D-Dimer in Aortic Dissection
D-Dimer in Aortic Dissection
Abstract & Commentary
By Michael H. Crawford, MD. This article originally appeared in the July 2009 issue of Clinical Cardiology Alert. It was peer reviewed by Ethan J. Weiss, MD.
Source: Suzuki T, et al. Diagnosis of acute dissection by D-Dimer: The international registry of acute aortic dissection substudy on biomarkers (IRAD-Bio) experience. Circulation. 2009;119:2702-2707.
The differential diagnosis of acute chest pain includes three entities that can be lethal if missed: myocardial infarction (MI), pulmonary embolus, and aortic dissection. The latter is least common, so a simple test to exclude it would be of value. D-dimer has proven useful to exclude pulmonary embolus, and it has been noted to be elevated in aortic dissection. Thus, this international registry study of aortic dissection tested the hypothesis that a normal D-dimer would exclude the diagnosis of aortic dissection. In 14 institutions around the world, patients presenting within 24 hours of symptoms suspicious for aortic dissection had D-dimer tests and an aortic imaging study. There were 220 patients enrolled, 87 with aortic dissection and 133 with other diagnoses (46 MI, 37 unstable angina, 5 pulmonary embolism, and 45 other diagnoses). D-dimer was markedly elevated (> 3,000 ng/mL) in aortic dissection, as compared to MI (1,459), angina (760), pulmonary embolus (2,452), and other diagnoses (1,399). The negative predictive value of a < 500 ng/mL cut off for D-dimer vs. all other diagnoses was 98%, with a negative likelihood ratio of 0.07 for 24 hours. In patients with aortic dissection presenting within six hours of symptom onset, a D-dimer > 1,600 was only observed in dissection. It rises above 1,600 in MI at 6-12 hours and pulmonary embolism at 12-24 hours. Suzuki et al conclude that D-dimer may help exclude aortic dissection in patients who present within 24 hours of the onset of suspicious symptoms.
Acute aortic dissection is a relatively rare but highly lethal disease. Without sophisticated imaging, the diagnosis is difficult to make and, thus, can become a highly litigated misdiagnosis. A simple blood test to exclude the diagnosis would be very useful. The observation that D-dimer was elevated in patients with known dissection does not establish its role in evaluating patients without known disease. This study sought to clarify this issue by studying its value in triaging patients with chest pain syndromes suspicious for aortic dissection clinically. In this population, the negative predictive value in the first 24 hours from symptom onset was 98%, and the positive predictive value was 45%. Clearly, this seems like a useful test to exclude the diagnosis and eliminate ordering costly imaging studies. As an added bonus, a negative D-dimer also excludes pulmonary embolus.
However, there are several limitations and caveats with this study. The most obvious is that this is a small study by cardiology trial standards. Importantly, they did not study everyone in the emergency department with chest pain; an imaging study was only ordered for those with a high enough suspicion for dissection. It is possible that the negative predictive value would not be as good in a less select patient group. For example, it is known that D-dimer levels are lower if the false lumen is clotted off. Also, D-dimer levels may not be elevated in intramural hematoma, a precursor to dissection. In addition, D-dimer may be elevated in chronic aortic dissection. Although the very high levels of D-dimer observed in the dissection patients who presented within six hours of symptom onset were impressive, the diagnostic accuracy vs. pulmonary embolus was not tested, and there were insufficient numbers for such an analysis.
For now, I will be reassured if the D-dimer is negative in a chest pain patient, and will focus more on ischemic heart disease diagnosis instead of dissection and pulmonary embolus. However, if suspicion persists for these alternative diagnoses, a low threshold for imaging studies should be maintained. Hopefully, further studies will clarify the broader role of D-dimer in acute chest pain patients. Finally, this study was carried out in centers selected for their expertise in the diagnosis and management of aortic dissection. Different results could be obtained in other, less specialized centers.The differential diagnosis of acute chest pain includes three entities that can be lethal if missed: myocardial infarction (MI), pulmonary embolus, and aortic dissection.
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