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Three Part Question

In [suspected PE] is [bedside clinical examination and simpliRED D-dimer sufficiently sensitive] at [ruling out PE]?

Clinical Scenario

A 34 year old woman presents with a 2 day history of pleuritic chest pain. There are no abnormal physical signs and her only risk factor is that she is taking the oral contraceptive pill long term. You wonder if a combination of clinical examination and the available d-dimer test (SimpliRED) would be suitable to rule out pulmonary embolism.

Search Strategy

Medline 1966-04/03 using the OVID interface.
[D-dimer.mp OR simplired.mp OR whole blood.mp] AND [exp thromboembolism OR exp pulmonary embolism OR PE.mp OR pulmonary embol$.mp OR pulmonary infarct$.mp] AND [exp"sensitivity and specificity".mp OR sensitivity.tw OR di.xs OR du.fs OR specificity.tw] LIMIT to human AND English.

Search Outcome

Altogether 272 papers were identified of which 5 were relevant and of sufficient quality.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Ginsberg JS et al, 1998, Canada	1250 consecutive referred patients to teaching hospital thromboembolic clinic with putative diagnosis of PE (73 lost to follow up)	Cohort	Diagnostic utility of a combination of low clinical probability of PE on clinical assessment with -ve SimpliRED d-dimer	Negative predictive value of 99%	Exclusion criteria 'lost' 484 of original 1881 patients screened then further 147 excluded due to non consent
Wells PS et al, 2000, Canada	1211 patients with presumptive diagnosis of PE broken into derivation and validation set	Diagnostic test	Sensitivity of clinical decision rule with addition of SimpliRED latex agglutination test in diagnosis of PE	87.8%-88.3% (validation-derivation)	Actual methodology not fully demonstrated e.g. gold standard definition predictive values and likelihood ratios not given
Farrell S, 2000, USA	198 patients presenting to US ED with suspected thromboembolic disease	Diagnostic test	Diagnostic utility of a combination of low clinical probability of PE on clinical assessment with -ve SimpliRED d-dimer	Negative predictive value 97% Sensitivity 84%	Estimation of clinical probability was with implicit not explicit methods 12% patients 'lost' in study
MacGillavry MR, 2001, Netherlands	404 adults, both in and out-patients in teaching hospitals with putative diagnosis of thromboembolic disease	Diagnostic test	Sensitivity and specificity of using a clinical probability and SimpliRED d-dimer test	Sensitivity 98% Specificity 11%	Over 50% exclusion rate for entry into study. Implicit methods only for determining clinical probability
Wells PS et al, 2001, Canada	946 adult patients referred for assessement of ? PE	Cohort	Diagnostic utility of a combination of low clinical probability of PE on clinical assessment with -ve SimpliRED d-dimer	Negative predictive value 99.5%	Investigation protocol violations occurred in nearly 10% of the patients

Comment(s)

Use of a bedside clinical decision rule for PE probability with the additional use of latex agglutination d-dimer testing results in high levels of sensitivity and high negative predictive values in the low PE risk groups. It is this group of patients that makes up the bulk of most patients with a putative diagnosis of PE. However latex agglutination d-dimers do not perform well in high or even moderate risk groups.

Clinical Bottom Line

Patients at low clinical risk with a negative bedside d-dimer can have pulmonary embolus ruled out.

References

1. 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):1006-11.
2. Wells PS, Anderson DR, Rodger M et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: Increasing the models utility with the SimpliRED d-dimer. Throm Haemost 2000;83(3):416-20.
3. Farrell S, Hayes T, Shaw M. A negative SimpliRED d-dimer assay result does not exclude the diagnosis of deep venous thrombosis or pulmonary embolus in emergency department patients. Ann Emerg Med 2000;35(2):121-5.
4. Mac Gillavry MR, Lijmer JG, Sanson BJ et al. Diagnostic accuracy of triage tests to exclude pulmonary embolism. Throm Haemost 2001;85(6):995-8.
5. Wells PS, Anderson D, Rodger M et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: Management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model Ann Intern Med 2001;135(2):98-107.