Case Reports
Published online: October 27, 2005

Cerebrovasc Dis 2005;20:475–478
DOI: 10.1159/000089335

Brain Embolism Caused by a Mobile Aortic
Thrombus with Iron Deficiency Anemia
Yusuke Yakushiji a, Yasukazu Terasaki a, Ryoichi Otsubo a,
Masahiro Yasaka a, Hiroshi Oe a, Naoaki Yamada c,
Kazuhiro Nishigami b, Hiroaki Naritomi a, Kazuo Minematsu a
a

Cerebrovascular and b Cardiovascular Divisions,
Department of Medicine, and c Department of Radiology,
National Cardiovascular Center, Osaka, Japan

Atherosclerotic lesions at the aortic arch are recognized as potential sources of embolic stroke [1]. There were some reports of
embolic stroke caused by a mobile thrombus located at the aortic
arch (MTAA) [2–5]. Although almost all these patients had marked
atherosclerotic changes, a few reports demonstrated that an MTAA
was not accompanied by atherosclerotic changes and had no definite etiology [4, 5]. Furthermore, previous studies suggested an association between thrombogenesis and anemia [6, 7]. We report 2
female patients with iron deficiency anemia (IDA) who developed
brain embolisms caused by an MTAA without having atherosclerotic changes in the aortic arch.
Report of 2 Cases
Patient 1. A 50-year-old housewife was admitted to our hospital
because she abruptly developed a disturbance of consciousness. She
had suffered from anorexia since the age of 17 years and from occasional hematochezia for 2 months before the admission. The patient had no established risk factors associated with cardiovascular
diseases except for smoking. Her family history was not particular.
On physical examination, she was emaciated (body mass index
15.2) and pale. Her pulse was regular (80/min), and the blood pressure was 120/70 mm Hg. There were systolic cardiac murmurs and
no carotid bruits. Neurological examinations revealed that she was
drowsy and had aphasia and a right-sided hemiplegia. Laboratory
examinations (table 1) demonstrated severe IDA, mild thrombocytosis, a hypercoagulable state and a low plasma level of protein S
activity (PSA). Her parents’ PSAs were normal.
On the day of admission (day 1), brain diffusion-weighted imaging showed an acute infarction in the left middle cerebral artery
area (fig. 1a). On magnetic resonance angiography (MRA), the left
internal carotid artery was occluded. There was no evidence of atheromatous changes in intracranial or extracranial arteries on carotid ultrasonography or MRA. Transesophageal echocardiography
(TEE) demonstrated a mobile mass (18 mm ! 8 mm) in the aortic
arch (fig. 1b). Although the attachment of the mobile mass could
not be evaluated by TEE, no other abnormalities, such as atherosclerotic changes, could be detected on TEE. Thoracic cine-mag-

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netic resonance imaging (CMRI) revealed a club-shaped floating
mass (fig. 1c), which was attached to the wall of the ascending aorta, but there were no abnormalities on the internal surface of the
aorta, including the attachment of the mass. Extensive examinations were made to search for a cause of the IDA, but no abnormality was detected except for internal hemorrhoids. Her IDA improved with blood transfusion, and heparin administration was
started. On day 19, the mass was no longer detected on TEE and
CMRI. The plasma levels of thrombin-antithrombin III complex
and D-dimer normalized.
The patient’s hospital course was uneventful. She became used
to walk with a cane. She was discharged from hospital on warfarin
therapy. One year after the stroke, warfarin sodium was switched
to aspirin. Reexamination of her PSA showed it improved to the
normal range (76%). During 2 years of follow-up, the patient had
no recurrence of stroke, thrombophilia or IDA.
Patient 2. A 41-year-old housewife was admitted because of sudden onset of dysarthria and right-sided hemiplegia. Her medical
history included epimenorrhagia since the age of 20 years. The patient had no established risk factors associated with cardiovascular
diseases except for smoking. Her uncle had an ischemic stroke. On
physical examination, her body mass index was 24, the pulse was
regular (64/min), and the blood pressure was 128/64 mm Hg. Her
palpebral conjunctiva was pale, suggesting anemia. She had mild

Table 1. Laboratory data of the two patients

RBC count ! 10,000/␮l
Hemoglobin, g/dl
Hematocrit, %
MCV, ␮m3
MCH, pg
Platelet count ! 10,000/␮l
Reticulocytes, ‰
Fe, ␮g/dl
Ferritin, ␮g/ml
TAT, ␮g/ml
D-dimer, ␮g/ml
Protein S activity, %
CRP, mg/dl

Normal
range

Patient 1 Patient 2

380–510
12.0–16.5
35–45
85–100
27–33
15.0–35.0
5–20
43–172
0–429
<2.00
<1.0
65–105
<0.6

333
5.5
20
62
16.7
42.0
10
16
21
6.08
5.2
36
0.09

401
7.9
25
61
18.9
36.0
23
9
2
3.62
1.2
54
0.05

RBC = Red blood cells; MCV = mean corpuscular volume;
MCH = mean corpuscular hemoglobin; TAT = thrombin-antithrombin complex; CRP = C-reactive protein.

Fig. 1. Diagnostic images of patient 1. a Brain diffusion-weighted imaging shows an acute infarcted lesion in the left middle
cerebral artery area. b Transesophageal echocardiography reveals a mobile mass and no atherosclerotic lesion in the aortic
arch. c Thoracic cine-magnetic resonance imaging reveals a
floating mass attached in the aortic arch.

systolic cardiac murmurs and no carotid bruits. Neurological examinations revealed dysarthria and a right-sided hemiplegia. Laboratory examinations (table 1) demonstrated IDA, mild thrombocytosis, a hypercoagulable state and a low plasma PSA level. Her
parents’ PSAs were not measured.
On the day of admission (day 1), brain diffusion-weighted imaging showed acute infarctions in the bilateral cerebellum and the
territories of the left middle cerebral artery and the left anterior
cerebral artery (fig. 2a). MRA demonstrated a left anterior cerebral
artery occlusion. There was no evidence of atheromatous changes
in intracranial or extracranial arteries on carotid ultrasonography
or MRA. TEE revealed a mobile mass (5 mm ! 10 mm) in the
aortic arch (fig. 2b). No other abnormalities, such as atherosclerosis,
were revealed in the aortic arch, including the attachment of the
mass. Heparin administration was started, and the mobile mass
could not be detected by thoracic CMRI or TEE on day 7. Tho-

476

racic CMRI also showed no abnormalities on the internal surface
of the aorta. The plasma levels of thrombin-antithrombin III complex and D-dimer normalized. Further examinations were done to
search for a cause of the IDA, and the patient was found to have
adenomyosis uteri.
A month later, the patient’s IDA was successfully treated with
ferrotherapy. With a mild right-sided hemiplegia she was discharged from hospital taking warfarin and ferrotherapy. Six months
after stroke onset, the patient had no recurrence of stroke or IDA.
Then, reexamination after switching warfarin sodium to aspirin
showed that PSA had normalized (80%).
Discussion
In the present cases, there were no causes of stroke, such as atheromatous diseases, other than a mobile mass attached to the aortic
arch. So, we considered that embolic occlusion caused by fragments

Case Reports

Fig. 2. Diagnostic images of patient 2. a Brain diffusion-weighted imaging shows acute infarcted lesions in the
territories of the left middle cerebral artery and the left anterior cerebral artery. b TEE reveals a mobile mass and
no atherosclerotic lesion in the aortic arch.

of the mass would be the most likely mechanism of their neurological events. Although it was initially difficult to determine
whether the mass was a thrombus or a tumor, the diagnosis of a
thrombus was made because the mass disappeared with anticoagulation therapy.
There were some common denominators in these cases, including middle age, female gender, no cardiovascular risk factors except
for smoking, the complication of severe IDA and a hypercoagulable
state at stroke onset, and an MTAA without atherosclerotic changes as a potential embolic source.
In previous studies, embolic stroke associated with an MTAA
usually showed atherosclerotic changes at the origin of the MTAA
[2–5]. Therefore, it seems that atherosclerosis plays a major role in
the formation of a mobile thrombus at the aortic arch. However,
in those studies, an MTAA was detected in a small number of cases without identifiable atherosclerotic changes in the aorta [4, 5].
There are scattered reports of various conditions other than atherosclerotic changes that may predispose to intra-aortic thrombosis,
such as thrombocythemia [8], polycythemia [9], antithrombin III
deficiency [10], protein C deficiency [4], antiphospholipid antibody
syndrome [4], malignant tumor [2], blunt chest trauma [11], chest
gunshot wound [12] or systemic fungal infection [13]. (However,
these abnormalities were not seen in the present cases.) Thus, factors other than severe atherosclerosis may play an alternative role
in the MTAA formation.
In the common denominators in the present cases, we considered that severe anemia was noteworthy for the MTAA formation.
There are several mechanisms that may explain the association of
thrombus formation in the aortic arch with anemia. Firstly, anemia
following acute bleeding increases platelet adhesiveness [6] and decreases fibrinolytic activity [7]. The concomitant presence of reactive thrombocytosis may have a role in inducing intravascular

Case Reports

thrombogenesis [14]. Secondly, anemia may induce a hyperkinetic
circulatory state. In the present cases, patients had cardiac systolic
murmurs. Arterial bruits are common in patients with severe anemia [15] and are a physical sign of turbulent flow due to increased
hemodynamic force. An increased hemodynamic force has been
shown to upregulate the endothelial adhesion molecule genes [16,
17], which may induce local immunologic-inflammatory reactions
leading to thrombogenesis.
It was unclear why the thrombus appeared in no other parts but
the aortic arch in our patients. Laperche et al. [4] reported that 23
patients without marked atherosclerotic changes had MTAA detected among 27,855 TEE examinations and that they did not have
any other visible sites of thrombi on TEE. So, the aortic arch may
be a part where the thrombus appears more frequently than in
other parts of the aorta.
Both presented patients had low PSA levels on admission without any concomitant conditions, such as hepatopathy, taking oral
contraceptives or warfarin, pregnancy, systemic lupus erythematosus or nephropathy. In patient 1, the low PSA level was found not
to be hereditary. In addition, both PSA levels in the present cases
normalized after anticoagulant therapy. Thus, the low PSA levels
seen after stroke onset might reflect PSA consumption due to a hypercoagulable state.
Endothelial cell adhesion, which plays one of the important
roles in thrombogenesis, could be caused by inflammation. Recently, it has been reported that human aortic endothelial cell adhesion
was induced by C-reactive protein which is a novel marker of inflammation [18]. However, C-reactive protein elevations were not
demonstrated in the current 2 cases (table 1).
In conclusion, we demonstrated 2 stroke patients in whom an
MTAA was considered as the most likely source of emboli. These
MTAAs had no relation to the atherosclerotic aorta but to severe

477

IDA. Severe IDA might be one of the factors implicated in the formation of MTAA. Therefore, if the cryptogenic stroke patient has
severe IDA, the aortic arch should be explored for a mobile thrombus.
Acknowledgement
This study was partially supported by the Japan Ministry of
Health, Labour and Welfare (15C-1).
References
1 Amarenco P, Cohen A, Tzourio C, et al: Atherosclerotic disease of the
aortic arch and the risk of ischemic stroke. N Engl J Med 1994;331:1474–
1479.
2 Farah MG, Hawawini H: Thrombus of the ascending aorta as a source of
cerebral embolism. Chest 1993;104:1604–1605.
3 Dee W, Geibel A, Kasper W, Konstantinides S, Just H: Mobile thrombi
in atherosclerotic lesions of the thoracic aorta: the diagnostic impact of
transesophageal echocardiography. Am Heart J 1993;126:707–710.
4 Laperche T, Laurian C, Roudaut R, Steg PG: Mobile thromboses of the
aortic arch without aortic debris: a transesophageal echocardiographic
finding associated with unexplained arterial embolism. Circulation 1997;
96:288–294.
5 Choukroun EM, Labrousse LM, Madonna FP, Deville C: Mobile thrombus of the thoracic aorta: diagnosis and treatment in 9 cases. Ann Vasc
Surg 2002;16:714–722.
6 Shimamoto T: The ‘emergency reaction’ in thrombogenesis and atherogenesis. Am Heart J 1963;66:572–573.
7 Turpinini R, Stefanini M: Nature and mechanism of the haemostatic
breakdown in the course of experimental haemorrhagic shock. J Clin Invest 1959;38:53–65.
8 Hino H, Terasaki T, Hashimoto Y, Hara Y, Uchino M: Cerebral infarction
associated with mobile thoracic ascending aortic thrombus in a patient with
essential thrombocythemia. Rinsho Shinkeigaku 1999;39:705–710.
9 Josephson GD, Tiefenbrun J, Harvey J: Thrombosis of the descending
thoracic aorta: a case report. Surgery 1993;114:598–600.
10 Shapiro ME, Rodvien R, Bauer KA, Salzman EW: Acute aortic thrombosis in antithrombin III deficiency. JAMA 1981;245:1759–1761.
11 Chan KL: Usefulness of transesophageal echocardiography in the diagnosis of conditions mimicking aortic dissection. Am Heart J 1991;122:495–
504.
12 Bergin PJ: Aortic thrombosis and peripheral embolization after thoracic
gunshot wound diagnosed by transesophageal echocardiography. Am
Heart J 1990;119:688–690.
13 Byard RW, Jimenez CL, Carpenter BF, Hsu E: Aspergillus-related aortic
thrombosis. CMAJ 1987;136:155–156.
14 Knizley H Jr, Noyes WD: Iron deficiency anemia, papilledema, thrombocytosis, and transient hemiparesis. Arch Intern Med 1972;129:483–486.
15 Wales RT, Martin E: Arterial bruits in anemia. Br J Med 1963; 2: 1444–
1447.
16 Nagel T, Resnick N, Atkinson WJ, Dewey CF Jr, Gimbrone MA Jr: Shear
stress selectively upregulates intercellular adhesion molecule-1 expression
in cultured human vascular endothelial cells. J Clin Invest 1994;94:885–
891.
17 Morigi M, Zoja C, Figliuzzi M, et al: Fluid shear stress modulates surface
expression of adhesion molecules by endothelial cells. Blood 1995; 85:
1696–1703.
18 Devaraj S, Kumaresan PR, Jialal I: Effect of C-reactive protein on chemokine expression in human aortic endothelial cells. J Mol Cell Cardiol 2004;
36:405–410.
Dr. Yusuke Yakushiji
Division of Neurology, Department of Internal Medicine
Saga University Faculty of Medicine, 5-1-1 Nabeshima
Saga, 849-8501 (Japan)
Tel. +81 952 34 2372, Fax +81 952 34 2017
E-Mail yakushij@tg7.so-net.ne.jp

478

Cerebrovasc Dis 2005;20:478–479
DOI: 10.1159/000089336

Hemopericardium following Intravenous
Thrombolysis for Acute Ischemic Stroke
Sarah A. Kremen, Mark N. Wu, Bruce Ovbiagele
Department of Neurology, UCLA Medical Center,
Los Angeles, Calif., USA

An 83-year-old woman with a history of hypertension and hyperlipidemia presented with acute left hemiparesis, hemisensory
deficit and hemineglect within three hours of symptom onset. On
arrival to the emergency room, she was noted to be moderately
bradycardic and hypotensive. Her hypotension and bradycardia
were attributed to her possible randomization to the active treatment arm of a prehospital neuroprotective trial involving magnesium, in which she had been enrolled [1]. Mild-to-moderate hypotension and bradycardia are known side effects of magnesium treatment. Both blood pressure and heart rate normalized after she
received intravenous fluids. Admission cardiac examination, EKG
and cardiac enzymes were normal. Head CT revealed neither hemorrhage nor early ischemic changes. The patient met all qualifying
criteria for intravenous tissue plasminogen activator (IV t-PA). Although she was of advanced age, her severe stroke and good premorbid functioning as well as studies suggesting that the risks and
benefits of intravenous t-PA in ischemic stroke patients aged 680
years, are comparable to those in younger individuals when administered according to established protocols [2–4], she was given IV
t-PA according to the NINDS protocol [5].
Initially, the patient had a good response to the t-PA with mild
improvement in function of her left hand and speech. However,
1 h and 15 min after the start of administration of t-PA, the patient
became extremely hypotensive. Aggressive fluids were administered along with calcium gluconate in order to reverse any untoward
effects of possible magnesium treatment. However, her hypotension persisted. A repeat EKG showed no signs of acute cardiac
ischemia. Dopamine and norepinephrine infusions were then started, without significant improvement of her blood pressure. Emergent bedside transthoracic echocardiogram (TTE) was performed
which showed a posterior pericardial effusion with fibrin clots and
evidence of right atrial and ventricular collapse. A second set of
cardiac enzymes ordered 3 h after the first set were normal. The
patient proceeded to enter into pulseless electrical activity and then
asystole, despite aggressive cardiopulmonary resuscitation. The
patient’s family declined autopsy.
Discussion
The risk of symptomatic intracerebral hemorrhage and systemic bleeding requiring transfusion, surgery or other aggressive management following administration of IV t-PA in ischemic stroke has
been well described [5]. However, cases of hemopericardium and
cardiac tamponade after intravenous thrombolysis for ischemic
stroke are extremely rare [6]. These complications have been more
broadly reported in the cardiac literature, in patients who received
thrombolysis after acute myocardial infarction [7], and in patients
with known pericarditis [8]. However, since the institution of IV
t-PA as a standard treatment for acute ischemic stroke in 1996,
there has only been one report describing 3 such cases [1]. This

Case Reports