Professional Documents
Culture Documents
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
COPYRIGHT 2019 EDIZIONI MINERVA MEDICA
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
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
ED
’S
H
E
OIC
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.
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
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.
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
5.5
Group 3 Group 4
values represent varying morphology of each AAA and
heavily depend on individual anatomy of each patient.
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.
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
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
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
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
References
suspected AAA did not have measured blood pressure im-
mediately before the CT examination in their medical re- 1. Wanhainen A, Themudo R, Ahlström H, Lind L, Johansson L. Tho-
racic and abdominal aortic dimension in 70-year-old men and women—a
cords. Thus, we were not able to include blood pressure as population-based whole-body magnetic resonance imaging (MRI) study.
one of the main factors influencing the growth rate and the J Vasc Surg 2008;47:504–12.
risk of rupture of AAA. These findings induced custom- 2. Steinberg I, Stein HL. Arteriosclerotic abdominal aneurysms. Report
of 200 consecutive cases diagnosed by intravenous aortography. JAMA
ization of our AAA protocol to routinely the blood pres- 1966;195:1025–9.
sure before each CT angiography scan performed in patient 3. McGregor JC, Pollock JG, Anton HC. The value of ultrasonography in
with suspected AAA. To represent growth of AAA we have the diagnosis of abdominal aortic aneurysm. Scott Med J 1975;20:133–7.
chosen growth in its specific part. We found highest growth 4. Sterpetti AV, Schultz RD, Feldhaus RJ, Cheng SE, Peetz DJ Jr. Factors
influencing enlargement rate of small abdominal aortic aneurysms. J Surg
rate in the plane of maximal diameter. This led us to calcu- Res 1987;43:211–9.
late the relative size of ILT and finding specific correlation. 5. van Vlijmen-van Keulen CJ, Pals G, Rauwerda JA. Familial abdominal
aortic aneurysm: a systematic review of a genetic background. Eur J Vasc
The results of this study suggest that ILT may serve as Endovasc Surg 2002;24:105–16.
a protective factor in question of sheer growth of AAA in 6. Vardulaki KA, Walker NM, Day NE, Duffy SW, Ashton HA, Scott RA.
its maximal diameter. Our findings indicate that AAA with Quantifying the risks of hypertension, age, sex and smoking in patients
with abdominal aortic aneurysm. Br J Surg 2000;87:195–200.
smaller thrombus will grow faster than AAA with the big-
7. Pleumeekers HJ, Hoes AW, van der Does E, van Urk H, Hofman A,
ger one. These clinical findings may be confronted with de Jong PT, et al. Aneurysms of the abdominal aorta in older adults. The
mathematical calculations in order to fully understand bio- Rotterdam Study. Am J Epidemiol 1995;142:1291–9.
mechanical processes in AAA. This can be done by using 8. [No authors listed]. Mortality results for randomised controlled trial of
early elective surgery or ultrasonographic surveillance for small abdomi-
FE (finite element) modeling and furthermore biomechani- nal aortic aneurysms. The UK Small Aneurysm Trial Participants. Lancet
cal indices like PWS (peak wall stress) and PWRR (peak 1998;352:1649–55.
wall rupture risk).30 Future research of this topic is needed 9. Brown PM, Sobolev B, Zelt DT. Selective management of abdominal
aortic aneurysms smaller than 5.0 cm in a prospective sizing program with
to bring significant results that can alter the view of ILT in gender-specific analysis. J Vasc Surg 2003;38:762–5.
AAA. 10. Brown LC, Powell JT. Risk factors for aneurysm rupture in patients
kept under ultrasound surveillance. UK Small Aneurysm Trial Partici-
pants. Ann Surg 1999;230:289-97.
Conclusions 11. Wolf YG, Thomas WS, Brennan FJ, Goff WG, Sise MJ, Ber-
nstein EF. Computed tomography scanning findings associated
This paper is meant to represent a different approach to with rapid expansion of abdominal aortic aneurysms. J Vasc Surg
the topic of ILT in AAA. Main conclusion of this study 1994;20:529-38.
is significance of ILT in very complex subject of AAA 12. Nevitt MP, Ballard DJ, Hallett JW Jr. Prognosis of abdomi-
nal aortic aneurysms. A population-based study. N Engl J Med
growth rate. In our sample we have proven that ILT plays a 1989;321:1009–14.
significant role in growth of AAA. We found a significant 13. Zambrano BA, Gharahi H, Lim C, Jaberi FA, Choi J, Lee W, et al.
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
Association of Intraluminal Thrombus, Hemodynamic Forces, and Ab- 22. Moll FL, Powell JT, Fraedrich G, Verzini F, Haulon S, Waltham M,
dominal Aortic Aneurysm Expansion Using Longitudinal CT Images. Ann et al.; European Society for Vascular Surgery. Management of abdominal
Biomed Eng 2016;44:1502–14. aortic aneurysms clinical practice guidelines of the European society for
14. O’Leary SA, Kavanagh EG, Grace PA, McGloughlin TM, Doyle BJ. vascular surgery. Eur J Vasc Endovasc Surg 2011;41(Suppl 1):S1–58.
The biaxial mechanical behaviour of abdominal aortic aneurysm intralu- 23. Stonebridge PA, Draper T, Kelman J, Howlett J, Allan PL, Prescott
minal thrombus: classification of morphology and the determination of R, et al. Growth rate of infrarenal aortic aneurysms. Eur J Vasc Endovasc
layer and region specific properties. J Biomech 2014;47:1430–7. Surg 1996;11:70–3.
15. Biasetti J, Hussain F, Gasser TC. Blood flow and coherent vortices in 24. Brady AR, Thompson SG, Fowkes FG, Greenhalgh RM, Powell
the normal and aneurysmatic aortas: a fluid dynamical approach to intra- JT; UK Small Aneurysm Trial Participants. Abdominal aortic aneurysm
luminal thrombus formation. J R Soc Interface 2011;8:1449–61. expansion: risk factors and time intervals for surveillance. Circulation
16. Roy J, Labruto F, Beckman MO, Danielson J, Johansson G, Swe- 2004;110:16–21.
denborg J. Bleeding into the intraluminal thrombus in abdominal aortic 25. Thompson AR, Cooper JA, Ashton HA, Hafez H. Growth rates of
aneurysms is associated with rupture. J Vasc Surg 2008;48:1108–13. small abdominal aortic aneurysms correlate with clinical events. Br J Surg
17. Piechota-Polanczyk A, Jozkowicz A, Nowak W, Eilenberg W, Neu- 2010;97:37–44.
mayer C, Malinski T, et al. The Abdominal Aortic Aneurysm and Intralu-
26. Vorp DA, Lee PC, Wang DH, Makaroun MS, Nemoto EM, Ogawa S,
minal Thrombus: Current Concepts of Development and Treatment. Front
Cardiovasc Med 2015;2:19. et al. Association of intraluminal thrombus in abdominal aortic aneurysm
with local hypoxia and wall weakening. J Vasc Surg 2001;34:291–9.
18. Folkesson M, Silveira A, Eriksson P, Swedenborg J. Protease activ-
ity in the multi-layered intra-luminal thrombus of abdominal aortic aneu- 27. Vorp DA, Federspiel WJ, Webster MW. Does laminated intraluminal
rysms. Atherosclerosis 2011;218:294–9. thrombus within abdominal aortic aneurysm cause anoxia of the aortic
wall? J Vasc Surg 1996;23:540–1.
19. Mower WR, Quiñones WJ, Gambhir SS. Effect of intraluminal
thrombus on abdominal aortic aneurysm wall stress. J Vasc Surg 1997;26: 28. Thubrikar MJ, Robicsek F, Labrosse M, Chervenkoff V, Fowler BL.
602–8. Effect of thrombus on abdominal aortic aneurysm wall dilation and stress.
J Cardiovasc Surg (Torino) 2003;44:67–77.
20. Wang DH, Makaroun MS, Webster MW, Vorp DA. Effect of intra-
luminal thrombus on wall stress in patient-specific models of abdominal 29. Georgakarakos E, Ioannou CV, Volanis S, Papaharilaou Y, Ekateri-
aortic aneurysm. J Vasc Surg 2002;36:598–604. naris J, Katsamouris AN. The influence of intraluminal thrombus on ab-
21. Liu O, Jia L, Liu X, Wang Y, Wang X, Qin Y, et al. Clopidogrel, a dominal aortic aneurysm wall stress. Int Angiol 2009;28:325–33.
platelet P2Y12 receptor inhibitor, reduces vascular inflammation and an- 30. Polzer S, Gasser TC, Bursa J, Staffa R, Vlachovsky R, Man V, et al.
giotensin II induced-abdominal aortic aneurysm progression. PLoS One Importance of material model in wall stress prediction in abdominal aortic
2012;7:e51707. aneurysms. Med Eng Phys 2013;35:1282–9.
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.