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Clinical Case Report

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The resolution of carotid arterial thrombus by oral
anticoagulation after IV thrombolysis for
chemotherapy-induced stroke
A case report
∗

Bo-Chang Wu, MDa, Ming-Hung Hu, MDb,c, Vinchi Wang, MD, PhDa,d,e,

Abstract
Rationale: Cancer-related stroke has been regarded as an emerging subtype of ischemic event. Acute treatment for this subtype

may include the antiplatelet agents, anticoagulants, or endovascular intervention.
Patient concerns: A 63-year-old woman with sudden-onset right hemiparesis and conscious change was sent to our emergency
department. The patient had underlying sigmoid adenocarcinoma and received chemotherapy FOLFIRI (FOL, folinic acid; F,
fluorouracil; and IRI, irinotecan) with targeted therapy cetuximab following lower anterior resection since the diagnosis was made.
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Diagnoses: Brain magnetic resonance angiography revealed a filling defect in left carotid bulb, and neurosonography showed a
thick atherosclerotic plaque (size 4.9 mm) in the left internal carotid artery on day 5 after the onset of stroke.
Interventions: During the first three hours after onset, administration of IV tissue plasminogen activator did not resolve the
thrombus. Dabigatran (110 mg bid) started on day 7.
Outcomes: The atherosclerotic plaque dissolved on day 24. The patient recovered her muscle strength but still had nonfluent

speech in mild extent.
Lessons: Thrombolytic and anticoagulant medications in this patient suggested the thrombus formation with fibrin-rich content
which may be attributable to both cancer and chemotherapy. Dabigatran, an oral anticoagulant, had a benefit for this subtype of
ischemic stroke among patients with cancer.
Abbreviations: ATE = arterial thromboembolism, ICA = internal carotid artery, tPA = tissue plasminogen activator.
Keywords: arterial thromboembolism, dabigatran, thrombolysis, tissue plasminogen activator

and the 3rd most common cause of death in Taiwan,[1] and is still
ranked the 2nd leading cause of death worldwide, despite the
decline in the United States in the past decade.[2] It is already
known that early reperfusion therapy for acute ischemic stroke
after administration by tissue plasminogen activator (tPA) has a
better prognosis and is the mainstay of treatment for those
without contraindications.
Cancer-related stroke has been regarded as an emerging
subtype of ischemic event.[3] Here, we report the case of a
63-year-old female patient with cancer with acute cerebral
arterial embolism, in which the thrombus in the carotid bulb did
not dissolve after tPA but did so later after dabigatran. There
have been several case reports describing thrombus resolution
after dabigatran, which acts as an anticoagulant by directly
inhibiting thrombin.[4–6] We will discuss some interesting issues
regarding the pathogenesis and pharmacologic effects.

1. Introduction
Stroke may be a critical complication among patients with
cancer, regardless of venous occlusion or arterial ischemia. It has
been regarded as the most common cause of complex disability
Editor: Maya Saranathan.
Written informed consent was obtained from the patient for publication of this
case report and accompanying images.
The authors have no funding and conflicts of interest to disclose.
Data sharing not applicable to this article as no datasets were generated or
analyzed during the current study.
a
School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei
City, b Division of Hematology and Oncology, Department of Medicine, Taipei
Municipal Wangfang Hospital, c Taipei Cancer Center, Taipei Medical University,
Taipei, d Department of Neurology, Cardinal Tien Hospital, e Medical Quality
Management Center, Cardinal Tien Hospital, New Taipei City, Taiwan.
∗

Correspondence: Vinchi Wang, Department of Neurology, Cardinal Tien
Hospital, 362, Zhongzheng Road, Xindian District, New Taipei City 231, Taiwan
(e-mail: vwneur@yahoo.com.tw).

2. Case presentation

Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open access article distributed under the Creative Commons
Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

A 63-year-old woman presented to our emergency department
with sudden-onset right hemiparesis and consciousness change.
The patient got a diagnosis of sigmoid adenocarcinoma
(pT3N1aM1, p-stage IV) 4 months before this stroke, and she
had been on chemotherapy FOLFIRI (FOL, folinic acid; F,
fluorouracil; and IRI, irinotecan) with targeting agent cetuximab
as systemic therapy after lower anterior resection. Her last
FOLFIRI chemotherapy (5th cycle) with cetuximab had been
administered 4 days prior.

How to cite this article: Wu BC, Hu MH, Wang V. The resolution of carotid
arterial thrombus by oral anticoagulation after IV thrombolysis for chemotherapyinduced stroke: A case report. Medicine 2020;99:35(e21922).
Received: 13 March 2020 / Received in final form: 1 July 2020 / Accepted: 28
July 2020
http://dx.doi.org/10.1097/MD.0000000000021922

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Wu et al. Medicine (2020) 99:35

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Figure 1. A filling defect (arrow) in left carotid bulb region by magnetic
resonance angiography.

Figure 2. A thick thrombus (49 mm in size) in left carotid bulb on day 5 by
neurosonography.

chemotherapy Tegafur (5-FU) and remained stable for the
following 18 months. There was no new episode of stroke during
the follow-up period.

Sudden conscious change and fall took place 1 hour before
arrival at our emergency room. Upon arrival, she was alert,
normal vital signs, and the neurologic examination revealed
right-sided limb weakness with speech problems. She exhibited
nonfluent speech output, incorrect naming, word substitution,
but intact repetition, fair comprehension, and obedience on
secondary commands. The initial National Institute of Health
Stroke Scale scored 6 out of 42. Brain computed tomography
excluded intracranial hemorrhage, and then IV bolus of tPA (35
mg, 0.7 mg/kg) was administered soon. Mechanical thrombectomy was deferred because of her weak physical condition after
the recent chemotherapy course. Echocardiography did not
reveal any intracardiac thrombus. Brain magnetic resonance
imaging showed acute infarction in left middle cerebral artery
territory, mainly involving left insula and parietal lobe, and
magnetic resonance angiography revealed a vague plaque image
in left internal carotid artery (ICA) of the neck and occlusion of
the Sylvian and cortical M3 segment of left middle cerebral artery
(Fig. 1). Coagulation studies showed normal partial thrombin
time, prothrombin time, fibrinogen, and antithrombin III, but
elevated D-Dimer 1152 mg/mL. All other laboratory studies were
within normal limits, including tumor marker CEA 1.19 ng/mL
and CA-199 11.92 IU/mL. Her motor aphasia persisted, but her
weakness improved during her stay in the ICU on the 2nd day.
On day 5 after the onset of stroke, neurosonography revealed a
thick atherosclerotic plaque in left carotid bulb (Fig. 2). On day 7,
she started dabigatran (110 mg twice daily) due to suspicion of
cerebral embolism possibly caused by ICA plaque rupture. The
plaque image by the follow-up neurosonography still existed on
day 10, but disappeared on day 24 (Fig. 3), that is, 17 days after
the use of dabigatran. During these 17 days, dabigatran was the
only treatment administered. The patient left the hospital with
mild motor dysphasia but no motor weakness. After discharge,
the patient was on dabigatran for 3 months, and then aspirin to
prevent thrombus formation. Besides, she continued oral

3. Discussion
We cast interest on this case because of the finding of atheroma by
magnetic resonance angiography and neurosonography, and of

Figure 3. The thrombus dissolved on day 24 by the follow-up neurosonography.

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Thrombi can be classified as white or red thrombi based on
their macroscopic appearance and predominant color. Several
different descriptions of red and white thrombi have been
published. Koupenova et al described white thrombus as a
platelet-rich thrombus formed in arteries, and red thrombus as a
fibrin- and erythrocyte-rich thrombus formed in veins due to
different velocities in arteries and veins.[11] In contrast, there are
few reports of fibrin-rich thrombosis in arteries.[12,13] According
to Quadros et al, white thrombi have a higher percentage of fibrin
but a lower percentage of erythrocytes than red thrombi.[14]
White thrombi are smaller and mainly composed of fibrin.
Maekawa et al reported that cardioembolic thrombi have a
higher percentage of fibrin and fewer erythrocytes than noncardioembolic thrombi.[15] Therefore, white thrombi may be
either platelet rich or fibrin rich, whereas red thrombi contain
erythrocytes.
We did not obtain the thrombus sample for pathologic
diagnosis from this patient. Nevertheless, based on the fact that
the thrombus disappeared after dabigatran administration, we
thought that a fibrin- and erythrocyte-rich red thrombus was
more likely than a platelet-rich white one in our case. According
to Maekawa et al, a higher percentage of erythrocytes was more
common in a noncardioembolic thrombus,[15] which was
consistent with the left ICA thrombus in our case. Dabigatran
would resolve the plaque indirectly by limiting the extension of
the existing thrombus, making it easier to be removed by plasmin.
Another interesting issue is whether chemotherapy or cancer
itself caused thrombus formation. Navi et al compared the
incidences of arterial thromboembolisms (ATEs) (such as stroke
and myocardial infarction) in patients with cancer at different
sites and among those with advanced stages.[16] It is known that
the risk of ATEs is higher in lung, colorectal, and gastric cancers.
Advanced stages further increase the risk, and the risk of ischemic
stroke is highest within the first 6 months after the diagnosis of
cancer. The cumulative incidences of myocardial infarction and
ischemic stroke since the diagnosis of colorectal cancer have been
reported. Six-month hazard ratios of myocardial and cerebral
ischemia among newly diagnosed patients with cancer were
estimated to be 2.9 and 1.9, respectively.[16] It seems that
intensive chemotherapy after diagnosis might be associated with
this increased risk, as in our case.
The multifactorial pathogenesis of ATEs in cancers may
include individual cardiovascular risks, comorbidities, immobilization, primary cancer location, and treatment by chemotherapy
or radiotherapy.[17] Cancer can activate platelets, increase
expression of procoagulants, and suppress fibrinolytic activity.[18–20] Activation of these procoagulant factors can take place
during the apoptosis of tumor cells induced by chemotherapy or
radiation.[17] Both chemotherapy and radiotherapy cause
endothelium damage, which induces the activation of platelets
and the coagulation cascade. In addition, a reduction in
fibrinolysis is involved in tumor growth and metastasis.
Furthermore, 5-fluorouracil, a pyrimidine analogue used in the
treatment of colorectal cancer, may cause direct endothelial
damage leading to platelet and coagulation cascade activation.[17]
In this patient with colorectal cancer, it was unlikely that the
stroke was the result of metastasis or arterial invasion of tumor
growth based on the evidence that dabigatran resolved the
thrombus. Both cancer itself and chemotherapy give rise to a
hypercoagulable state; therefore, it is difficult to say which one
induced the thrombus. However, we figured that chemotherapy

Table 1
Thrombus resolution after dabigatran use, listing the thrombus
location, dabigatran doses, and total treatment days of dabigatran
before the thrombus disappearance first noted in our and previous
reports.

Kaku[4]
Nagamoto et al[5]
Akiyama et al[6]
This report

Thrombus
location

Dabigatran
doses

Days after dabigatran use
till the thrombus disappeared

Intracardiac
Intracardiac
Carotid
Carotid

150 mg bid
110 mg bid
110 mg bid
110 mg bid

21 d
27 d
16 d
17 d

bid = twice daily.

the atheroma resolving after the use of dabigatran. Someone may
question clinical issues about this case, including why the
intravenous thrombolysis by tPA failed but later atheroma
resolved by dabigatran; why the atheroma formed in the artery
rather than vein; and whether the atheroma formation caused by
cancer itself or by chemotherapy.
The tPA, a serine protease found on the endothelial lining of
blood vessels, binds to fibrin and facilitates plasminogen
conversion to plasmin, which then breaks down the thrombus.[7]
The efficacy of recanalization by tPA may be related to the
location and burden of the thrombus, as the thrombus in the
proximal ICA is more resistant to tPA than distal ones.[8] In our
case, we also postulate that tPA did have some subtle effect on the
thrombus that made the latter medication – dabigatran resolve
this atheroma efficiently. There have been several reports of
similar resolution of intravascular and intracardiac thrombi by
dabigatran. Kaku reported a case of intracardiac thrombus
resolution after anticoagulation therapy with dabigatran (150 mg
twice daily).[4] Nagamoto et al reported an example that
dabigatran (110 mg twice daily) resolved a left ventricular
thrombus.[5] Akiyama et al described the thrombolytic action of
dabigatran (110 mg twice daily) on an ICA thrombus.[6] Kaku
and Nagamoto et al reported cases with the resolution of
intracardiac thrombi, whereas Akiyama et al reported a carotid
thrombus. The intracardiac thrombus dissolved completely in 21
and 27 days in Kaku’s and Nagamoto’s cases, respectively
(Table 1). The patient in the report by Akiyama et al took
irregular dosing of dabigatran 110 mg bid for approximately 3
years. A carotid thrombus was incidentally found by the neck
vessel sonographic examination performed for cancer staging,
without mentioning the thrombus size. Regular use of dabigatran
began in that case, and the carotid thrombus disappeared in 16
days. There are some similarities between our and Akiyama’s
cases, including the thrombus location (both were within ICA
near carotid bulb), the dose of dabigatran (both were 110 mg
twice daily), and history of cancer (stage III esophageal
carcinoma in Akiyama’s patient and stage IV colorectal
carcinoma in ours). All of the above case reports did not
mention the use of tPA for their patients. Dabigatran was the only
treatment for the thrombus.
Dabigatran, a direct oral anticoagulant, directly binds to
thrombin. Without the activation of thrombin, the drug blocks
the transformation of fibrinogen into fibrin, resulting in no new
thrombus formation.[9] Besides its primary action of anticoagulation, its contribution to thrombolysis is postulated to
be the inhibition of thrombus extension, which in turn causes
unstable fibrin networks to be broken down by plasmin.[10]
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subtype of ischemic stroke with unique pathomechanisms. J Stroke
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[4] Kaku B. Intra-cardiac thrombus resolution after anti-coagulation
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[5] Nagamoto Y, Shiomi T, Matsuura T, et al. Resolution of a left ventricular
thrombus by the thrombolytic action of dabigatran. Heart Vessels
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[6] Akiyama H, Hoshino M, Shimizu T, et al. Resolution of internal carotid
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[7] Bivard A, Lin L, Parsonsb MW. Review of stroke thrombolytics. J Stroke
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[10] Kato T, Yasaka M, Yabuki T, et al. Two-week administration of
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was the primary factor in thrombus formation because the onset
of stroke was within a short period after the chemotherapy
courses. We did not perform IA thrombectomy for this patient. If
we did, the content of thrombus by pathologic analysis, plateletor fibrin-rich, would cast more interest in the pathogenesis of the
thrombus.
Thus, in our case, we hypothesized a “two-step” mechanism in
this cancer-related stroke. First, the cancer made an environment
with higher procoagulants predisposing the patient to thrombus
formation. Second, on the following adjuvant chemotherapy,
accelerated thrombus formation by damaging the endothelium
and inducing the coagulation cascade occurred. Given that our
patient developed stroke after several cycles of chemotherapy, the
diagnosis of chemotherapy-induced stroke was reasonable as
these events occurred chronologically. We also observed the
thrombus resolution effect of dabigatran, which could be
explained as stated in this article. In this stroke patient with
colon cancer, thrombus formed in a “two-step” mechanism,
which was later resolved by an oral anticoagulant. Oral
anticoagulation had benefit for this subtype of ischemic stroke.
Thrombolytic and anticoagulant medications in this patient
suggested the thrombus formation with fibrin-rich content which
may be attributable to both cancer and chemotherapy.

Acknowledgment
The authors thank Editage-Taiwan (#VIANG_4) for providing
this editing service.

Author contributions
Bo-Chang Wu: review of the medical history; literature search;
manuscript drafting.
Ming-Hung Hu: cancer history review; consultation of medication effects.
Vinchi Wang: stroke patient care; draft review and discussion;
literature search.

References
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J Stroke 2014;16:59–64.
[2] Guzik A, Bushnell C. Stroke epidemiology and risk factor management.
Continuum (Minneap Minn) 2017;23:15–39.

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