Potential impact of adjusting the threshold of the quantitative D-dimer based on pretest probability of acute pulmonary embolism.
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.
Kabrhel
Christopher
C
Department of Emergency Services, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Mark Courtney
D
D
Camargo
Carlos A
CA
Moore
Christopher L
CL
Richman
Peter B
PB
Plewa
Michael C
MC
Nordenholtz
Kristen E
KE
Smithline
Howard A
HA
Beam
Daren M
DM
Brown
Michael D
MD
Kline
Jeffrey A
JA
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
D000933:Antifibrinolytic Agents; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D