Clinical usefulness of D-dimer testing in cancer patients with suspected pulmonary embolism

Marc Righini; Grégoire Le Gal; Sylvain De Lucia; Pierre-Marie Roy; Guy Meyer; Drahomir Aujesky; Henri Bounameaux; Arnaud Perrier

doi:10.1160/TH05-12-0791

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(04): 715-719
DOI: 10.1160/TH05-12-0791

Cellular Proteolysis and Oncology

Schattauer GmbH

Clinical usefulness of D-dimer testing in cancer patients with suspected pulmonary embolism

Marc Righini

¹Division of Angiology and Hemostasis, Geneva, Switzerland

,

Grégoire Le Gal

³Department of Internal Medicine and Chest Diseases, EA 3878 (GETBO), Brest University Hospital, Brest, France

,

Sylvain De Lucia

²Division of General Internal Medicine, Department of Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland

,

Pierre-Marie Roy

⁵Emergency Department, Angers University Hospital, Angers, France

,

Guy Meyer

⁴Service of Pneumology, Hôpital Européen Georges Pompidou, Paris, France

,

Drahomir Aujesky

⁶Department of Internal Medicine, University of Lausanne, Switzerland

,

Henri Bounameaux

¹Division of Angiology and Hemostasis, Geneva, Switzerland

,

Arnaud Perrier

²Division of General Internal Medicine, Department of Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland

› Author Affiliations

Abstract

Summary

Limited data are available about the diagnostic value of D-dimer testing in cancer patients with clinically suspected pulmonary embolism (PE).Therefore, we evaluated i) the safety and clinical usefulness of an ELISA D-dimer test to rule out PE in cancer patients compared with non-cancer patients and ii) whether adopting a higher D-dimer cut-off value might increase the usefulness of D-dimer in cancer patients. We analysed data from two outcome studies which enrolled 1,721 consecutive patients presenting in the emergency department with clinically suspected PE. Presence of an active malignancy was abstracted from the database. All patients underwent a sequential diagnostic work-up including an ELISA D-dimer test and a 3-month followup. Sensitivity and predictive value (NPV) were 100% in both cancer and non-cancer patients. PE was ruled out by a negative D-dimer test in 494/1,554 (32%) patients without cancer, and in 18/164 (11%) patients witha malignancy. At cut-off values varying from 500 to 900 µg/l, the sensitivity was unchanged (100%, 95% CI: 93% to 100%) and the specificity increased from 16% (95% CI:11% to 24%) to 30% (95% CI:22% to 39%).The 3-month thromboembolic risk was 0% (95 % CI: 0% to 18%) in cancer patients witha negative D-dimer test. ELISA D-dimer appears safe to rule out pulmonary embolism in cancer patients but it is negative in only one of ten patients at the usual cut-off value. Increasing the cut-off value of D-dimer in cancer patients might increase the test’s clinical usefulness.

Keywords

Cancer - cut-off - D-dimer - diagnosis - pulmonary embolism

Full Text

References

References
1 Trousseau A. Phlegmasia alba dolens. Clinique Médicale de l’Hôtel-Dieu de Paris 1865; 03: 654-712.
2 Agnelli G. Venous thromboembolism and cancer: a two-way clinical association. Thromb Haemost 1997; 78: 117-20.
3 Stein PD. et al. D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Ann Intern Med 2004; 140: 589-602.
4 Brown MD. et al. The accuracy of the enzyme-linked immunosorbent assay D-dimer test in the diagnosis of pulmonary embolism: a meta-analysis. Ann Emerg Med 2002; 40: 133-44.
5 Brown MD. et al. Turbidimetric D-dimer test in the diagnosis of pulmonary embolism: a meta-analysis. Clin Chem 2003; 49: 1846-53.
6 Chunilal SD. et al. The sensitivity and specificity of a red blood cell agglutination D-dimer assay for venous thromboembolism when performed on venous blood. Arch Intern Med 2002; 162: 217-20.
7 Wells PS. et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003; 349: 1227-35.
8 Perrier A. et al. Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet 1999; 353: 190-5.
9 Perrier A. 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: 291-9.
10 Miron MJ. et al. Contribution of non-invasive evaluation to the diagnosis of pulmonary embolism in hospitalized patients. Eur Respir J 1999; 13: 1365-70.
11 Raimondi P. et al. 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: 125-30.
12 Chabloz P. et al. TAFI antigen and D-dimer levels during normal pregnancy and at delivery. Br J Haematol 2001; 115: 150-2.
13 Epiney M. et al. D-dimer levels during delivery and the postpartum. J Thromb Haemost 2005; 03: 268-71.
14 Righini M. et al. Clinical usefulness of D-dimer depending on clinical probability and cut-off value in outpatients with suspected pulmonary embolism. Arch Intern Med 2004; 164: 2483-7.
15 Righini M. et al. Effects of age on the performance of common diagnostic tests for pulmonary embolism. Am J Med 2000; 109: 357-61.
16 Linkins LA. et al. Use of different D-dimer levels to exclude venous thromboembolism depending on clinical pretest probability. J Thromb Haemost 2004; 02: 1256-60.
17 Righini M. et al. Should the D-dimer cut-off value be increased in elderly patients suspected of pulmonary embolism?. Thromb Haemost 2001; 85: 744.
18 en Wolde M, et al. The clinical usefulness of D-dimer testing in cancer patients with suspected deep venous thrombosis. Arch Intern Med 2002; 162: 1880-4.
19 Lee AY. 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: 417-23.
20 Di Nisio M. et al. D-Dimer test in cancer patients with suspected acute pulmonary embolism. J Thromb Haemost 2005; 03: 1239-42.
21 Perrier A. et al. Multidetector-row computed tomography in suspected pulmonary embolism. N Engl J Med 2005; 352: 1760-8.
22 Wicki J. et al. Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score. Arch Intern Med 2001; 161: 92-7.
23 Chagnon I. et al. Comparison of two clinical prediction rules and implicit assessment among patients with suspected pulmonary embolism. Am J Med 2002; 113: 269-75.
24 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: 2753-9.
25 Gart JJ, Nam J. Approximate interval estimation of the ratio of binomial parameters: a review and corrections for skewness. Biometrics 1988; 44: 323-38.
26 Santner TS, Snell MK. Small sample confidence intervals for p1-p2 and p1/p2 in 2X2 contingency tables. J Am Stat Assoc 1980; 75: 386-94.