bs_bs_banner

738 K Tanaka et al.

5 Balchin I, Whittaker JC, Lamont RF, Steer PJ. Maternal and fetal
characteristics associated with meconium-stained amniotic fluid.
Obstet. Gynecol. 2011; 117: 828–35.
6 Tyler DC, Murphy J, Cheney FW. Mechanical and chemical damage
to lung tissue caused by meconium aspiration. Pediatrics 1978; 62:
454–9.
7 Dargaville PA, South M, McDougall PN. Surfactant and surfactant
inhibitors in meconium aspiration syndrome. J. Pediatr. 2001; 138:
113–15.
8 Chen CT, Toung TJ, Rogers MC. Effect of intra-alveolar meconium
on pulmonary surface tension properties. Crit. Care Med. 1985; 13:
233–6.

Successful treatment by coil embolization for infantile hemangioma

with Kasabach–Meritt syndrome of newborn

Mari Tezuka,1 Masaaki Ohta,3 Fumihiro Ochi,2 Toshiyuki Chisaka,3 Takashi Higaki3 and Eiichi Ishii3
1
Division of Pediatrics, Ehime Prefectural Central Hospital, Matsuyama, 2Division of Pediatrics, Yawatahama City General
Hospital, Yawatahama and 3Department of Pediatrics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan

Abstract Infantile hemangioma (IH) is the most common tumor of infancy, and it sometimes associated with Kasabach–Meritt
syndrome (KMS) characterized by anemia, intraperitoneal hemorrhage secondary to rupture, coagulopathy, jaundice,
and vascular malformations involving the brain, skin, gut, and other organs. Here, we report two newborn patients having
IH with KMS at birth. The first patient had a giant hemangioma in the liver, which was successfully treated with i.v.
corticosteroid and coil embolization. The second patient had a large hemangioma of the right axillary region, which was
also successfully treated with i.v. corticosteroid, beta-blocker, coil embolization and local irradiation. All symptoms were
controlled without any side-effects in both patients. According to these findings, combination therapy including coil
embolization and corticosteroid is effective for IH patients with KMS. The indications for and timing of coil
embolization should be determined further cases have been accumulated.

Key words coil embolization, corticosteroid, infantile hemangioma, Kasabach–Meritt syndrome.

Infantile hemangioma (IH), a benign vascular tumor, is the most
common tumor of infancy, occurring in 5% of all newborns.1 IH
has been sometimes associated with Kasabach–Meritt syndrome
(KMS), characterized by anemia, intraperitoneal hemorrhage
secondary to rupture, consumptive coagulopathy, obstructive
jaundice, and vascular malformations involving the brain, skin,
gut, and other organs. The incidence of KMS in infants with huge
hemangioma is approximately 0.3% of births, and the mortality
rate exceeds 30%.2 Isaacs reported that the fetal and neonatal
survival rates for hepatic hemangioma were 70% and 77%,
respectively.3 In his report, the cause of death was fetal hydrops,
cardiac failure due to arteriovenous shunting in the tumor, rupture
of the liver followed by fatal hemorrhage during delivery, and
thrombocytopenia from platelet trapping in the hemangioma
resulting in consumptive coagulopathy.
Here, we report the cases of two newborns with IH, who were
successfully treated with combination therapy including coil
embolization and corticosteroid.
Correspondence: Takashi Higaki, MD, Department of Pediatrics,
Ehime University Graduate School of Medicine, Shitsukawa, Toon,
Ehime 791-0295, Japan. Email: higaki@m.ehime-u.ac.jp
Received 14 August 2014; revised 20 October 2014; accepted 20
November 2014.
doi: 10.1111/ped.12618
Case reports
Case 1
A female newborn, who had been prenatally diagnosed with
vascular tumor of right liver on ultrasound, was delivered at 38
weeks’ gestational age by emergency cesarean section for pro-
gressive heart failure. Apgar score was 8/9 and bodyweight was
2314 g at birth. Physical examination showed tachypnea (160/
min), cyanosis (PaO2 90%), hypotension (55/25 mmHg), and
abdominal vascular murmur (Levine 5/6). No other detectable
hemangioma was observed in this patient. On chest radiography
cardiothoracic ratio was increased at 80% (Fig. 1a), and contrast-
enhanced computed tomography showed a large liver tumor
(Fig. 1b). Ultrasonography showed a large mass in the right liver
lobe, 5.5 cm × 5.0 cm in size, with the appearance of cavernous
hemangioma (Fig. 1e). Laboratory examination showed no
thrombocytopenia, but low fibrinogen (71 mg/dL; normal, 200–
400 mg/dL), high fibrin degradation product (FDP; 22.6 μg/mL;
normal, <5.0 μg/mL) and d-dimer (7.2 μg/mL; normal,
<1.0 μg/mL).
Congestive heart failure gradually developed and assisted
mechanical ventilation was started at several hours after birth. In
addition, i.v. corticosteroids (methylprednisone 20 mg/kg/day for
first 3 days, and then 10 and 5 mg/kg/day for the next 2 days,
followed by 2.5 mg/kg/day for the last 8 days), diuretics, and

© 2015 Japan Pediatric Society

 Coil embolization for IH 739

Fig. 1 Patient 1. (a) Chest radiography at birth showing prominent cardiomegaly. (b) Contrast-enhanced computed tomography at birth
showing a large liver hemangioma. (c) Angiography and (e) ultrasonography before coil embolization show enriched blood vessels in
hemangioma, but (d,f) reduced blood flow after embolization.

© 2015 Japan Pediatric Society

740 M Tezuka et al.
dopamine (5 μg/kg/min) were prescribed. Tumor size slightly
decreased on this treatment, whereas clinical condition gradually
deteriorated and platelet count decreased to 82 000/μL, probably
due to KMS. Given that tumor resection was difficult because of
the large tumor size and the presence of direct feeding from the
celiac artery, coil embolization of the liver hemangioma was
performed on day 8 after birth.
Under general anesthesia, the celiac artery and the inferior
phrenic artery feeders supplying the tumor were embolized by
coils (InterlockFibered IDC Occlusion System; Boston Scien-
tific, Natick, MA, USA; 0.014 inch Tornado embolization coil;
Cook Medical, Bloomington, IN, USA) via the right femoral
artery approach. Angiography and ultrasonography after coil
embolization showed loss of blood flow to the liver hemangioma
(Fig. 1d,f). After the coil embolization, clinical condition
Fig. 2 Patient 2. (a) Large hemangioma of the right axillary region observed at birth. (b) Biopsy specimen showing oval-shaped lobules
composed of capillaries with obstructed lumina (HE). (c) Angiography before treatment showing enriched blood vessels in the hemangioma,
but (d) loss of blood flow after embolization.
© 2015 Japan Pediatric Society
immediately improved, and mechanical ventilation was discon-
tinued on day 3 after the embolization. The size of the
hemangioma gradually decreased, due to the blood flow reduc-
tion, and the congestive heart failure improved. All symptoms
have been controlled for 9 months in this patient.
Case 2
A boy was delivered at 39 weeks 5 days’ gestational age. Apgar
score was 9/9 and bodyweight was 3200 g at birth. The patient
was referred to Ehime University hospital on day 8 after birth,
due to soft-tissue tumor of the right axillary region (Fig. 2a).
Laboratory examination showed thrombocytopenia (platelets, 6.4
× 104/μL) and coagulopathy (FDP, 34.0 μg/mL; normal, <5.0 μg/
mL; d-dimer, 28.4 μg/mL; normal, <1.0 μg/mL), compatible
with KMS. Contrast-enhanced computed tomography showed a

large tumor, 6.0 cm × 5.0 cm in size, with the appearance of
cavernous hemangioma. Biopsy of the hemangioma showed
tufted angioma (Fig. 2b).
Congestive heart failure and severe decompensated
coagulopathy developed, and the patient was treated with i.v.
corticosteroids (prednisone 2.3–3.0 mg/kg/day) and diuretics.
Clinical condition improved initially but then deteriorated. With
additional oral beta-blocker (0.5–2 mg/kg/day), the clinical con-
dition improved again before further deterioration. On day 76
after birth, emergency coil embolization was performed for
hemangioma. Under general anesthesia, the right subclavian
artery feeders supplying the tumor were embolized using coils
(Orbit Galaxy Detachable Coil System; Codman Neuro,
Raynham, MA, USA). Angiography performed after coil
embolization showed loss of blood flow to the hemangioma.
After the coil embolization, platelet count was initially raised,
but then decreased. Therefore, radiation therapy with a total dose
of 10 Gy (10 fractions of 1 Gy) was performed for the
hemangioma. All symptoms have been controlled for 14 months
in this patient.
Discussion
Infantile hemangioma is formed from a complex mixture of
clonal endothelial cells associated with pericytes, dendritic cells,
and mast cells. IH is sometimes associated with KMS, which
will induce severe conditions such as tumor rupture or
coagulopathy, but no standard therapy has been established for
IH with KMS.
Medical therapy for IH includes corticosteroids, propranolol,
vincristine, α-interferon, interventional modalities, surgical
resection, or orthotopic liver transplantation. Corticosteroid
therapy is the first step in the treatment of IH. The precise mecha-
nism of corticosteroid is unclear. Greenberger et al. reported that
dexamethasone inhibited the vasculogenic potential of stem cells
derived from human IH in a murine model.4 Corticosteroid also
inhibited the expression of vascular endothelial growth factor
(VEGF)-A by hemangioma-derived stem cells, and silencing of
VEGF-A expression in these cells inhibited vasculogenesis in
vivo.4 A response to corticosteroids can be achieved within 1–3
weeks, and the success rate varies from 20% to 70% for infantile
hepatic hemangioma.5 Regulation of hemangioma growth and
involution is important but poorly understood. Basic fibroblast
growth factors and VEGF are two major pro-angiogenic factors.
Apoptosis has been shown during the involution phase. It has
been suggested that this effect is due to decreasing arterial flow
and signaling via β-receptors, causing endothelial cell apoptosis
and inhibition of angiogenesis.6,7
Interventional therapy such as coil embolization and
embolization of an Amplatzer vascular plug (AGA Medical,
Coil embolization for IH 741
Golden Valley, MN, USA) has been reported to be effective for
the treatment of infantile liver hemangioma.8,9 Careful observa-
tion is needed, however, because of the high risk of puncturing
the artery during catheter treatment, especially in neonates. To
avoid such accidents, it is important to use thin sheaths (e.g. 4 Fr)
and ensure careful hemostasis.
The problems of interventional therapy include thrombosis by
polyvinyl alcohol,10 and development of collateral circulation
after coil embolization.8
The appropriate timing of coil embolization for IH is still
undetermined. Coil embolization at the early stage can reduce the
blood flow of the feeding artery in hemangioma.8 In the present
patients, we used coil embolization for IH within 4 weeks after
birth, resulting in tumor reduction in both patients. Coil
embolization soon after birth could delay the requirement for
surgery and is intended to improve prognosis in patients with
heart failure due to hemangioma.
Conclusion
Combination therapy including coil embolization and
corticosteroid is effective for IH patients with KMS. The indica-
tions for and timing of coil embolization need to be determined
on further accumulation of cases.
References
1 Klicine C, Freden IJ. Infantile hemangiomas: How common are
they? A systematic review of the medical literature. Pediatr.
Dermatol. 2008; 25: 168–73.
2 Hall GW. Kasabach-Meritt syndrome: Pathogenesis and manage-
ment. Br. J. Haematol. 2001; 112: 851–62.
3 Isaacs H Jr. Fetal and neonatal hepatic tumors. J. Pediatr. Surg.
2007; 42: 1797–803.
4 Greenberger S, Boscolo E, Adini I, Mulliken JB, Bischoff J.
Corticosteroid suppression of V EGF-A in infantile hemangioma-
derived stem cells. N. Engl. J. Med. 2010; 362: 1005–13.
5 Davenport M, Hansen L, Heaton ND, Howard ER.
Haemangioendothelioma of the liver in infants. J. Pediatr. Surg.
1995; 30: 44–8.
6 Storch CH, Hoeger PH. Propranolol for infantile haemangiomas:
Insights into the molecular mechanisms of action. Br. J. Dermatol.
2010; 163: 269–74.
7 Smith SKS, Smith DM. Beta blockade induces apoptosis in cul-
tured capillary endothelial cells. In Vitro Cell. Dev. Biol. Anim.
2002; 38: 298–304.
8 Warmann S, Bertram H, Kardorff R, Haudolf G, Fuchs J.
Interventional treatment of infantile hepatic hemangioen-
dothelioma. J. Pediatr. Surg. 2003; 38: 1177–81.
9 Kretschmar O, Knirsch W, Bernet V. Interventional treatment of a
symptomatic neonatal hepatic cavernous hemangioma using the
Amplatzer vascular plug. Cardiovasc. Intervent. Radiol. 2008; 31:
411–14.
10 Repa I, Moradian GP, Dehner LP et al. Mortalities associated with
use of a commercial suspension of polyvinyl alcohol. Radiology
1989; 170: 395–9.
© 2015 Japan Pediatric Society