Volume 20 Number 5
4. Leach JL, Wolujewicz M, Strub VM. Partially recanalized
chronic dural sinus thrombosis: findings on MR imaging, time-
of-flight MR venography, and contrast enhanced MR venogra-
phy. AJNR Am J Neuroradiol 2007; 28:782–789.
5. Takemori M, Nishimura R, Sugimura K. Magnetic resonance
imaging of uterine leiomyosarcoma. Arch Gynecol Obstet 1992;
251:215–218.
Development of Multiple Cerebral Infarcts
from Disseminated Intravascular Coagulation
after Chemoembolization of a Large
Hepatocellular Carcinoma
From: Jong Hun Kim, MD, Chi Hun Kim, MD,
Dong-Kyu Lee, MD, Gyeong-Moon Kim, MD, PhD
Department of Neurology
Samsung Medical Center
Sungkyunkwan University School of Medicine
50 Ilwon-Dong, Kangnam-Ku
Seoul, 135-710 Korea
Editor:
Most patients with tumors, especially those in advanced
stages, have abnormal laboratory findings that are sugges-
tive of hypercoagulable states (1). However, symptomatic
thrombotic events, such as ischemic strokes, occur only in
some patients with malignancy. Surgery, chemotherapy, ra-
diation therapy, or trauma can be predisposing factors for
thrombotic events (1). Transarterial chemoembolization is a
frequently used treatment for large, nonresectable hepato-
cellular carcinoma (HCC). The reported major complications
of chemoembolization include tumor rupture, duodenal per-
foration, pulmonary embolism, and liver abscess (2). Rarely,
cerebral iodized oil (Lipiodol; Guerbet, Korea) embolism
through right to left shunt can occur after the chemoem-
bolization of large HCC because a large dose of iodized oil
is needed (3). Herein, we present a case in which transar-
terial chemoembolization was a predisposing factor for
multiple embolic strokes in a patient with HCC. For this
study, the authors followed the regulations and ethical
guidelines of the World Medical Association’s declaration
of Helsinki.
A 44-year-old man who had been diagnosed with a
chronic hepatitis B virus infection visited a local hospital due
to abdominal distention. Abdominal computed tomography
(CT) revealed a large HCC with a diameter of more than 15
cm (Figure, a and b). This patient was transferred to our
hospital and scheduled to undergo chemoembolization. Ac-
cording to the laboratory test, the ␣-fetoprotein levels
(129,131.2 ␮g/L) in this patient were markedly increased.
The levels of aspartate aminotransferase (132 U/L), alanine
aminotransferase (102 U/L), and ␥-glutamyl transferase (203
U/L) were elevated. In addition, the patient’s prothrombin
time and activated partial thromboplastin time were 1.22
INR and 36.2 seconds, respectively. The patient’s laboratory
tests showed no other remarkable findings. During the pro-
cedure, an intrahepatic shunt was not detected and a mix-
ture of adriamycin (50 mg) and iodized oil (25 mL) was
injected through the right hepatic artery. The patient’s vital
DOI: DOI: 10.1016/j.jvir.2009.01.030
Letters to the Editor • 691
signs were stable during the procedure. After the procedure,
the patient showed abnormal behavior, such as repeatedly
trying to sit up even after several nurses had recommended
bed rest. There were no remarkable changes in his vital signs.
Seven hours after the procedure, he was unable to move his left
leg, which got stuck between the bed and handrail, and he
could not make eye contact with family members. Neurologic
examination revealed three components of Balint syndrome
(oculomotor apraxia, optic ataxia, and simultanagnosia) and
ideomotor apraxia (a condition in which patients cannot per-
form some actions such as shaving, waving good-bye, etc). Left
central type facial palsy was also noted, and the patient’s motor
power in his left arm and leg were of grade III and IV⫹,
respectively. The patient also had a decreased position sense on
the left side, and ataxia was seen in the left limbs. Magnetic
resonance (MR) imaging helped confirm the presence of mul-
tiple ischemic infarctions in both hemispheres of the anterior
and posterior circulation territories, but MR angiography
showed that the intra- and/or extracranial arteries were nor-
mal (Figure, c and d). Unenhanced CT showed no evidence of
iodized oil emboli. Laboratory tests performed after chemoem-
bolization showed increased levels of aspartate aminotransfer-
ase (4,891 U/L), alanine aminotransferase (2,967 U/L), alkaline
phosphatase (129 U/L), ␥-glutamyl transferase (214 U/L), and
total bilirubin (3.4 mg/dL [58 ␮mol/L]). The patient’s albumin
levels (3.4 g/dL [34 g/L]) were decreased. Coagulation test
results showed a d-dimer value of 16.68 ␮g/mL and decreased
levels of antithrombin III antigen (48%)/activity (62%), protein
C antigen (17%), and free protein S antigen (49%). The patient’s
prothrombin time and activated partial thromboplastin time
were 2.21 INR and 43.3 seconds, respectively. However, the
patient’s platelet count (149 ⫻ 109/L) and fibrinogen level (6.1
␮mol/L) were within the normal range. In addition, the levels
of blood urea nitrogen, creatinine, uric acid, and electrolytes
were also within the normal range. ␣-Fetoprotein (⬎200,000
ng/mL [⬎200,000␮g/L]) and CA125 (350.7 U/mL) levels were
increased. Cardiac embolic sources and patent foramen ovale
were not detected at transesophageal and transthoracic echo-
cardiography. We began treatment with a lactulose enema and
intravenous heparin.
The patient began to recover, and his confusion disap-
peared 3 days after the procedure. However, even in the 7
days after the stroke, three embolic signals were detected
during a 30-minute monitoring with transcranial Doppler
and the embolic signal disappeared at another follow-up
transcranial Doppler examination performed 14 days after
the event. One month later, the patient had recovered from
the Balint syndrome, weakness, sensory deficit, apraxia, and
ataxia, and no further ischemic infarctions were detected on
follow-up MR images.
We postulated that the ischemic stroke in our patient was
caused by procoagulant shedding and hepatic failure. Dur-
ing the procedure, both tumor cells and normal cells were
disrupted by these conditions, which could have led to the
release of procoagulants and cytokines into the bloodstream.
Mucin, a cancer procoagulant, or cathepsin-like cysteine
proteinase, which is also a known procoagulant, form aber-
rantly in malignant cells (1). Other unknown proteins could
act as procoagulants by interacting with platelets, endothe-
lium, or other coagulation factors. In addition, the tumor
marker CA125, which was increased in the patient’s serum,
is known to be a possible procoagulant (4). The materials
shed by cells can aggravate underlying hypercoagulable
states due to malignancies (1,5). Hepatic failure could also
cause a hypercoagulable state by inducing anticoagulant
692 • Letters to the Editor May 2009 JVIR

Figure. (a) Contrast medium– enhanced liver CT scan obtained before chemoembolization shows a huge mass that encompasses most of the
right lobe. (b) CT scan obtained after chemoembolization shows that most of the viable portion of the mass was enhanced by iodized oil. (c,d)
Diffusion-weighted MR images show that multiple embolic infarctions were dispersed throughout the right and left hemispheres. The
infarctions were also scattered in the anterior and posterior circulation territories. Some of lesions are marked by white arrows.

deficiencies. After the procedure, the serum level of the liver
enzyme bilirubin was increased, as was the level of ammo-
nia. Prothrombin time and activated partial thromboplastin
time were prolonged. Simultaneously, the serum levels of
protein C/S and antithrombin III were decreased. Conse-
quently, the decreased antithrombotic activity is thought to
have aggravated the hypercoagulable state.
This complication of chemoembolization may occur
when chemoembolization is used to treat large HCCs. How-
ever, many of these cases could be underdiagnosed as he-
patic encephalopathy and other metabolic encephalopathies.
The clinical presentation of cerebrovascular events may be
diffuse encephalopathy rather than the typical acute onset of
a focal deficit if the stroke is due to disseminated intravas-
cular coagulopathy caused by the tumor (5,6).
In chemotherapy for advanced breast cancer, the use of
low-dose warfarin can prevent thromboembolic complica-
tions (7). Similarly, in cases of large HCC or in the presence
of other significant risk factors, such as chronic disseminated
intravascular coagulopathy in the thrombotic profile or a
high CA125 titer, proper preventative measures might be
needed before chemoembolization, chemotherapy, or sur-
gery.
References
1. Falanga A, Donati MB. Pathogenesis of thrombosis in patients
with malignancy. Int J Hematol 2001; 73:137–144.
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2. Xia J, Ren Z, Ye S, et al. Study of severe and rare complications
of transarterial chemoembolization (TACE) for liver cancer. Eur J
Radiol 2006; 59:407– 412.
3. Choi CS, Kim KH, Seo GS, et al. Cerebral and pulmonary embo-
lisms after transcatheter arterial chemoembolization for hepatocel-
lular carcinoma. World J Gastroenterol 2008; 14:4834 – 4837.
4. Jovin TG, Boosupalli V, Zivkovic SA, Wechsler LR, Gebel JM.
High titers of CA-125 may be associated with recurrent ischemic
strokes in patients with cancer. Neurology 2005; 64:1944 –1945.
Letters to the Editor • 693
5. Graus F, Rogers LR, Posner JB. Cerebrovascular complications
in patients with cancer. Medicine (Baltimore) 1985; 64:16 –35.
6. Collins RC, Al-Mondhiry H, Chernik NL, Posner JB.
Neurologic manifestations of intravascular coagulation in pa-
tients with cancer: a clinicopathologic analysis of 12 cases.
Neurology 1975; 25:795– 806.
7. Levine M, Hirsh J, Gent M, et al. Double-blind randomised trial
of a very-low-dose warfarin for prevention of thromboembolism
in stage IV breast cancer. Lancet 1994; 343:886 – 889.