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SimpliRed D-dimer does not rule out suspected pulmonary embolus

Three Part Question

In [a patient suspected of having an acute pulmonary embolus] is [a negative SimpliRed d-dimer assay] able to [rule out PE]?

Clinical Scenario

A 40 year old man presents with acute suspected pulmonary embolus (PE). You wonder whether a negative SimpliRed d-dimer assay is sufficient to rule out the diagnosis of PE.

Search Strategy

Medline 1966-07/00 using the OVID interface.
[{(Exp pulmonary embolism or pulmonary OR {( AND (exp embolism or embolism$.mp)} OR (exp thromboembolism or] AND (Simplired$ OR exp fibrin fibrinogen degredation products or d-dimer$.mp)]

Search Outcome

172 papers found of which 162 were irrelevant and 6 of insufficient quality for inclusion. The remaining 4 papers are shown in the table.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Ginsberg JS, et al
Canada & Netherlands
Patients referred to TE consultant, suspected of acute PEProspective cohortSensitivity94% (CI 70-99%)Reference Standard (RS) not applied to all patients Large CI's, therefore need verification in a more powerful study
Prevalence of PE in trial patients19%
Specificity 66% (53-77%)
Positive predictive value38%
Negative predictive value98%
Ginsberg JS, et al
Over 18's clinically suspected PE, referred to Thromboembolism (TE) consultantProspective CohortIn Low PTP negative Likelyhood ratio (LR)0.27Follow-up not same in all groups For subgroup analysis only LR-ve given, no sensitivity or specificity No further identification of patient's presenting problem No sample size calculation No CI's given
In Low PTP specificity75%
In Low Pre Test Probability (PTP) sensitivity79%
Overall Likelihood ratio for negative result0.22
Overall Likelihood ratio for positive result2.7
Overall Specificity68.4%
Overall sensitivity 84.8%
de Groot MR, et al
In-patients and outpatients suspected of PEProspective management studyFalse –ve d-dimer results10% of normal SimpliRED results had PEIncorporation bias Reference standard (RS) not universally applied No sample size calculation No CI's given
Farrell S, et al
Consecutive patients referred from ED for ?DVT and PEProspective clinical trialSensitivity68% (CI 54-83%)Reference standard (RS) not applied to all patients Wide CI's
Prevalence of PE in trial patients32.8%
SpecificityNPV 83% (CI 75-91%)
Likelihood ratio for negative result0.42 (CI 0.26- 0.66)


The "gold standard" investigation for the diagnosis of PE is pulmonary angiography. However, the universal application of this investigation in all patients, in any clinical trial for the investigation of PE, is unethical; the morbidity and mortality associated with this investigation are unacceptably high. Therefore most research is conducted using decision making analysis tools; this would be acceptable if all study patients are subject to the same diagnostic tests. If this does not happen, the validity of the results can be questioned. In the above trials, where the CI's are given, the width of the interval is large; this could be remedied with a larger more powerful trial. As they stand, the CI's are too wide.

Clinical Bottom Line

SimpliRed doesn't have the required sensitivity to be used to rule out PE in an ED setting.


  1. Ginsberg JS, Wells PS, Brill-Edwards P, et al. Application of a novel and rapid whole blood assay for D-dimer in patients with clinically suspected pulmonary embolism. Thromb Haemost 1995;73(1):35-8.
  2. Ginsberg JS, Wells PS, Kearon C, et al. Sensitivity and specificity of a rapid whole-blood assay for D-dimer in the diagnosis of pulmonary embolism. Ann Intern Med 1998;129(12):1006-1011.
  3. de Groot MR, van Marwijk Kooy M, Powels JG, et al. The use of a rapid D-dimer blood test in the diagnostic work-up for pulmonary embolism: a management study. Thromb Haemost 1999;82(6):1588-92.
  4. Farrell S, Hayes T, Shaw M. A negative SimpliRED D-dimer assay result does not exclude the diagnosis of deep vein thrombosis or pulmonary embolus in emergency department patients. Ann Emerg Med 2000;35(2):121-125.