BACKGROUND: Although vein stenting is popular for treatment for venous thromboembolism due to mechanical compression, some cases are forced to avoid inserting align agents because of immunodeficiency. CASE PRESENTATION: An 82-year-old man with left extremity redness and swelling presented to a hospital for a medical evaluation. The patient was immunodeficient because of the adverse effects of his treatment for Castleman’s disease. A contrast-enhanced computed tomography scan revealed a venous thromboembolism in inferior vena cava and the left lower extremity. Magnetic resonance venography showed that the iliac artery was compressing the iliac vein. We were reluctant to place a stent in the iliac vein has because of the patient’s immunodeficient status. Three months of treatment using single-dose edoxaban (30 mg daily) resulted in complete resolution of the thrombus. This is the first report demonstrating that single-dose edoxaban without acute-phase parenteral anticoagulation is effective in the treatment of iliac vein compression. CONCLUSIONS: A single-dose direct oral anti-coagulant without acute-phase parenteral anticoagulation is effective for mechanical compressio

Daisuke Sueta

Eiichiro Yamamoto

Hisanori Kanazawa

Kenichi Tsujita

Koichi Kaikita

Naoya Nakashima

Seiji Hokimoto

Seiji Takashio

Shinsuke Hanatani

Sunao Kojima

Yasuhiro Izumiya

Yusuke Kanemaru

Thrombosis Journal

PubMed

Crossref

Successful treatment of deep vein thrombosis caused by iliac vein compression syndrome with a single-dose direct oral anti-coagulant

Springer - Publisher Connector

CASE REPORT Open Access
Successful treatment of deep vein
thrombosis caused by iliac vein
compression syndrome with a single-dose
direct oral anti-coagulant
Naoya Nakashima, Daisuke Sueta*, Yusuke Kanemaru, Seiji Takashio, Eiichiro Yamamoto, Shinsuke Hanatani,
Hisanori Kanazawa, Yasuhiro Izumiya, Sunao Kojima, Koichi Kaikita, Seiji Hokimoto and Kenichi Tsujita
Abstract
Background: Although vein stenting is popular for treatment for venous thromboembolism due to mechanical
compression, some cases are forced to avoid inserting align agents because of immunodeficiency.
Case presentation: An 82-year-old man with left extremity redness and swelling presented to a hospital for a
medical evaluation. The patient was immunodeficient because of the adverse effects of his treatment for
Castleman’s disease. A contrast-enhanced computed tomography scan revealed a venous thromboembolism in
inferior vena cava and the left lower extremity. Magnetic resonance venography showed that the iliac artery was
compressing the iliac vein. We were reluctant to place a stent in the iliac vein has because of the patient’s
immunodeficient status. Three months of treatment using single-dose edoxaban (30 mg daily) resulted in complete
resolution of the thrombus. This is the first report demonstrating that single-dose edoxaban without acute-phase
parenteral anticoagulation is effective in the treatment of iliac vein compression.
Conclusions: A single-dose direct oral anti-coagulant without acute-phase parenteral anticoagulation is effective for
mechanical compression
Keywords: Thromboembolism, Iliac vein compression syndrome, Direct oral anti-coagulant
Background
Vein stenting [1] is the generally accepted treatment for
venous thromboembolism (VTE) due to mechanical
compression, such as Paget-Schroetter syndrome and
iliac vein compression syndrome (IVCS). However, in
immunodeficient patients, this procedure may not be ap-
propriate. We present a case of IVCS effectively treated
only with a single-dose direct oral anticoagulant
(DOAC) without acute-phase parenteral anticoagulation.
Case presentation
An 82-year-old, nonsmoking man with no history of
VTE presented to an emergency department (ED) with a
complaint of left lower extremity redness and swelling of
3 days duration. The patient had Castleman’s disease [2, 3],
and was being treated with tocilizumab (Actemra™, Chugai
Pharmaceutical Co., Ltd.) 370 mg per 3 weeks and predoni-
solone 4 mg daily [4]. He was also taking acyclovir,
voriconazole and sulfamethoxazole-trimethoprim (Baktar
Combination Tablets™, Shionogi & Co., Ltd.) for immuno-
deficiency, a side effects of tocilizumab, in addition to
clopidogrel 75 mg daily for a history of cerebral infarction.
The serum D-dimer levels in the ED was 5.2 μg/mL, and
VTE was suspected. A contrast-enhanced computed tomog-
raphy (CT)-scan revealed prominent swelling in his left ex-
tremity and contrast deficits in the inferior vena cava (IVC)
at the level of the lower lobe of kidney (Fig. 1a) and from
the left external iliac vein (Fig. 1b) to the left superfacialis
femoral vein. There was no evidence of pulmonary embo-
lisms. The patient was diagnosed with VTE and admitted to
* Correspondence: sueta-d@kumamoto-u.ac.jp
Department of Cardiovascular Medicine, Graduate School of Medical
Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto 860-8556,
Japan
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Nakashima et al. Thrombosis Journal  (2017) 15:4 
DOI 10.1186/s12959-017-0128-2
our department. On admission, his blood pressure was 161/
95 mmHg and his heart rate was 63 beats per minute. An
arterial blood gas revealed an oxygen saturation (SaO2) of
95%. His body mass index was 23.0 kg/m2. Anticoaglation
therapy, with a DOAC, edoxaban (Lixiana® and Savaysa®,
Daiichi Sankyo, Inc.) 30 mg daily was initiated. An IVC filter
was not inserted consistent with the latest guideline [5].
Magnetic resonance venography demonstrated that the bi-
furcation of the left common iliac vein was compressed be-
tween the right common iliac artery and the fifth lumbar
vertebral body (Fig. 2), confirming a diagnosis of IVCS. A
hypercoagulability work-up revealed that protein C, protein
S, antithrombin, and antiphospholipid antibodies were
within normal limits. After 7 days, a follow-up contrast-
enhanced CT scan showed a reduction in the size of the
thrombosis (Fig. 3). The patient was permitted to discharge
to home.
Anticoagulation therapy with edoxaban was continued
for 3 months according to recent guidelines [6], and the
VTE was reevaluated. A follow-up contrast-enhanced
CT scan revealed that the thrombosis had completely
resovled (Fig. 4). Moreover serum D-dimer concentration
levels was negative. Edoxaban treatment was then discon-
tinued according to a guideline [7], his clinical symptom,
physical examination and D-dimer levels were monitored
Fig. 1 Contrast-enhanced computed tomography on the first visit. A contrast deficit in (a) the inferior vena cava at the level of kidney lower lobe
(the yellow arrow), (b) the left external iliac vein (the yellow arrow), (c) the left superficial femoral vein (the yellow arrow), (d) the left popliteal
vein (the yellow arrow)
Fig. 2 Magnetic resonance venography (T2-TRA) on the first visit. rt.
CIA; right common iliac artery, lt. CIA; left common iliac artery, lt. CIV;
left common iliac vein, *: vertebral body at fifth lumbar vertebra
Nakashima et al. Thrombosis Journal  (2017) 15:4 Page 2 of 4
every month. The patient received treatment with no
hemorrhagic complications during clinical course.
The patient gave his consent for the publication of this
study.
Discussion
In 1957, May R and Thurner J reported that 22% of 430
cadavers had stenosis of the left common iliac vein
caused by compression of the right iliac artery, with wall
thickening of the iliac vein and spur-like formation. The
authors speculated that the compressions were due to
chronic mechanical compression and out-forces from ar-
tery beats [8]. In 1967, using venography, Cockett et al.
reported that iliac vein compressions were observed in
65% of VTEs of the left iliac vein, and coined IVCS [9].
In many cases, chronic iliac vein stenosis is asymptom-
atic because of the development of collateral branches in
the pelvic cavity. The diagnosis is usually made when
there is greater than 50% stenosis of the iliac vein [10],or
over 2 mmHg of pressure gradient in the vein [11]. The
first objective in the treatment of mechanical compres-
sion is release. Some studies have reported good results
with iliac vein stenting for IVCS in both early and
chronic phases [12, 13]. Stenting are generally performed
overseas. In this case, consistent with the currrent litera-
tures, we considered iliac vein stenting, but were reluc-
tant the insert of align agents because of the patient’s
immunodeficient status.
VTEs can result from a variety of causes. Inheritaed
thrombophilia, malignant diseases [14, 15], mechanical
compression from sleeping in a vehicle after an accident
[16], lower limb operations [17, 18], and pregnancy are
all important consideration in the differential diagnosis.
In this case, thrombus formation was considered to be
due to steroid administration, in addition to iliac com-
pression, since steroid hormones have been shown to in-
crease coagulation [19, 20].
In Japan, in addition to warfarin, apixaban [21], rivar-
oxaban [22] and edoxaban [23] are approved oral anti-
coagulation agents for VTEs. The initial treatments for
VTEs by apixaban and rivaroxaban requires higher
doses, while edoxaban exerts its pharmacological effects
at the same dose. Because the patient was at an in-
creased risk of bleeding from the combined use of an
anticoagulant with his antiplatelet drug, we selected
edoxaban. A daily dose of 30 mg edoxaban was chosen
because of his low body weight (less than 60 kg).
Regimen of edoxaban in Hokusai-VTE study was an
administration of edoxaban following acute-phase paren-
teral anticoagulation [23].
There is one report of successful treatment of IVCS
with rivaroxaban (30 mg→ 15 mg daily) [24]. This case
report adds to the literature by demonstrating that
single-dose edoxaban (30 mg daily) without acute-phase
parenteral anticoagulation is also effective though long-
term follow-up is still required.
Although whether edoxaban treatment continuation
or discontinuation was questionable, steroid therapy was
already stopped, we judged that his VTE was reversible.
However we monitored his clinical symptom, physical
examination and D-dimer levels every month. A long
term observation should be mandatory.
Fig. 3 Contrast-enhanced computed tomography at 7 days after the
initiation of anticoagulation therapy. The yellow arrow indicates
reduced thrombosis
Fig. 4 Contrast-enhanced computed tomography at 3 months after the
initiation of anticoagulation therapy. The thrombosis was disappeared
completely
Nakashima et al. Thrombosis Journal  (2017) 15:4 Page 3 of 4
Conclusion
A use of single-dose DOAC is well known to be a treatment
for VTE [23]. To the best of our knowledge, this is the first
report of successful treatment for IVCS with a single-dose
DOAC without acute-phase parenteral anticoagulation.
Abbreviations
CT: Computed tomography; IVC: Inferior vena cava; IVCS: Iliac vein
compression syndrome; VTE: Venous thromboembolism
Acknowledgments
We thank all of the paramedical staff and clinical secretaries for their kind
support during this work.
Funding
None.
Availability of data and materials
Please contact author for data requests.
Authors' contributions
All authors engaged in clinical practice. All authors read and approved the
final manuscript.
Competing interests
The authors declare no conflicts of interest in association with the present study.
Consent for publication
The patient gave his consent for the publication of this study.
Ethics approval and consent to participate
Not applicable.
Received: 10 December 2016 Accepted: 18 January 2017
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http://dx.doi.org/10.1186/s12959-017-0128-2

Successful treatment of deep vein thrombosis caused by iliac vein compression syndrome with a single-dose direct oral anti-coagulant

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