title: Potential impact of adjusting the threshold of the quantitative D-dimer based on pretest probability of acute pulmonary embolism.
abstract: OBJECTIVE
  The utility of D-dimer testing for suspected pulmonary embolism (PE) can be limited by test specificity. The authors tested if the threshold of the quantitative D-dimer can be varied according to pretest probability (PTP) of PE to increase specificity while maintaining a negative predictive value (NPV) of >99%.
  
  
  METHODS
  This was a prospective, observational multicenter study of emergency department (ED) patients in the United States. Eligible patients had a diagnostic study ordered to evaluate possible PE. PTP was determined by the clinician's unstructured estimate and the Wells score. Five different D-dimer assays were used. D-dimer test performance was measured using 1) standard thresholds and 2) variable threshold values: twice (for low PTP patients), equal (intermediate PTP patients), or half (high PTP patients) of standard threshold. Venous thromboembolism (VTE) within 45 days required positive imaging plus decision to treat.
  
  
  RESULTS
  The authors enrolled 7,940 patients tested for PE, and clinicians ordered a quantitative D-dimer for 4,357 (55%) patients who had PTPs distributed as follows: low (74%), moderate (21%), or high (4%). At standard cutoffs, across all PTP strata, quantitative D-dimer testing had a test sensitivity of 94% (95% confidence interval [CI] = 91% to 97%), specificity of 58% (95% CI = 56% to 60%), and NPV of 99.5% (95% CI = 99.1% to 99.7%). If variable cutoffs had been used the overall sensitivity would have been 88% (95% CI = 83% to 92%), specificity 75% (95% CI = 74% to 76%), and NPV 99.1% (95% CI = 98.7% to 99.4%).
  
  
  CONCLUSIONS
  This large multicenter observational sample demonstrates that emergency medicine clinicians currently order a D-dimer in the majority of patients tested for PE, including a large proportion with intermediate PTP and high PTP. Varying the D-dimer's cutoff according to PTP can increase specificity with no measurable decrease in NPV.
authors.affiliation: Department of Emergency Services, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kabrhel
authors.forename: D
authors.initials: D
authors.lastname: Mark Courtney
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Camargo
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Moore
authors.forename: Peter B
authors.initials: PB
authors.lastname: Richman
authors.forename: Michael C
authors.initials: MC
authors.lastname: Plewa
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Nordenholtz
authors.forename: Howard A
authors.initials: HA
authors.lastname: Smithline
authors.forename: Daren M
authors.initials: DM
authors.lastname: Beam
authors.forename: Michael D
authors.initials: MD
authors.lastname: Brown
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kline
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D000792:Angiography; D000933:Antifibrinolytic Agents; D004636:Emergency Service, Hospital; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000175:diagnosis* / Q000453:epidemiology; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000933:Antifibrinolytic Agents; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D