An evaluation of D-dimer in the diagnosis of pulmonary embolism: a randomized trial.
BACKGROUND
It may be safe to omit additional diagnostic testing in selected patients with suspected pulmonary embolism (PE) who have a negative D-dimer test, but this approach has never been evaluated in a randomized, controlled trial.


OBJECTIVE
To determine if additional diagnostic testing can be safely withheld in patients with suspected PE who have negative erythrocyte agglutination D-dimer test results.


METHODS
Randomized comparisons in 2 subgroups of a prospective multicenter study.


METHODS
7 university hospitals.


METHODS
1126 outpatients or inpatients with suspected PE; of these, 456 patients with negative erythrocyte agglutination D-dimer test results were randomly assigned to the intervention groups. Patients were classified into 2 clinical probability groups: those with a low clinical probability of PE (low-probability group) and those with a moderate or high clinical probability of PE, a nondiagnostic ventilation-perfusion lung scan, and no evidence of proximal deep venous thrombosis on bilateral ultrasonography (moderate- or high-probability group).


METHODS
The experimental intervention for both probability groups was no further diagnostic testing for PE. The control intervention for the low-probability group was a ventilation-perfusion lung scan followed by ultrasonography of the proximal deep veins of the legs on the same day. If the lung scan was nondiagnostic, ultrasonography of the legs was repeated 7 and 14 days later. The control intervention for the moderate- or high-probability group was ultrasonography of the proximal deep veins of the legs after 7 and 14 days. In the control and experimental groups, anticoagulation was withheld or withdrawn if PE was not diagnosed.


METHODS
Symptomatic venous thromboembolism (VTE) during 6 months of follow-up.


RESULTS
Prevalence of VTE was 15.2% in the 1126 enrolled patients. In the low-probability group, VTE occurred during follow-up in 0 of 182 patients who had no additional diagnostic testing and in 1 of 185 patients who had additional testing (difference, -0.5 percentage point [95% CI, -3.0 to 1.6 percentage points]). In the moderate- or high-probability group, VTE occurred during follow-up in 1 of 41 patients who had no additional diagnostic testing and in 0 of 41 patients who had additional testing (difference, 2.4 percentage points [CI, -6.4 to 12.6 percentage points]).


CONCLUSIONS
The authors could not enroll 2000 patients as originally planned; 3 randomly assigned patients did not receive the allocated intervention, and 7 received inadequate follow-up. Personnel who performed follow-up evaluations were not blinded to the results of diagnostic testing at enrollment or to allocation group assignments.


CONCLUSIONS
In patients with a low probability of PE who have negative D-dimer results, additional diagnostic testing can be withheld without increasing the frequency of VTE during follow-up. Low clinical probability and negative D-dimer results occur in 50% of outpatients and in 20% of inpatients with suspected PE.
Kearon
Clive
C
McMaster University and the Henderson Research Centre, Hamilton, Ontario, Canada. kearonc@mcmaster.ca
Ginsberg
Jeffrey S
JS
Douketis
James
J
Turpie
Alexander G
AG
Bates
Shannon M
SM
Lee
Agnes Y
AY
Crowther
Mark A
MA
Weitz
Jeffrey I
JI
Brill-Edwards
Patrick
P
Wells
Philip
P
Anderson
David R
DR
Kovacs
Michael J
MJ
Linkins
Lori-Ann
LA
Julian
Jim A
JA
Bonilla
Laura R
LR
Gent
Michael
M
D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D005500:Follow-Up Studies; D006801:Humans; D007297:Inpatients; D017063:Outcome Assessment, Health Care; D010045:Outpatients; D011336:Probability; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000175:diagnosis*; D020246:Venous Thrombosis / Q000175:diagnosis*
D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D