Highly Elevated Quantitative D-Dimer Assay Values Increase the Likelihood of Venous Thromboembolism

Abstract

Objectives In patients with suspected venous thromboembolism (VTE), the D-dimer assay is commonly utilized as part of the workup. The assay is primarily used to determine whether to proceed with radiographic imaging. We compared D-dimer levels in patients suspected of having VTE. We hypothesized that higher D-dimer values predict a higher likelihood of subsequent VTE diagnosis.

Methods We conducted a secondary analysis of a multinational, prospective observational study of low- to intermediate-risk adult patients presenting to the emergency department with suspicion of VTE. Demographic and clinical data were collected in a structured manner. Advanced imaging including ultrasound, computed tomography (CT) pulmonary angiography, and ventilation/perfusion scanning was obtained at the discretion of the treating physicians. Imaging was evaluated by board-certified radiologists in real time. D-dimer values' bins were evaluated using a logistic regression model.

Results We evaluated 1,752 patients for suspected deep vein thrombosis (DVT), with 191 (10.4%) DVT positive. We evaluated 1,834 patients for suspected pulmonary embolism (PE), with 108 (5.9%) PE positive. Higher D-dimer values in both groups were associated with higher likelihood of subsequent VTE diagnosis, with D-dimer values > 3,999 ng/mL in both groups having the highest incidence of VTE. More than 50% of those patients were VTE positive.

Conclusions Increasing D-dimer values predict increased likelihood of being found VTE positive in this patient population. Among those in the highest D-dimer category, > 3,999 ng/mL, over half of patients were VTE positive. Further research could determine additional nuance in D-dimer as a tool to work up suspected VTE.

Keywords

venous thrombosis - deep vein thrombosis - pulmonary embolism

Note

Data originally presented at American College of Emergency Physicians (ACEP) Scientific Assembly 2017, Washington DC. Plenary Abstract #12, October 31, 2017. Abstract title: Highly Elevated Quantitative D-Dimer Assay Values Increase the Likelihood of Venous Thromboembolism.

• References

• 1 Stein PD, Hull RD, Patel KC. , et al. D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Ann Intern Med 2004; 140 (08) 589-602
• 2 Kline JA, Nelson RD, Jackson RE, Courtney DM. 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 (02) 144-152
• 3 Oudega R, Moons KG, Hoes AW. Ruling out deep venous thrombosis in primary care. A simple diagnostic algorithm including D-dimer testing. Thromb Haemost 2005; 94 (01) 200-205
• 4 Ilkhanipour K, Wolfson AB, Walker H. , et al. Combining clinical risk with D-dimer testing to rule out deep vein thrombosis. J Emerg Med 2004; 27 (03) 233-239
• 5 Kristoffersen AH, Ajzner E, Rogic D. , et al; joint Working Group on Postanalytical Phase (WG-POST) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) and European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM). Is D-dimer used according to clinical algorithms in the diagnostic work-up of patients with suspicion of venous thromboembolism? A study in six European countries. Thromb Res 2016; 142: 1-7
• 6 Kabrhel C, Van Hylckama Vlieg A, Muzikanski A. , et al. Multicenter evaluation of the YEARS criteria in emergency department patients evaluated for pulmonary embolism. Acad Emerg Med 2018; 25 (09) 987-994
• 7 McLenachan CJ, Chua O, Chan BS, Vecellio E, Chiew AL. Comparison of Wells and YEARS clinical decision rules with D-dimer for low risk pulmonary embolus patients. Intern Med J 2018; doi: 10.1111/imj.14138
• 8 Duriseti RS, Brandeau ML. Cost-effectiveness of strategies for diagnosing pulmonary embolism among emergency department patients presenting with undifferentiated symptoms. Ann Emerg Med 2010; 56 (04) 321-332.e10
• 9 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 (05) 519-524
• 10 Carrier M, Righini M, Djurabi RK. , et al. VIDAS D-dimer in combination with clinical pre-test probability to rule out pulmonary embolism. A systematic review of management outcome studies. Thromb Haemost 2009; 101 (05) 886-892
• 11 Murphy N, Broadhurst DI, Khashan AS, Gilligan O, Kenny LC, O'Donoghue K. Gestation-specific D-dimer reference ranges: a cross-sectional study. BJOG 2015; 122 (03) 395-400
• 12 Righini M, Van Es J, Den Exter PL. , et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA 2014; 311 (11) 1117-1124
• 13 van der Hulle T, Cheung WY, Kooij S. , et al; YEARS study group. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet 2017; 390 (10091): 289-297
• 14 Tick LW, Nijkeuter M, Kramer MH. , et al; Christopher Study Investigators. High D-dimer levels increase the likelihood of pulmonary embolism. J Intern Med 2008; 264 (02) 195-200
• 15 Kohn MA, Klok FA, van Es N. D-dimer interval likelihood ratios for pulmonary embolism. Acad Emerg Med 2017; 24 (07) 832-837
• 16 Shah K, Quaas J, Rolston D. , et al. Magnitude of D-dimer matters for diagnosing pulmonary embolus. Am J Emerg Med 2013; 31 (06) 942-945
• 17 Nata S, Hiromatsu S, Shintani Y, Ohno T, Akashi H, Tanaka H. D-dimer value more than 3.6 μg/ml is highly possible existence deep vein thrombosis. Kurume Med J 2013; 60 (02) 47-51
• 18 Wolf SJ, Hahn SA, Nentwich LM, Raja AS, Silvers SM, Brown MD. ; American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Thromboembolic Disease. Clinical Policy: Critical issues in the evaluation and management of adult patients presenting to the emergency department with suspected acute venous thromboembolic disease. Ann Emerg Med 2018; 71 (05) e59-e109
• 19 Parry BA, Chang AM, Schellong SM. , et al. International, multicenter evaluation of a new D-dimer assay for the exclusion of venous thromboembolism using standard and age-adjusted cut-offs. Thromb Res 2018; 166: 63-70
• 20 Yan Z, Ip IK, Raja AS, Gupta A, Kosowsky JM, Khorasani R. Yield of CT pulmonary angiography in the emergency department when providers override evidence-based clinical decision support. Radiology 2017; 282 (03) 717-725
• 21 Hutchinson BD, Navin P, Marom EM, Truong MT, Bruzzi JF. Overdiagnosis of pulmonary embolism by pulmonary CT angiography. AJR Am J Roentgenol 2015; 205 (02) 271-277
• 22 Markel A, Weich Y, Gaitini D. Doppler ultrasound in the diagnosis of venous thrombosis. Angiology 1995; 46 (01) 65-73
• 23 Hogg KE, Brown MD, Kline JA. Estimating the pretest probability threshold to justify empiric administration of heparin prior to pulmonary vascular imaging for pulmonary embolism. Thromb Res 2006; 118 (05) 547-553
• 24 Stein PD, Fowler SE, Goodman LR. , et al; PIOPED II Investigators. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med 2006; 354 (22) 2317-2327
• 25 Goodacre S, Sampson F, Thomas S, van Beek E, Sutton A. Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis. BMC Med Imaging 2005; 5: 6
• 26 D'Angelo A, D'Alessandro G, Tomassini L, Pittet JL, Dupuy G, Crippa L. Evaluation of a new rapid quantitative D-dimer assay in patients with clinically suspected deep vein thrombosis. Thromb Haemost 1996; 75 (03) 412-416
• 27 Goldin Y, Pasvolsky O, Rogowski O. , et al. The diagnostic yield of D-dimer in relation to time from symptom onset in patients evaluated for venous thromboembolism in the emergency medicine department. J Thromb Thrombolysis 2011; 31 (01) 1-5
• 28 Mirshahi M, Azzarone B, Soria J, Mirshahi F, Soria C. The role of fibroblasts in organization and degradation of a fibrin clot. J Lab Clin Med 1991; 117 (04) 274-281
• 29 Soria J, Soria C, Caen P. A new type of congenital dysfibrinogenaemia with defective fibrin lysis--Dusard syndrome: possible relation to thrombosis. Br J Haematol 1983; 53 (04) 575-586
• 30 Lijnen HR, Soria J, Soria C, Collen D, Caen JP. Dysfibrinogenemia (fibrinogen Dusard) associated with impaired fibrin-enhanced plasminogen activation. Thromb Haemost 1984; 51 (01) 108-109
• 31 Sartori M, Cosmi B, Legnani C. , et al. The Wells rule and D-dimer for the diagnosis of isolated distal deep vein thrombosis. J Thromb Haemost 2012; 10 (11) 2264-2269
• 32 Kearon C, Akl EA, Ornelas J. , et al. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest 2016; 149 (02) 315-352
• 33 Palareti G. Do isolated calf deep vein thrombosis need anticoagulant treatment?. J Thorac Dis 2016; 8 (12) E1691-E1693
• 34 Salvagno GL, Lippi G, Manzato F. , et al. Analytical comparison of AxSYM, HemosIL DD HS and Innovance D-dimer immunoassays with the Vidas D-dimer. Int J Lab Hematol 2009; 31 (04) 475-477