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Three Part Question

In a [patient with suspected pulmonary embolus] does the [does a negative IL D-dimer test] adequately [rule out the diagnosis]?

Clinical Scenario

A 30 year old woman presents to the emergency department with distressing, left sided pleuritic chest pain. She may have had a pulmonary embolism and you request a D-dimer. You know the lab in your hospital utilises the IL D-dimer test and wonder whether a normal result would be sufficiently sensitive to rule out a pulmonary embolus.

Search Strategy

Medline 1966-04/03 using the OVD interface.
([D-dimer.mp or exp Fibrin Fibrinogen Degredation Products or FDP.mp] AND [IL test.mp] AND [exp Thromboembolism or exp Pulmonary Embolism or pulmonary embol$.mp or PE.mp or pulmonary infarct$.mp or exp venous thromboembolism])

Search Outcome

6 papers were found from the above search. 4 were relevant. One further paper was found from hand searching journals and references. These 5 papers are shown in the table below.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Legani C et al, 1999, Italy	105 consecutive outpatients ?DVT	Prospective cohort	ROC curve to define max sensitivity of IL test	230ng/ml cut off sensitivity 100% specificity 77.2%	Patients ?DVT not PE High prevalence DVT Would not reflect an average emergency department population
van der Graaf F, 2000	99 ?DVT outpatients Comparison of 13 different D-dimer tests	Prospective cohort	IL test sensitivity	90%	Patients ?DVT not PE High prevalence of DVT
			IL test specificity	78%
Villa P et al, 2000, Spain	86 patients with a moderate or high clinical suspicion DVT	Prospective cohort	Iltest using 255ng/ml cut off sensitivity	98.4%	Patients suspected of having DVT not PE Cohort had high prevalence DVT Venography not used
			Iltest using 255ng/ml cut off specificity	33.3%
			Iltest using292ng/ml cut off sensitivity	95.2%
			Iltest using292ng/ml cut off	41.7%
			Gold EIA elisa test sensitivity	90%
			Gold EIA elisa test specificity	57.1%
Harper P et al, 2001, New Zealand	235 patients presenting to emergency department with ?DVT	Prospective cohort	IL test (250 ng/ml cut off) Sensitivity	94.1%	All patients presented as ?DVT not PE The gold standard venogram not used in diagnosis DVT All patients underwent ultrasound (USS), but not all underwent more than one. Probable under-estimation of DVT prevalence Patients were simply advised to return to the department if symptoms did not settle
			IL test (250 ng/ml cut off) SimpliRED sensitivity	66%
			IL test specificity	51.5%
			IL test SimpliRED specificity	75.6%
Kovacs MJ et al, 2001, Canada	All patients with suspected DVT (468 patients) or PE (525 patients), presenting to 4 hospitals	Prospective cohort	Simpli RED sensitivity	80%	Results combined for ?DVT and ?PE patients Cut off level of 200ng/ml was used for IL test (much lower than most labs)
			IL-test sensitivity	91%
			Acculot sensitivity	91%
			Simpli RED specificity	79%
			IL-test specificity	74%
			Acculot specificity	76%

Comment(s)

To date there have been few studies measuring the accuracy of this D-dimer test. Of note, there is almost no research looking in particular at patients presenting with symptoms of PE. The sensitivity of the IL test for ruling out DVT appears to lie somewhere between 90 and 100%. It is worth noting that all of these studies used a relatively low cut off level and it is worth being aware what the cut off level is in your hospital laboratory.

Clinical Bottom Line

The IL D-dimer test alone is not sufficiently sensitive to rule out pulmonary embolus. It must be used in conjunction with another test.

References

1. Legani C, Pancani C, Palareti G, et al. Performance of a new, fast D-dimer test (IL test d-dimer) for the management of outpatients with suspected deep vein thrombosis in emergency situations. Fibrinolysis and Proteolysis 1999;13(3):139-141.
2. van der Graaf F, van den Borne H, van der Kolk M et al. Exclusion of deep venous thrombosis with D-dimer testing--comparison of 13 D-dimer methods in 99 outpatients suspected of deep venous thrombosis using venography as reference standard. Thromb Haemst 2000;83(2):191-8.
3. Villa P, Ferrando F, Serra J, et al. Quantification of D-dimer using a new fully automated assay: its application for the diagnosis of deep vein thrombosis. Haematologica 2000;85(5):520-524.
4. Harper P, Marson C, Grimmer A, et al. The rapid whole blood agglutination d-dimer assay has poor sensitivity for use as an exclusive test in suspected deep vein thrombosis. N Z Med J 2001;114(1131):61–64.
5. Kovacs MJ, MacKinnon KM, Anderson D, et al. A comparison of three rapid D-dimer methods for the diagnosis of venous thromboembolism. Br J of Haem 2001;115(1):140-144.