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The Importance of Clinical Probability Assessment in Interpreting a Normal d-Dimer in Patients With Suspected Pulmonary Embolism

*From the Department of Vascular Medicine (Drs. Gibson, Sohne, Gerdes, and Buller), Academical Medical Center, Amsterdam, the Netherlands; and the Department of General Internal Medicine (Dr. Nijkeuter), Leiden University Medical Center, Leiden, the Netherlands.

Correspondence to: Nadine Gibson, PhD, Department of Vascular Medicine, Academical Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; e-mail: n.s.gibson{at}amc.uva.nl

Background:The d-dimer test is widely applied in the diagnostic workup of patients with suspected pulmonary embolism (PE). The objective of this study was to investigate how often the d-dimer test fails when clinical probability is not taken into account.

Methods:We used data collected in 1,722 consecutive patients with clinically suspected PE to analyze the 3-month venous thromboembolism (VTE) rate in all patients with a normal d-dimer concentration and separately for patients who have a normal d-dimer concentration with an unlikely or likely clinical probability for PE, as assessed by the Wells clinical decision rule.

Results:The 3-month VTE rate in all patients with a normal d-dimer concentration (n = 563) was 2.3% (95% confidence interval [CI], 1.4 to 3.9%). In the patients with an unlikely probability of PE (n = 477), VTE was confirmed in 1.1% of the patients with a normal d-dimer concentration (95% CI, 0.4 to 2.4%). In those patients with a likely clinical probability of PE (n = 86), VTE was confirmed in 9.3% of the patients with a normal d-dimer concentration (95% CI, 4.8 to 17.3%). The difference in VTE incidence between patients with unlikely and likely clinical probabilities of PE was significant (p < 0.001).

Conclusions:Our findings indicate that it is of utmost importance to first examine the patient and assess the clinical probability, after which the d-dimer concentration can be taken into account, in order to prevent physicians from being influenced by a normal d-dimer test result when they evaluate the clinical probability of PE. Patients with a likely clinical probability should undergo further testing, regardless of the d-dimer test outcome.

Key Words: deep venous thrombosis • pulmonary embolism • thrombosis

Abbreviations: CDR, clinical decision rule • CI, confidence interval • DVT, deep venous thrombosis • IQR, interquartile range • LMWH, low-molecular-weight heparin • PE, pulmonary embolism • VTE, venous thromboembolism