D-Dimer in Aortic Dissection Workup
- Aortic Dissection is a cleavage of the aortic media layer created by a dissecting column of blood. This is different pathologically than an aortic aneurysm but the two terms are frequently interchanged incorrectly
- Uncommon => 2-4 per 100,000 person-years (Acute Coronary Syndromes is about 100-200 times more common)
- About 1 of every 2,000 ED patients presenting with any symptom associated with thoracic aortic dissection (TAD) will have TAD
- Life-threatening – mortality rate of 1.2% per hour in the first 48hr
Recap / Basics
- Three variants
- Intimal Flap tear – ~70-80% of cases
- Intramural hematoma (believed to start from rupture of the vasa vasorum) – ~10-15%
- Penetrating atherosclerotic ulcer – ~10-15%
- Risk Factors
- Hypertension – 72%
- Collagen disorders – Marfan’s, Ehlers-Danlos
- Inflammatory vasculitis disorders – Giant cell arteritis, Takayasu arteritis, rheumatoid arthritis
- Instrumentation or structural abnormalities – cardiac cath / CABG, bicuspid valve, aortic coarctation, valve replacement
- Type A – Ascending and Arch
- Higher Mortality
- Surgical Management
- Type B – descending; Below the left subclavian
- Lower Mortality
- Often medical management
- I – Ascending, arch and possible descending
- II – Ascending only
- III – Descending aorta
- Pain is common >90%
- Abrupt ~85%, excruciating (“worst ever”) ~90% and most severe at onset
- Chest or Back
- Sharp, tearing, ripping but may be pressure or crushing
- Migration suggests dissection but occurs only ~ 30% of cases
- Physical exam, ECG, and chest x-ray are insufficiently sensitive to help with diagnosis
- Other advanced imaging needed
- Contrast CT Chest – sensitivity ~100%, specificity ~98%
- MRI – sensitivity ~98%, specificity ~98%
- Transesophageal Echocardiography (TEE) – sensitivity ~98%, specificity ~95%
- ED treatment is to reduce blood pressure to target systolic BP = 100-120
- β-blockers – Esmolol or labetalol
- Sodium nitroprusside
- Surgery generally performed for Type A and complicated Type B dissections and possibly other Type Bs
- Medication management for uncomplicated Type B
- Can the D-dimer help to include or exclude patients who might need advanced imaging?
- The D-dimer is a fibrin degradation product indicating recent or ongoing coagulation
- The D-dimer is very sensitive for picking up most dissections. Data from several different pooled studies show sensitivity 94-97%, specificity 34-100%
- This has led several authors to suggest the D-dimer seems to have value as a screening tool for “ruling out” acute aortic dissection; i.e. if the D-dimer result is below a threshold level (generally below 400 – 500 ng/mL), then TAD is unlikely
- However, false negatives (D-dimer levels below the threshold in patient with documented TAD) have been reported in several papers and one paper (Paparella) reported a surprising high false negative rate of 18% (11/61) with time of symptom onset to diagnosis ranging from 2 – 72 hours
- Other authors have suggested the D-dimer should be part of the work-up if TAD is suspected. However using the D-dimer alone would lead to an unacceptably high number of false positives and follow-up advanced imaging
- Higher d-dimer levels correlate with more segments of the aorta involved, with false lumen type dissections, and with higher mortality rates
- D-dimers seem to be lower in patients with intramural hematomas
Bottom Line / Pearls & Pitfalls
- A negative D-dimer (< 400 ng/mL) makes TAD unlikely but it is not 100% and false negatives occur
- A positive D-dimer occurs in a very high percent of patients with TAD but also occurs in many other conditions
- What is needed is a well-tested clinical decision rule to help select patients for further testing; that is when should we order, or not order, a D-dimer and/or when should we order, or not order, advanced imaging
Discussion Questions / Future Exploration
- Can we develop decision rules similar to those developed for pulmonary embolus?
- Are there time limits related to D-dimer testing: when is it too soon or too late after symptoms onset for the test to be useful?
- Is there a better threshold level for D-dimer which might make it a more useful test?
- Brown MD, Newman DH. Evidence-based emergency medicine. Can a negative D-dimer result rule out acute aortic dissection? Ann Emerg Med. 2011; 58(4): 375-6.
- Fan Q, Wang W, Zhang Z, et al. Evaluation of D-dimer in the diagnosis of suspected aortic dissection. Clin Chem Lab Med. 2010;48(12):1733-1737.
- Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD): new insights into and old disease. JAMA 2000;283:897-903.
- Klompas M. Does this patient have an acute thoracic aortic dissection? JAMA. 2002;287:2262-72.
- Manning WJ. Clinical manifestations and diagnosis of aortic dissection. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA 2014. Retrieved from http://www.uptodate.com/.
- Marill KA. Serum D-dimer is a sensitive test for the detection of acute aortic dissection: a pooled meta-analysis. J Emerg Med. 2008; 34(4):367-76.
- Ohlmann P, et al. Diagnostic and prognostic value of circulating D-Dimers in patients with acute aortic dissection, Crit Care Med, 2006; 34(5):1358-64.
- Paparella D, et al. D-dimers are not always elevated in patients with acute aortic dissection. J Cardiovasc Med (Hagerstown) 2009;10:212-4.
- Sodeck G; et al. D-dimer in ruling out acute aortic dissection: a systematic review and prospective cohort study. Eur Heart J; 2007; 28(24):3067-75.
- 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(20);2702-7.
- Shimony A, Filion KB, Mottillo S, et al. Meta-analysis of usefulness of d-dimer to diagnose acute aortic dissection, Am J Cardiol 2011; 107(8):1227-34.
- Taylor RA, Iyer NS. A decision analysis to determine a testing threshold for computer tomography angiography and D-dimer in the evaluation of aortic dissection. Am J Emerg Med. 2013;31(7):1047-55.
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