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© 2018 EDIZIONI MINERVA MEDICA International Angiology 2019 February;38(1):39-45


Online version at http://www.minervamedica.it DOI: 10.23736/S0392-9590.18.04006-3

ORIGINAL ARTICLE ITOR


AORTIC DISEASE

ED

’S
H

E
OIC

Effect of intraluminal thrombus on growth rate


of abdominal aortic aneurysms
Andrej DOMONKOS 1 *, Robert STAFFA 1, 2, Luboš KUBÍČEK 1, 2

1Faculty of Medicine, Masaryk University, Brno, Czech Republic; 2Second Department of Surgery, Center for Vascular
Disease, St. Anne’s University Hospital and Faculty of Medicine, Brno, Czech Republic
*Corresponding author: Andrej Domonkos, Faculty of Medicine, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.
E-mail: domonkos.andrej@gmail.com

ABSTRACT
Background:  Abdominal aortic aneurysm (AAA) includes a variety of morphologies with changing properties.
Growth rate is one of the most important factors directly linked to the risk of rupture. Intraluminal thrombus
(ILT) covering aortic wall is found in the majority of AAAs. Yet, its role in biomechanical processes in AAA
remains unclear. From one point of view ILT can serve as protective factor in reducing wall stress of AAA
and thus slow down the growth. Modern concept of multilayered ILT proved active inflammatory processes
inside, that can significantly affect the quality of the wall and thus lead to a higher growth rate and higher risk
of rupture. The goal of this study was to analyze the effect of ILT on growth rate of AAA and support one of
these theories.
Methods: Retrospective study of computed tomography angiography scans of AAA of 26 patients was
performed. Forty pairs of consecutive scans have been analyzed. Periods between two scans varied. Maximal
infrarenal diameter of AAA and size of ILT were measured. AAAs were split into 4 groups according to their
initial diameter. Growth rate was calculated for each AAA and linked to the relative size of ILT. These values
were statistically evaluated.
Results:  Negative correlation between relative size of ILT and growth rate was found (P=0.042062). This
significant result proved that thicker thrombus slowed down the growth of AAA and vice versa, smaller relative
size of ILT was linked to higher growth rate.
Conclusions:  This finding shows importance of ILT as one of the key factors influencing biomechanical
processes inside an AAA. Results of this study may contribute to future researches of this topic.
(Cite this article as: Domonkos A, Staffa R, Kubíček L. Effect of intraluminal thrombus on growth rate of ab-
dominal aortic aneurysms. Int Angiol 2019;38:39-45. DOI: 10.23736/S0392-9590.18.04006-3)
Key words:  Aortic aneurysm, abdominal - Thrombosis - Computed tomography angiography.

Vol. 38 - No. 1 International Angiology 39


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DOMONKOS EFFECT OF ILT ON GROWTH RATE OF AAA

A bdominal aortic aneurysm (AAA) is defined as a


dilatation of abdominal aortic diameter of 3.0 cm or
more.1-3 Other studies suggest defining AAA as the maxi-
role of the ILT — reducing wall stress slows down the
growth rate of AAA. Even more specific approach regards
the amount and individual configuration of ILT in affect-
mum infrarenal aortic diameter being at least 1.5 times ing the magnitude and distribution pattern of wall stress
larger than a diameter of unaltered part of abdominal in AAA.20 More recent concept of ILT focuses on active
aorta.4 Considering AAA epidemiology, males are at 4 to inflammation process in ILT. Layers of thrombus can pro-
5-time higher risk than women. Other important factors mote focal hypoxia in the vessel wall and weaken it.17 The
are hypertension, genetic predisposition, inflammation, system of canaliculi within ILT can transport molecules
smoking, and age.5, 6 White male smokers of age over 50 that induce the growth of AAA, as it was seen in animal
are at a prevalence of 5.9%.7 In the majority of the cases, models.21 These concepts offer opposite answers on the
AAA is an asymptomatic pathology. The most danger- basic question of this study — how does ILT affect growth
ous event that can occur, is its rupture, with a mortality of rate of AAA. The aim of this study was to compare these
30-50%, even if patient receives urgent treatment in spe- two theories and validate the role of ILT in AAA.
cialized center. Otherwise ruptured AAA leads to almost Risk of rupture is the most important clinical result re-
certain death.8 Risk of rupture is directly correlated with garding AAA. Growth rate is directly connected to the di-
diameter of AAA. Larger aneurysm diameter is a signifi- ameter and thus to the risk of the rupture. Understanding
cant and independent risk factor for AAA rupture.9, 10 the expansion process of AAA can lead to better under-
The growth rate is a very important factor in predict- standing of this topic. We were working with the hypothe-
ing risk of future rupture. Mean population data suggest, sis that ILT is directly affecting the growth rate of AAA. If
that AAA grows at an average rate between 2.5 to 7.9 ILT plays important role in growth of AAA future research
mm/year.11 These numbers may vary, even some portion can alter the view of this topic.
of AAAs can stay stable (11-58%).12 Dilatation of the
abdominal aorta is caused by mechanical hemodynamic Materials and methods
forces. When they exceed the wall strength of aneurysm,
growth continues.13 Wall quality and possible local dam- The aim of this study was to approach the topic of ILT in-
ages play huge role in growing of AAA. fluence in AAA growth rate from the clinical point of view.
Intraluminal thrombus (ILT) covers the wall of AAA in Measuring of important variables gathered from comput-
70% to 80% of the cases.14 The majority of all diagnosed ed tomography (CT) angiography scans was the primary
AAAs have ILT of variable size and overall layout. In the method used. This research was a retrospective study of
majority of cases ILT is located in the most dilated portion patients’ data who were under long-term surveillance in
of the aorta, thus does not have any significant influence our clinic.
on the dynamics of the blood flow (original lumen of aorta Twenty-six patients diagnosed with AAA were included
remains patent).15 Site of rupture of AAA can be localized in this study. These patients had growing AAA without any
in the thrombus covered portion of the wall. Studies sug- signs of rupture. Sample of patients was under surveillance
gest, that rupture in the wall underlying the thrombus can between October 2003 and January 2018. Each patient in-
occur in approximately 50% of the cases.16 If a fissure oc- cluded has undergone CT angiography at least twice. Peri-
curs inside ILT, direct bleeding into it can lead to immedi- ods between two consecutive scans varied from 2 months
ate rupture. Bleeding into ILT was observed significantly to 129 months. Average period between two scans was 24
more frequently in ruptured than in intact aneurysms of the months. One patient had undergone 3 CT scans, two had un-
same size.16 dergone 4 CT scans and one patient underwent 6 CT scans.
The current concept divides ILT into three layers — lu- In total we compared 40 consecutive CT scans. Scans
minal, medial and abluminar.17 Luminal layer is widely were analyzed by using TomoCon® PACS (Tatramed s.r.o.,
viewed as the most resistant, consisted of fibrin, leuko- Bratislava, Slovakia). This program allowed measuring of
cytes and erythrocytes. Abluminal layer (in contact with AAA diameter, length and surface with its native tools.
aortic wall) is associated with high protease activity.18 Each AAA and its ILT were measured by its length and
The exact role of ILT in the growth of AAA is still con- width. Describing a complex shape of AAA is very com-
troversial. Mechanical view of this topic describes ILT as plicated task. While trying to represent various formations
a protective layer that absorbs part of the radial force of of ILT, two main parts of AAA were chosen - plane of
blood pressure.19 This concept believes in the protective maximal diameter of AAA and plane of maximal size of

40 International Angiology February 2019


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cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
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EFFECT OF ILT ON GROWTH RATE OF AAA DOMONKOS

The time between two consecutive CT scans was cal-


culated. Widths the AAA was measured in the same plane
in both first and second CT scan and data were compared
to estimate the growth rate of each AAA. The growth rate
Absolute size of ILT
was calculated in widely accepted unit millimeters per
year. Each growth rate was associated with size of ILT. In
order to homogenize the sample of varying diameters and
thus varying sizes of ILT, relative size of ILT according to
Absolute diameter of AAA
diameter of AAA was calculated. The diameter of AAA
and the width of ILT were used to estimate the relative size
of ILT (Figure 2).
These calculations were made for both points estimated
in our measurements (plane of maximal diameter of AAA
and plane maximal size of ILT). To compare growth rate
Figure 1.—Measurements in the plane of maximal infrarenal diameter and associated value representing ILT, Pearson correlation
of AAA. coefficient was used.
In order to minimize the effect of faster growth in larger
AAA,6 AAAs were divided by maximal infrarenal diam-
eter and 4 artificial groups were created. These groups
included AAA with the range of diameters. Each group
Relative size of ILT
included range of 10 mm. 4 groups were created: group 1
from 30 mm to 39.99 mm, group 2 from 40 mm to 49.99
mm, group 3 from 50 mm to 59.99 mm, group 4 from 60
mm to 69.99 mm. Group 1 included 9 patients, group 2 in-
cluded 12 patients, group 3 included 3 patients and group
Diameter of AAA
4 included 4 patients. For each group average growth rate
in millimeters per year was calculated.

Results
Forty comparisons of consecutive CT angiography scans
of abdominal aorta were analyzed. Each comparison was
Figure 2.—Illustration of relative size of ILT according to diameter of
AAA. done between two scans. Average time between scans
were 24.31±23.38 months.
First set of comparisons was done in plane of maximal
ILT. Maximal diameter of AAA and diameter of ILT was diameter of AAA. The first scan was representing start-
measured in the first plane (Figure 1). The same procedure ing point and second scan was the end point of growing
was done in plane of maximal size of ILT. All of the mea- AAA. Two scans were compared to calculate growth rate
surements were done in millimeters to stay as accurate as (standardly in millimeters per year). Average maximal di-
possible. ameter of AAA in the first of two consecutive scans (start-
Apart from width of AAA and ILT, surface of AAA and ing point) was 49.16±10.13 mm. Average diameter in the
ILT were covered in each part. These measurements were second scan (end point) was 56.64±13.45 mm. Average
done with TomoCon® tool for measuring surface. Work- growth rate through the whole set of analyzed AAAs was
ing in two-dimensional field of CT scan offered possibility 4.48±3.89 mm per year.
to approach relative size of ILT from other perspective. Second set of comparisons was done in plane of maxi-
Length of AAA and its ILT was also measured from CT mal size of ILT. Average diameter in the starting point of
images. CT angiography scans we used, were done in gaps AAA was 47.68±9.44 mm. Average diameter in the end
of 5 mm. This measurement served as proof of examina- point was 55.41±12.59 mm. Average growth rate in this
tion of whole AAA, not just its parts. plane was 4.43±3.98 mm per year.

Vol. 38 - No. 1 International Angiology 41


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or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access
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cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
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DOMONKOS EFFECT OF ILT ON GROWTH RATE OF AAA

Apart from transverse view of AAA, frontal plane in each


6
case was analyzed. Average length of AAA was 86.10±25.34
mm. Average length of ILT was 76.27±29.07 mm. These
Growth rate (mm per year)

5.5
Group 3 Group 4
values represent varying morphology of each AAA and
heavily depend on individual anatomy of each patient.
5

Growth rate according to maximal diameter


4.5 Group 2
Group 1 In order to fully understand basic growth mechanism of
AAA groups were created according to maximal diam-
4
eter. Each group included a range of maximal infrarenal
3.5
diameters. Average growth rate in millimeters per year
(30-39.99) (40-49.99) (50-59.99) (60-69.99) was calculated for each group (Table I). Group 1 had the
Group range (mm) slowest average growth rate 3.85 mm per year, whereas
group 4 had the highest one with 5.87 mm per year. Aver-
Figure 3.—Correlation between increased growth rate and maximal in- age growth rate was increasing with the maximal infrare-
frarenal diameter.
nal diameter (Figure 3).
Growth rate according to relative size of ILT
9.5 Average absolute size of ILT in the first set of CT scans
8.5 was 16.11±8.73 mm. We believe that absolute size of ILT
Growth rate (mm per year)

7.5 cannot represent the actual morphology of AAA. Large


6.5 aneurysm with only thin ILT and vice versa small aneu-
5.5 rysm with thick thrombus cannot be compared by absolute
4.5 size of ILT. Therefore, relative size of ILT was calculated.
3.5 Absolute diameter of AAA in its widest point (plane of
2.5 maximal diameter of AAA) and absolute size of ILT was
1.5 compared. Average relative size of ILT was 33.28±16.95%.
0.5 Relative size of ILT from the first scan and average
5% 15% 25% 35% 45% 55%
growth rate per year were compared. These two set of data
Relative size of ILT
did correlate. Negative correlation between size of throm-
Figure 4.—Linear correlation between relative size of ILT and growth bus and growth rate was found. Pearson correlation coef-
rate in plane of maximal infrarenal diameter.
ficient in our set was r=-0.324. This result is significant at
P<0.05 (P=0.042062) (Figure 4).
The same procedure was done in the second plane of
9.5 our measurements, plane of AAA with maximal size of
8.5 ILT. Average relative size of ILT was 36.88±16.36%. Pear-
Growth rate (mm per year)

7.5 son correlation coefficient was r=-0.230968027. Although


6.5 negative correlation was found, this result has not been
5.5 proven significant (Figure 5).
4.5

3.5
Table I.—Groups of AAAs sorted by maximal infrarenal diam-
2.5 eter.
1.5
Size range of maximal
Group number Growth rate (mm per year)
0.5 infrarenal diameter (mm)
5% 15% 25% 35% 45% 55%
1 30-39.99 3.86
Relative size of ILT 2 40-49.99 4.81
3 50-59.99 4.95
Figure 5.—Linear correlation between relative size of ILT and growth
4 60-69.99 5.87
rate in plane of maximal size of ILT.

42 International Angiology February 2019


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or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access
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EFFECT OF ILT ON GROWTH RATE OF AAA DOMONKOS

Growth rate according to surface have been biased by the varying position of each patient.
Not all the scans could provide the exact reconstruction of
Average surface of AAA in point of maximal diameter in
aorta in axial plane. In 100% of the cases, ILT was found.
the first set of CT scans was 19.31±8.49 mm2. Average
Majority of AAAs do have an ILT of various morphology.
surface of ILT was 9.06±8.29 mm2. Relative surface of
In our sample, ILT was most often found in the neck of
ILT (in comparison to the absolute surface of AAA) was
AAA and its size did vary mainly due to the diameter of
44.84±23.52%. With these values we were able to calcu-
each part of AAA. ILT did cover nearly whole length of
late absolute and relative surface of the aneurysm without
AAA and in some cases covered one or both of iliac arter-
ILT (i.e. surface of blood flow). Absolute surface of blood-
ies. Differences in initial ILT diameter were find in each
flow was 10.24±5.68 mm2. Relative surface of bloodflow
individual case of AAA. Although 4 groups represented
was estimated at 55.16±23.52%. No correlation was found
different starting diameters, initial morphology of ILT was
between surface of ILT or the blood flow and growth rate
varying in each AAA. It is not possible to predict size or
of AAA.
shape of ILT according to maximal infrarenal diameter of
AAA. Mean population data suggest, that ILT is found in
Discussion
majority of AAAs.14 It was proven to play important role
We worked with data collected through years 2013-2018 in biomechanics of aneurysms. We believe that following
and used at least two consecutive CT angiography scans results contributes to this statement.
from each patient. Time between two scans varied mainly At the beginning of the study we posed a very sim-
due to individuality of each case. Consecutive CT scans ple question. How does ILT affect growth rate of AAA?
were done with irregular frequency. Shortest period be- Sometimes the simplest questions have very complicated
tween 2 scans was 2 months, the longest period was almost answers. To represent varying morphology of aneurysms
11 years. Average time between scans was 24 months. In we have chosen to work with CT angiography scans. Us-
order to homogenize the sample, we calculated average ing two vertical scans, we have calculated average growth
growth rate in millimeters per year. Some patients had rate for each pair of AAAs. We used millimeters per year
not come for planned CT scan, others had other diagnosis to represent sheer speed of expansion. To homogenize our
that were more urgent at the time. Our study included also sample we used relative size of ILT in vertical plane.
AAAs that were bigger than 5.5 cm (the threshold for sur- Using method of calculating surface of ILT in vertical
gery).22 One patient had declined, others were not able to plane had not proven itself in being accurate enough to
undergo open surgery nor endovascular intervention due to produce any significant results. Surface of measured ob-
high risk comorbidities (mainly malignity). Primary goal jects does not correlate with growth rate in any case and it
in searching data was to find AAAs that had multiple CT should not be used in this specific case. Two dimensional
scans. Due to the fact that most of our patients with maxi- CT scans had best accuracy while measuring length, com-
mal AAA diameter bigger than 5.5 cm would pass only puting the surface did not represent the exact morphol-
one CT examination, it was uneasy to collect sample large ogy of AAA nor ILT in a single plane. We believe that
enough to deliver significant results. Patients with AAA this method of representing correlation between ILT and
smaller than 5.5 cm would always undergo second CT growth rate is not suitable for future research.
scan after 6 months from the first one in order to estimate The plane of maximal diameter of AAA was (in our
growth rate and possibly intervene on rapid growing an- study) proven to have the highest growth rate. In minority
eurysm (AAA with growth rate over 5 mm in 6 months).22 of the cases, plane of maximal size of ILT did not corre-
AAAs with diameter larger than 5.5 cm are considered to spond with the plane of maximal diameter. Nevertheless,
undergo an intervention. diameter of AAA in both of these planes grew in negative
Average growth rate of our sample matches values de- correlation with the size of ILT. Plane of maximal diameter
scribed in the literature sources. Analyzing 4 groups di- was the one of truly representing the total growth rate of
vided by size of AAA we found correlation between maxi- AAA, the most important value for us. In this plane ILT
mal infrarenal diameter and growth rate. Larger diameter had shown significant statistical value. We used Pearson
associated with higher growth has been reported in other correlation coefficient in order to support our findings. We
studies.23-25 were comparing absolute growth rate of AAA with relative
Morphology of our aneurysms did vary. This was caused size of ILT. The covariance of these two variables proved
by wide sample of diameters. Average length of AAA may to be a linear correlation. From our heterogenous sample

Vol. 38 - No. 1 International Angiology 43


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or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access
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cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically

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DOMONKOS EFFECT OF ILT ON GROWTH RATE OF AAA

of AAAs of various sizes and morphology, we can claim negative correlation between the relative size of ILT and
that growth rate in maximal diameter had been influenced the growth rate of AAA. Of course, thrombus is not the
by the size of ILT. only element influencing growth rate. Nevertheless many
This result stands in between of two views of this topic articles that have been published in the literature manifest
as is mentioned in the literature. Inflammatory activity in that its significance is unquestionable. We believe that
ILT can degrade the quality of the aortic wall and reduce its such complex topic as AAA, cannot be viewed only by
resistance against the hemodynamic forces. ILT modify the the maximal diameter. Numerous factors play a role ei-
wall stress and strength as it has been proven before.26-29 ther in its growth or the rupture risk and ILT is surely one
Simplified mechanical view of ILT as protective layer over of them. All the scientific findings regarding the topic of
the wall, on the other hand, states that thrombus can serve ILT should be taken into consideration before deciding on
as a protective factor in reducing wall stress.19 Acknowl- one unanimous answer of its role. Future research in this
edging both of these views, we cannot accept one and com- topic is needed to be done in order to fully understand all
pletely deny the other. Findings of both approaches should mechanical and biological processes affecting AAA. Bet-
be considered in the modern understanding of this topic.20 ter understanding of this pathology can lead to personal
approach to each diagnose and it can offer individual treat-
Limitations of the study ment options for the patients.
Results of our research are limited by the size of our sam-
ple. Patients who underwent CT angiography scans with
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44 International Angiology February 2019


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EFFECT OF ILT ON GROWTH RATE OF AAA DOMONKOS

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Conflicts of interest.—The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manu-
script.
Authors’ contributions.—Robert Staffa and Luboš Kubíček conceived the presented idea; Andrej Domonkos developed the theory and performed the
computations; Luboš Kubíček verified the analytical methods. All authors discussed the results and contributed to the final manuscript.
Article first published online: November 7, 2018. - Manuscript accepted: October 29, 2018. - Manuscript received: April 5, 2018.

Vol. 38 - No. 1 International Angiology 45

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