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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 embolism.mp) OR {(pulmonary.mp) AND (exp embolism or embolism$.mp)} OR (exp thromboembolism or thromboembolic.mp)] AND (Simplired$ 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 1995 Canada & Netherlands	Patients referred to TE consultant, suspected of acute PE	Prospective cohort	Sensitivity	94% (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 patients	19%
			Specificity	66% (53-77%)
			Positive predictive value	38%
			Negative predictive value	98%
Ginsberg JS, et al 1998 Canada	Over 18's clinically suspected PE, referred to Thromboembolism (TE) consultant	Prospective Cohort	In Low PTP negative Likelyhood ratio (LR)	0.27	Follow-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 specificity	75%
			In Low Pre Test Probability (PTP) sensitivity	79%
			Overall Likelihood ratio for negative result	0.22
			Overall Likelihood ratio for positive result	2.7
			Overall Specificity	68.4%
			Overall sensitivity	84.8%
de Groot MR, et al 1999 Netherlands	In-patients and outpatients suspected of PE	Prospective management study	False –ve d-dimer results	10% of normal SimpliRED results had PE	Incorporation bias Reference standard (RS) not universally applied No sample size calculation No CI's given
			Sensitivity	90%
Farrell S, et al 2000 USA	Consecutive patients referred from ED for ?DVT and PE	Prospective clinical trial	Sensitivity	68% (CI 54-83%)	Reference standard (RS) not applied to all patients Wide CI's
			Prevalence of PE in trial patients	32.8%
			Specificity	NPV 83% (CI 75-91%)
			Likelihood ratio for negative result	0.42 (CI 0.26- 0.66)

Comment(s)

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.

References

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.