D-dimer level remains a highly sensitive test for acute aortic dissection beyond the first 24 hours after onset

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D-dimer level remains a highly sensitive test for
acute aortic dissection beyond the first 24 hours
after onset
Scott A. LeMaire, Ludivine Russell, Neal R.
Barshes, Paul M. Allison, Dana E. Haas, Ying H.
Shen, Dianna M. Milewicz, Joseph S. Coselli
AATS Aortic Symposium 2010 ? New York ? April
29-30, 2010
This study describes an unlabeled/investigational
use of the Siemens Advanced D-dimer Assay, i.e.
for the diagnosis of acute aortic dissection.
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Study Objective

• D-dimer has been proposed as a highly sensitive
  biomarker to detect acute aortic dissection
• Elefteriades et al ? Cardiology 2008
• Recent data from the International Registry of
  Acute Aortic Dissection Substudy on Biomarkers
  (IRAD-Bio) show that D-dimer levels obtained
  within the first 24 hours after symptom onset had
  a 96.6 sensitivity
• Suzuki et al ? Circulation 2009

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Study Objective

• Some patients, particularly those with atypical
  symptoms, present for evaluation beyond the first
  24 hours after onset of acute aortic dissection
  it is unclear whether D-dimer levels would be
  useful in detecting dissection in these patients
• The purpose of this study was to determine
  whether D-dimer levels remain elevated more than
  24 hours after the onset of acute aortic
  dissection

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Methods

• Institutional approval was obtained for the
  study, and written informed consent was obtained
  from all patients
• Plasma samples were collected within 10 days
  after onset of symptoms from 100 patients with
  unrepaired acute aortic dissection
• Whenever possible, serial samples were obtained
  over a period of 2 or more days
• Samples were grouped according to day of
  collection relative to the onset of aortic
  dissection an average of 25 samples were
  available for each days group, from day of onset
  (day 0) through post-dissection day 10

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Clinical Features
Variable Patients (n 100)
Age (yrs), mean SD 56 14
Men 61
Hypertension 62
Coronary artery disease 4
Diabetes 10
Chronic obstructive pulmonary disease 11
Smoking (past or current) 54
Marfan syndrome 15
Cancer 3
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Dissection Characteristics
Variable Patients (n 100)
DeBakey classification Type I Type II Type III 50 12 38
Classic aortic dissection 94
Intramural hematoma 6
Penetrating atherosclerotic ulcer 0
Drug-induced aortic dissection 1
Iatrogenic aortic dissection 1
Aortic rupture 9
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Methods

• D-dimer levels were measured in the clinical
  laboratory by using the Siemens Advanced D-dimer
  assay (latex-enhanced immunoturbidimetric assay)
  on an automated coagulation analyzer BCS XP
  (range of detection, 0.4-55 µg/mL)
• The approved cut-off for detecting venous
  thromboembolism for this assay is 1.6 µg/mL this
  value was used as the diagnostic threshold
• A post-hoc subgroup analysis was performed to
  explore whether clinical factors were associated
  with false-negative D-dimer levels in this cohort

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Results
40.0
35.0
30.0

• The median D-dimer level for all plasma samples
  (n 279) was 3.56 µg/mL (interquartile range,
  2.55-5.60 µg/mL)
• D-dimer levels exceeded the 1.6 µg/mL diagnostic
  threshold in 266 samples, yielding an overall
  sensitivity of 95.3

25.0
20.0
D-dimer levels (µg/mL)
15.0
10.0
1.6 µg/mL threshold
5.0
0.0
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D-dimer levels remained markedly elevated
throughout the 10-day post-dissection period
daily sensitivities ranged from 89 to 100
40.0
35.0
30.0
25.0
D-dimer levels (µg/mL)
20.0
15.0
10.0
1.6 µg/mL threshold
5.0
0.0
Days after onset 0 1 2 3 4
5 6 7 8 9
10 n 7 27
26 33 26 27 27
30 31 21 24 Sensitivity
100 89 89 94 100 100 96
97 97 95 96
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• False-negative results were significantly more
  common in samples obtained from patients without
  hypertension, with a history of coronary artery
  disease, or with DeBakey type II dissection
• False-negative results did not appear to be
  related to patient age, intramural hematoma (vs
  classic dissection), Marfan syndrome, smoking, or
  cancer

Factor False-negative Rate (D-dimer 1.6 µg/mL) P
Hypertension Yes No 5/190 (3) 8/89 (9) 0.02
Coronary artery disease Yes No 4/20 (20) 9/259 (3) 0.009
DeBakey type I II III 2/84 (2) 4/21 (19) 7/174 (4) 0.004
Intramural hematoma Yes No 1/17 (6) 12/262 (5) 0.6
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Conclusions

• Elevated D-dimer levels remain a sensitive
  indicator of acute aortic dissection throughout
  the first 10 days after onset
• Post-hoc analysis showed that the sensitivity of
  D-dimer may be reduced in certain subsets of
  patients, such as those with dissection involving
  only the ascending aorta (ie, DeBakey type II)
• Although D-dimer testing may be helpful in
  detecting acute aortic dissection in patients
  with delayed presentation, further studies are
  needed to evaluate the impact of clinical factors
  on the sensitivity of this assay

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Acknowledgements

• Dr. LeMaire is supported by a Thoracic Surgery
  Foundation for Research and Education/National
  Heart, Lung and Blood Institute Co-sponsored
  Mentored Clinical Scientist Development Award
  (K08 HL080085)
• The Thoracic Aortic Disease Tissue Bank at Baylor
  College of Medicine is supported in part through
  the NIH Specialized Center for Clinically
  Oriented Research in Thoracic Aortic Aneurysms
  and Dissections (P50 HL083794 DM Milewicz, PI)