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Three Part Question

In [emergency department patients with chest pain] can [D-Dimer ] [detect acute aortic dissection]?

Clinical Scenario

A 71-year-old female with a history of hypertension presents to the emergency department with a sudden onset of chest pain radiating to her back. Her ECG shows ischaemic changes and cardiac enzymes are pending. CXR shows a normal appearing mediastinum but clinical suspicion for a thoracic aorta dissection remains. You wonder if a D-Dimer assay has enough negative predictive value to exclude an acute thoracic aorta dissection (ATAD) to allow you to quickly anticoagulate this patient without any further imaging study.

Search Strategy

Medline 1950-08/07 using the OVID interface, Cochrane Library (2007)
[(exp Aneurysm, Dissecting/ or Aneurysm/ or aneurysm.mp.) OR (exp Aortic Aneurysm/ or exp Aortic Aneurysm, Thoracic/ or aortic dissection.mp.)] AND [(exp Fibrin Fibrinogen Degradation Products/ or fibrinogen degradation products.mp.) OR (d-dimer.mp.)] LIMIT to human AND English.

Search Outcome

95 papers found of which 88 were irrelevant or of insufficient quality.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Perez A et al April 2004 United States	156 patients with ATAD diagnosed in the ED. 7 also had D-dimer drawn at presentation. 16 excluded for missing data.	Retrospective chart review	Confirmed ATAD with elevated semi-quantitative D-dimer	All 7 patients with ATAD had elevated D-dimer (>500 ng/ml)	Retrospective study. Very few patients with ATAD had D-dimer drawn. Semi-quantitative D-dimer used, preventing determination of threshold that maximizes sensitivity/specificity. No control group.
Eggebrecht H et al Aug 2004 Netherlands	64 consecutive chest pain patients had D-dimer drawn. 32 asymptomatic patients with chronic ATAD served as control group.	Prospective cohort study	D-dimer in confirmed ATAD (>500 ng/ml).	All 16 patients with ATAD had higher D-dimer levels (2,238 +/- 1,765) than those with chronic ATAD (314), AMI (171), or chest pain (p<0.001). Cut off value 500 ng/ml yielded sensitivity of 100% (95% CI: 0.806 - 1.0) & specificity of 67% (95% CI: 0.483 -0.796).	Small number of patients Coincidence that 64 consecutive patients yielded 16 patients with ATAD, 16 with PE, 16 with AMI, & 16 with non cardiac chest pain?
Akutsu et al Dec 2006 Japan	78 consecutive patients with suspected AAD admitted to a coronary care unit who had a D-dimer assay at presentation. Later divided into ATAD (30) and non ATAD (48).	Prospective cohort study	Confirmed ATAD with elevated quantitative D-dimer	All 30 patients with ATAD had D-dimer >0.5 mcg/ml	Small number of patients. Not an emergency department setting.
Hazui H et al. Dec 2006 Japan	113 consecutive patients with ATAD who had a D-dimer assay at presentation.	Retrospective cohort study	Cut-off value 400 ng/ml. Compared sensitivity of D-dimer for detection of ATAD with and without thrombosed false lumen (TFL).	Sensitivity with TFL 86.4% (n=59), without TFL 98.1% (n=54). 9 AAD patients (8%) with normal D-dimer.	Small number of patients. Retrospective.
Hazui H et al June 2005 Japan	29 consecutive ATAD patients, 49 consecutive AMI patients. Performed Chest radiograph and D-dimer	Retrospective cohort study	Confirmed ATAD with elevated D-dimer.	Sensitivity 93.1% 2 patients with ATAD had D-dimer < 800 ng/ml. Both had a thrombosed false lumen	Small number of patients. Retrospective. Patients with acute aortic dissection of the descending aorta only were excluded.
Weber T et al May 2003 Austria	10 ED patients with suspected ATAD. Retrospectively studied 14 patients with confirmed diagnosis of AAD who also had D-dimer assay at presentation. 35 patients admitted with chest pain other than ATAD as a control group.	Prospective cohort study	Confirmed ATAD with elevated quantitative D-dimer. (>500 ng/ml)	D-dimer was elevated in all patients with ATAD (mean 9,400 ng/ml, range: 630-54,700 ng/ml). D-Dimer also elevated in 11/35 (31%) control group patients	Study does not clearly identify how many of the 10 prospectively studied patients had ATAD. Abstract states that ATAD was suspected in the 10 prospectively studied patients but in the methods section it states that all 10 of these patients had ATAD. It is impossible to estimate sensitivity & specificity based on one group of patients with known ATAD & another group not suspected of ATAD. This study does not clearly account for all of the patients enrolled.
Ohlmann P et al May 2006 France	94 consecutive patients admitted with confirmed ATAD who had D-dimer assay at presentation. 94 matched controls presenting with clinical suspicion of dissection which was later ruled out.	Retrospective Case-Control	Confirmed ATAD with elevated quantitative D-dimer	Sensitivity 99%. 93 of 94 patients had D-dimer >400 ng/ml. One false negative result: patient with TFL and D-dimer level of 300 ng/ml. 62 patients in control group (66%) had elevated D-dimer	Small number of patients. Retrospective.

Comment(s)

D-dimers are specific cross-linked fibrin derivatives that are the product of fibrinolytic degradation. They are considered the best available marker of coagulation activity and are well studied as a marker in the diagnosis of pulmonary embolism (PE). D-dimer would theoretically be elevated in thoracic aorta dissection due to exposure of the false lumen. Chronic thoracic aorta dissection would theoretically not produce significant elevation in D-dimer secondary to endothelialization of the false lumen. The clinical usefulness of screening laboratory test for ATAD has several clinical advantages. First, it would reduce the number of invasive diagnostic procedures as well as contrast induced nephropathy. Second, the rapid availability of the result would significantly reduce the time necessary to raise suspicion of ATAD. Third, a positive result could prevent patients from getting thrombolytic therapy when the underlying etiology of the patient's chest pain is ATAD. Finally, if the negative predictive value of D-dimer is high enough to exclude ATAD in patients with chest pain, anticoagulation could be initiated sooner in chest pain patients because treating physicians would not have to worry as much about ATAD masquerading as an acute coronary syndrome.

Clinical Bottom Line

Preliminary studies using D-Dimer to exclude clinically suspected ATAD show promise. Clearly, the sensitivity of D-dimer for ATAD falls when a thrombosed false lumen is present. Large prospective validation studies need to be done before D-dimer can be used to dictate clinical decision making in emergency department patients suspected of having ATAD.

References

1. Perez A et al. D-dimers in the emergency department evaluation of aortic dissection. Academic Emergency Medicine April 2004 11(4):397-400.
2. Eggebrecht H et al. Value of plasma fibrin D-dimers for detection of acute aortic dissection. Journal of the American College of Cardiology Aug 2004;44(4):804-9.
3. Akutsu K et al. A rapid Bedside D-Dimer Assay for Screening of Clinically Suspected Acute Aortic Dissection. Circulation Journal 69(4):397-403.
4. Hazui H et al. Young Adult Patients with Short Dissection Length and Thrombosed False Lumen....Liable to Have False-Negative Results of D-Dimer Testing for Acute Aortic Dissection Based on a Study of 113 Cases. Circulation Journal Dec 2006;70(12):1598-601.
5. Hazui H et al. Simple and Useful Tests for Discriminating Between Acute Aortic Dissection of the Ascending Aorta and Acute Myocardial Infarction in the Emergency Setting. Circulation Journal June 2005;69(6):677-82.
6. Weber T et al. D-dimer in acute aortic dissection. Chest May 2003;123(5):1375-8.
7. Ohlmann P et al. Diagnostic and Prognostic Value of Circulating D-Dimers in Patients with Acute Aortic Dissection. Critical Care Medicine May 2006;34(5):1358-64.