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.
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
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
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 day’s group, from day of
onset (day 0) through post-dissection day 10
Clinical Features
Variable
Age (yrs), mean ± SD
Patients
(n = 100)
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
Dissection Characteristics
Patients
(n = 100)
Variable
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
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
40.0
Results
35.0
• D-dimer levels exceeded the
1.6 µg/mL diagnostic threshold
in 266 samples, yielding an
overall sensitivity of 95.3%
25.0
D-dimer levels (μg/mL)
• The median D-dimer level for
all plasma samples (n = 279)
was 3.56 µg/mL (interquartile
range, 2.55-5.60 µg/mL)
30.0
20.0
15.0
10.0
5.0
0.0
1.6 µg/mL
threshold
D-dimer levels remained markedly elevated throughout the 10-day
post-dissection period; daily sensitivities ranged from 89 to 100%
40.0
D-dimer levels (μg/mL)
35.0
30.0
25.0
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
97%
97%
95%
96%
Sensitivity
100% 89% 89%
94% 100% 100% 96%
• 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
Hypertension
Coronary artery disease
DeBakey type
Intramural hematoma
Yes
No
Yes
No
I
II
III
Yes
No
False-negative Rate
(D-dimer ≤ 1.6 µg/mL)
5/190 (3%)
8/89 (9%)
4/20 (20%)
9/259 (3%)
2/84 (2%)
4/21 (19%)
7/174 (4%)
1/17 (6%)
12/262 (5%)
P
0.02
0.009
0.004
0.6
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
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)