M S, Webb W B, Jones A E, Kline J A. Comparison of the unstructured clinician estimate of pretest probability for pulmonary embolism to the Canadian score and the Charlotte rule: a prospective observational study.  Acad Emerg Med. 2005;  12 587-593
    CrossrefPubMedGoogle Scholar
  • 53 Chunilal S D, Eikelboom J W, Attia J et al.. Does this patient have pulmonary embolism?.  JAMA. 2003;  290 2849-2858
    CrossrefPubMedGoogle Scholar
  • 54 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
    Google Scholar
  • 55 Bosson J L, Barro C, Satger B, Carpentier P H, Polack B, Pernod G. Quantitative high D-dimer value is predictive of pulmonary embolism occurrence independently of clinical score in a well-defined low risk factor population.  J Thromb Haemost. 2005;  3 93-99
    CrossrefPubMedGoogle Scholar
  • 56 van Belle A, Buller H R, Huisman M V et al.. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography.  JAMA. 2006;  295 172-179
    CrossrefPubMedGoogle Scholar
  • 57 Kearon C, Ginsberg J S, Douketis J et al.. An evaluation of D-dimer in the diagnosis of pulmonary embolism: a randomized trial.  Ann Intern Med. 2006;  144 812-821
    CrossrefPubMedGoogle Scholar
  • 58 Kruip M J, Slob M J, Schijen J H, van der Heul C, Buller H R. Use of a clinical decision rule in combination with D-dimer concentration in diagnostic workup of patients with suspected pulmonary embolism: a prospective management study.  Arch Intern Med. 2002;  162 1631-1635
    CrossrefPubMedGoogle Scholar
  • 59 Rodger M A, Maser E, Stiell I, Howley H E, Wells P S. The interobserver reliability of pretest probability assessment in patients with suspected pulmonary embolism.  Thromb Res. 2005;  116 101-107
    CrossrefPubMedGoogle Scholar
  • 60 Wolf S J, McCubbin T R, Feldhaus K M, Faragher J P, Adcock D M. Prospective validation of Wells criteria in the evaluation of patients with suspected pulmonary embolism.  Ann Emerg Med. 2004;  44 503-510
    PubMedGoogle Scholar
  • 61 Nordenholz K E, Naviaux N W, Stegelmeier K et al.. Pulmonary embolism risk assessment screening tools: the interrater reliability of their criteria.  Am J Emerg Med. 2007;  25 285-290
    CrossrefPubMedGoogle Scholar
  • 62 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
  • 63 Le Gal G, Righini M, Roy P M et al.. Prediction of pulmonary embolism in the emergency department: the revised Geneva score.  Ann Intern Med. 2006;  144 165-171
    CrossrefPubMedGoogle Scholar
  • 64 Kline J A, Nelson R D, Jackson R E, Courtney D M. Criteria for the safe use of D-dimer testing in emergency department patients with suspected pulmonary embolism: a multicenter US study.  Ann Emerg Med. 2002;  39 144-152
    CrossrefPubMedGoogle Scholar
  • 65 Kline J A, Runyon M S, Webb W B, Jones A E, Mitchell A M. Prospective study of the diagnostic accuracy of the simplify D-dimer assay for pulmonary embolism in emergency department patients.  Chest. 2006;  129 1417-1423
    CrossrefPubMedGoogle Scholar
  • 66 Hyers T M. Venous thromboembolism.  Am J Respir Crit Care Med. 1999;  159 1-14
    PubMedGoogle Scholar
  • 67 Musset D, Parent F, Meyer G et al.. Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study.  Lancet. 2002;  360 1914-1920
    CrossrefPubMedGoogle Scholar
  • 68 Ghanima W, Almaas V, Aballi S et al.. Management of suspected pulmonary embolism (PE) by D-dimer and multi-slice computed tomography in outpatients: an outcome study.  J Thromb Haemost. 2005;  3 1926-1932
    CrossrefPubMedGoogle Scholar
  • 69 Tapson V F, Carroll B A, Davidson B L et al.. The diagnostic approach to acute venous thromboembolism: clinical practice guideline. American Thoracic Society.  Am J Respir Crit Care Med. 1999;  160 1043-1066
    PubMedGoogle Scholar
  • 70 Stein P D, Woodard P K, Weg J G et al.. Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II Investigators.  Radiology. 2007;  242 15-21
    CrossrefPubMedGoogle Scholar
  • 71 Qaseem A, Snow V, Barry P et al.. Current diagnosis of venous thromboembolism in primary care: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians.  Ann Intern Med. 2007;  146 454-458
    PubMedGoogle Scholar
  • 72 Clinical policy: critical issues in the evaluation and management of adult patients presenting with suspected pulmonary embolism.  Ann Emerg Med. 2003;  41 257-270
    PubMedGoogle Scholar
  • 73 British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group . British Thoracic Society guidelines for the management of suspected acute pulmonary embolism.  Thorax. 2003;  58 470-483
    CrossrefPubMedGoogle Scholar
  • 74 Fedullo P F, Tapson V F. Clinical practice: the evaluation of suspected pulmonary embolism.  N Engl J Med. 2003;  349 1247-1256
    CrossrefPubMedGoogle Scholar
  • 75 Nilsson T, Turen J, Billstrom A, Mare K, Carlsson A, Nyman U. Validity of pulmonary cine arteriography for the diagnosis of pulmonary embolism.  Eur Radiol. 1999;  9 276-280
    CrossrefPubMedGoogle Scholar
  • 76 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
  • 77 Hull R D, Raskob G E, Coates G, Panju A A. Clinical validity of a normal perfusion lung scan in patients with suspected pulmonary embolism.  Chest. 1990;  97 23-26
    CrossrefPubMedGoogle Scholar
  • 78 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
  • 79 Perrier A, Roy P M, Sanchez O et al.. Multidetector-row computed tomography in suspected pulmonary embolism.  N Engl J Med. 2005;  352 1760-1768
    CrossrefPubMedGoogle Scholar
  • 80 Perrier A, Roy P M, Aujesky D et al.. Diagnosing pulmonary embolism in outpatients with clinical assessment, D-dimer measurement, venous ultrasound, and helical computed tomography: a multicenter management study.  Am J Med. 2004;  116 291-299
    Google Scholar
  • 81 Stein P D, Fowler S E, Goodman L R et al.. Multidetector computed tomography for acute pulmonary embolism.  N Engl J Med. 2006;  354 2317-2327
    CrossrefPubMedGoogle Scholar
  • 82 Roy P M, Meyer G, Vielle B et al.. Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism.  Ann Intern Med. 2006;  144 157-164
    CrossrefPubMedGoogle Scholar

Victor F TapsonM.D. F.C.C.P. 

Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center

Box 31175, Durham, NC 27710

Email: tapso001@mc.duke.edu