Splenic Hemangioma With Thrombocytopenia in a Newborn

(1)

Splenic

Hemangioma

With Thrombocytopenia

in a Newborn

Susan

Sencer,

MD, Alison

Coulter-Knoff,

MD,

Deborah

Day,

MD,

John

Foker,

MD, Theodore

Thompson,

MD, and

Barbara

Burke,

MD

From the University of Minnesota Hospital and Clinic, Departments of Pediatrics, Family Practice, Surgery, and Laboratory Medicine and Pathology, Minneapolis

ABSTRACT. The case report of a newborn infant with a

splenic hemangioendothelioma with the life-threatening

complications of thrombocytopenia, anemia, and

dissem-mated intravascular coagulation is presented together

with a review of the literature. Removal of the tumor via

splenectomy, despite the known risk of subsequent

over-whelming sepsis due to encapsulated organisms in the

young child, is the treatment of choice for splenic

heman-giomas complicated by thrombocytopenia. The use of

enhanced CT with delayed filling is a diagnostic tool in

the workup

of suspected

hemangiomatous

lesions.

Pedi-atrics 1987;79:960-966; spleen, kemangioma, heart failure,

newborn, thrombocytopenia.

Capillary

hemangiomas

are

common,

usually

be-nign,

congenital

tumors

in

humans.”2

Although

platelet

trapping

and

disorders

of the

coagulation

system associated with such tumors

of

large

size

have

been

reported

since

the

original

paper

of

Kas-abach

and

Merritt3

in

1940,

we

report

the

first

proven

case

of a splenic

hemangioma

causing

life-threatening

thrombocytopenia

and

disseminated

intravascular coagulation in a newborn infant.

CASE REPORT

C.N. was the 3,250-g female product of a 38-week

gestation to a 22-year-old, AB positive, gravida 2, para 1,

abortus

1, married white woman whose pregnancy was

uncomplicated.

No medications

were

used

and

no

infec-tions were noted. Labor was complicated by variable

decelerations noted on external fetal monitor and

meco-nium-stained amniotic fluid. Forceps rotation and

ex-traction were performed, and after the vaginal vertex

Received for publication June 9, 1986; accepted Aug 4, 1986.

Reprint requests to (B.A.B.) Mayo Box 609, Harvard at East

River Rd, Minneapolis, MN 55455.

American Academy of Pediatrics.

delivery, the infant was immediately intubated and clear

fluid below the vocal cords was suctioned. Apgar scores

were 7 at one and five minutes.

On

admission

to

the

neonatal

intensive

care

unit

(NICU), the baby’s BP was 50/30 mm Hg, pulse rate 170

beats per minute, and respiratory rate 60 breaths per

minute. She was pale and jaundiced with petechiae over

her scalp and buttocks. She had a large right parietal

cephalhematoma. No hepatosplenomegaly was initially

reported.

Her

initial

hemoglobin

concentration

was

11.2

g/dL,

which declined to 6.5 g/dL by 1 1 hours of age. Her

initial platelet count was 15,000/L with coagulation

study results consistent with disseminated intravascular

coagulation. An exchange transfusion was performed and

a regimen

of antibiotics

begun.

By

day 2 of age, vital

signs remained stable but a grade I/VI systolic ejection

murmur was noted. Blood and CSF cultures were

nega-tive. Splenomegaly, with the spleen tip palpated 2 cm

below the left costal margin, developed. A

contrast-en-hanced

abdominal

CT showed

splenomegaly

with

homog-enous splenic parenchyma. Results of cranial

ultrasonog-raphy were normal.

Her

17-day

hospital

course

was characterized

by

per-sistent anemia, thrombocytopenia, and disseminated

in-travascular coagulation. Her hemoglobin concentration ranged from 6.5 to 11.3 g/dL despite multiple

transfu-sions; her platelet count ranged between 8,000 and

25,0004zL. Cultures for bacteria and viruses were

repeat-edly negative as were TORCH titers. Peripheral blood

morphology

demonstrated that the moderate anemia was normochromic and there were RBC fragments present. Evidence of increased erythrocyte regeneration, marked

thrombocytopenia, reactive lymphocytes, and a

leuko-erythroblastic reaction were also present. Mildly

hyper-cellular bone marrow with a slight increase in

megakary-ocytes

and moderate erythroid hyperplasia was found on

bone marrow biopsy. Increased polychromasia, presence

of spherocytes, and thrombocytopenia were present.

Erythrophagocytosis was minimal.

Moderate-dose

steroid

therapy

was begun

at three

days

of age with no appreciable effect. -y-Immune and

(2)

ex-change transfusion was performed without lasting

im-provement in the hematologic values.

At 18 days of age, she was transferred to the NICU at

the University of Minnesota Hospitals. Vital signs were

normal as were body measurements, and she had

expe-rienced a 280-g weight gain since birth. She was pale and

alert.

Significant findings on physical examination included

a large, right parietal cephalohematoma, a distended

ab-domen with increased venous markings, a liver edge

palpable 3 cm below the right costa! margin, and a spleen

tip palpable 3 cm below the left costal margin. An IV

catheter cutdown site oozed blood, and numerous

pete-chiae were noted on her extremities and trunk. She had

poor head control, increased deep tendon reflexes, and

sustained clonus in the upper and lower extremities.

Repeated evaluations revealed her splenomegaly to be

increasing.

Admission laboratory findings included the following

values: hemoglobin 7.8 g/dL, platelet count 19,0004zL,

prothrombin time 18.4 seconds, partial thromboplastin

time 37.5 seconds, thrombin time 28.7 seconds, fibrinogen

20 mg/dL, and fibrin degradation products 160 zg/mL. A

chest radiograph showed mild cardiomegaly and haziness

of the vascular markings, suggesting interstitial

pulmo-nary edema (Fig 1).

Fig 1. Chest and abdominal roentgenogram

demon-strating mild cardiomegaly, interstitial pulmonary

edema,

and splenomegaly.

Radiology

An abdominal ultrasound demonstrated massive

sple-nomegaly with diffuse increased echogenicity ofthe entire

spleen. No focal lesions were identified within the spleen,

and the liver and kidneys appeared normal. Because of the widened pulse pressure, cardiomegaly, and pulmonary edema, an unenhanced abdominal CT was performed,

and it showed multiple ill-defined, irregular,

predomi-nantly peripheral low-density focal splenic lesions. These

lesions became more apparent for approximately three

minutes after a bolus injection of IV contrast, which was

due to the intense opacification of the surrounding

splenic tissue. As the lesions became more dense, they

appeared to gradually shrink in size because of peripheral enhancement as they became isodense with the

surround-ing splenic tissue (Fig 2). The roentgenographic findings,

in light of the clinical findings, were believed to be

pathognomonic of a splenic hemangioma or an

arterio-venous malformation.

Management

At 20 days of age, the patient underwent a

splenec-tomy. She received cryoglobulin, platelets, fresh frozen

plasma, and RBCs during surgery, which was performed

without complications. The child had almost immediate

correction of her abnormal hematologic and coagulation

values postsplenectomy with an increase in her platelet

count to 132,O00/tL, hemoglobin to 12.9 g/dL, and

fi-brinogen level to 0.26 g/dL. Her coagulation

measure-ments became normal. The following day, fibrin

degra-dation products value was 30 g/mL. At the time of

discharge on postoperative day 4 (without further

trans-fusions),

all laboratory study results were normal. Her

weight, height, findings on neurologic examination,

Fig 2. Dynamic abdominal CT scan. Initial view shows

multiple low-density focal splenic lesions that become

(3)

hemoglobin concentration, and platelet count are normal

at 6 months of age.

Pathology

The resected smooth spleen weighed 110 g (expected

weight 1 1 ± 4 g) and measured 8 X 4 X 3.8 cm. On cut

section, the entire spleen appeared dark red and spongy

(Fig 3). Histologic sections revealed that only one

micro-scopic focus of normal splenic parenchyma could be found

beneath the capsule. This focus fused imperceptibly at

its deeper portion with a vascular tumor that almost

totally replaced the spleen. The lesion consisted of many

small vascular nodules separated by dilated sinusoids

containing developing hematopoietic elements, fibrin,

platelets, erythrocytes,

and

numerous macrophages (Fig

4). Abundant iron pigmentation was demonstrated in

Prussian blue stains. The appearance was uniform

Fig 3. Cut surface of the spleen shows diffuse replacement of normal parenchyma by

spongy

vascular

tissue giving it a finely cystic appearance.

Fig 4. Splenic lesion consists of vascular nodules separated by dilated sinusoids

contain-ing macrophages, erythrocytes, fibrin platelets, and developing hematopoietic elements

(4)

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DISCUSSION

We

have

presented

a case

of a newborn

infant

with

a massive

hemangioendothelioma

almost

com-pletely

replacing

an

otherwise

normal

spleen.

The

patient

had

many

of the

reported

complications

of

such lesions including thrombocytopenia,

dissemi-nated

intravascular

coagulation,

anemia,

and

evi-dence

of high-output

cardiac

failure.

What

is

unu-sual

in

this

patient

is

the

onset

of

hematologic

abnormalities

at such

an early

age.

Hemangiomas

are

the

most

common

benign

tu-mors of the spleen,2’4 but small tumors are rarely clinically significant and, thus, go unreported. A

review

of

the

world’s

literature

revealed

only

14

cases of large splenic hemangiomas in the pediatric

age

group,

with

an

average

age

at presentation

of

4.9 years

(Table

i).’

The

youngest

child

with

a

previously

reported

large

splenic

hemangioma

was

a 4-month-old

infant.6

We

have

included

the

5-week-old

patient

of Dargeon

et a!”

who

similarly

presented

with

a bleeding

diathesis

at

birth.

Al-though

the

spleen

was

reported

to

be

“huge

and

nodular”

to palpation,

neither

biopsy

nor

autopsy

was

performed

which

would

have

proven

splenic

hemangioma

in this

child

with

multiple

angiomas.’1

Our

patient

is only

one

of

five

pediatric

patients

who

presented

with

what

appears

to be

a

heman-gioma

confined

to the

spleen.

The

others

had

mu!-tiple

hemangiomas,

most

often

of the

skin,

other

viscera,

and,

in four

cases,

bone.

Kasabach

and

Merritt3

first

reported

the

combi-nation

of a large

hemangioma

with

thrombocyto-penia

in 1940.

Zervos

et al’3 were

the

first

to report

a solitary

splenic

hemangioma

complicated

by

thrombocytopenia.

The

seven

pediatric

patients

with

Kasabach-Merritt

syndrome

complicating

a

splenic

hemangioma

are

reported

in Table

2. The

thrombocytopenia

is secondary

to local

trapping

of

platelets

within

the

tumor

itself,18”9

possibly

tu-mor.2#{176}

Warrell

et

a!2’

showed

that

platelets

were

actively

consumed

in

the

hemangioma.

However,

within

the

same

individual,

considerable

heteroge-neity

existed

with

respect

to hemangioma

platelet-trapping

ability.2’

This

finding

may

partly

account

for

the

inconsistent

findings

of

the

presence

of

platelet

thrombi

within

the

tumor.22’23

Kontras

et

al’9 demonstrated

both

intratumoral

platelet

trap-ping

and

an in vivo

reduction

of platelet

half-life

in

these patients, this reduction being longer than

would

be

predicted

if platelet

antibodies

were

the

cause of the thrombocytopenia. These authors also

noted

that

platelets

concentrate

coagulation

factors

and

release

them

when

they

clump.’9

Clumped

and

damaged

platelets

then

may

not

remain

in

the

hemangioma

but

be cleared

by the

reticuloendothe-hal

system.

A precise

mechanism

for

the

inverse

relationship

between

size

of

the

tumor

and

the

number

of

circulating

platelets

has

not

been

de-fined,

although

Shim24

reported

thrombocytopenia

in cutaneous

hemangiomas

as small

as 5 to 6 cm.24’25

In 1959,

Gilon

et a!26 and

Beller

and

Ruhrman27

first reported low levels of fibrinogen as we!! as

thrombocytopenia

in

some

patients

with

heman-giomas.

In

all

five

pediatric

patients

with

Kasa-bach-Merritt

syndrome

and

splenic

hemangioma

for

whom

fibrinogen

levels

were

obtained,

signifi-cant hypofibrinogenemia was noted. Wochner et

a!28 demonstrated

direct

evidence

for

accelerated

turnover

of

fibrinogen

during

the

intravascular

clotting associated with Kasabach-Merritt

syn-drome.

Thatcher

et

al’4

pointed

out

that

most

of

the

reported

cases

of hemangioma

and

hypofibrin-ogenemia

occur

in older

children

and

adults,

sug-gesting

that

the

tumors

have

been

present

for some

time prior to the development of

hypofibrinogene-mia.

They

further

postulated

that

inapparent

trauma

to the

hemangioma

itself

may

lead

to

intra-tumoral

coagulation,

especially

because

thrombo-cytopenia often precedes a decrease in fibrinogen

level.14

The

present

patient

had

a low

fibrinogen

level

noted

at eight

hours

of age.

It is possible

that

TABLE 2. Pediatric Patients With Splenic Hemangioma and Kasabach-Merritt

Syn-drome* Case No. Reference No. Platelets (cells/xL) Fibrinogen (mg/dL) Trea tment . Heparin .

Blood Steroids Splenectomy

Products

7 11 68,000 NR U

8 12 50,000-100,000 NR U U

9 13 25,000-60,000 50 U U S

10 14 12,000-33,000 40 U U S

11 15 4,000-36,000 24-76 T U U S

13 17 37,000-84,000 40 T S

14 15,000-20,000 20-74 U U S

(6)

some

splenic

trauma

may

have

occurred

at the

time

of birth.

Some

juvenile

hemangiomas

have

been

success-fully treated with prednisone; however,

corticoste-roids are

of limited

value

in the

treatment

of

asso-ciated thrombocytopenia.’7’24’25’29 As can be seen

from

Table

2, the

thrombocytopenia

of all patients

with

Kasabach-Merritt

syndrome

and

splenic

he-mangioma

was

refractory

to

treatment

with

ste-roids, heparin, and

blood

products. In this case,

splenectomy

resulted

in an

immediate

and

perma-nent cure of the patient’s thrombocytopenia,

dis-seminated

intravascular

coagulation,

and

anemia.

Congestive heart failure secondary to

arteriove-nous

shunting

is another

reported

complication

of

large

hemangiomas.3#{176}

Although

heart

failure

has

been

of

particular

concern

in

patients

with

liver

hemangiomas,31

ours

was

the

only

patient

with

splenic hemangioma who

had

clinical

findings

suggestive of

high-output

congestive

heart

failure.

CT

was

helpful

in

the

diagnosis

of the

splenic

hemangioendothelioma in our patient. It is

essen-tial

to tailor

the

CT

examination,

especially

when

a vascular

lesion

is a diagnostic

consideration.

Be-cause vascular lesions may be of variable density in

relation

to

surrounding

parenchyma,

both

unen-hanced

and

enhanced

CT

scans

are

necessary.

In

the present case, the first CT was interpreted as

normal

because

the

lesions

were

isodense

with

the

surrounding

parenchyma

when

the

scan

was

ob-tamed.

A dynamic

scan

consisting

of multiple

scans

during

several

seconds

at one

level

will

define

the

enhancement

characteristics

of a vascular

lesion.

In

the

present

case,

the

delayed,

peripheral

en-hancement

pattern

and

isodensity

of the

lesion

on

delayed

films

are

radiographic

characteristics

of

vascular

lesions

of the

liver,

including

angiomas,

hemangioendotheliomas, and cavernous heman-giomas.3235 There are no previous reports of the

CT

characteristics

of vascular

splenic

lesions,

but

they

appear

to be similar

to hepatic

vascular

lesions.

Although

numerous

terms

have

been

applied

to

the

splenic

lesions

in these

children,

with

the

ex-ception

of case

2 (Table

1) which

was

a

fibroan-gioma,

they

are

benign

cavernous

or capillary

he-mangiomas or hemangioendotheliomas

histopath-o!ogically.

Although

true

malignant

vascular

tu-mors (angiosarcomas)

of the

spleen

have

been

re-ported

in children,

including

one

infant,

they

are

rare and highly lethal.2’3638

ACKNOWLEDGMENT

The authors thank Drs Rod Kreuger and Michael

Bronson of St Mary’s Hospital, Duluth, MN, for their

help and Debra Lozowy for typing the manuscript.

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37. Smith CE, Rusk GY: Endothelioma of the spleen: A study

oftwo cases, with review of the literature of primary

malig-nancy of the spleen. Arch Surg 1923;7:371-414

38. Brooke A, Hafez GR, Trig M, et al: Angiosarcoma of the

liver and spleen in an infant. Pediatr Pathol 1984;4:331-339

BIRTH OF HALITOSIS

The

heroic

age

of advertising

created

needs

out

of thin

air.

The

need

for

mouthwash,

for

instance.

Gerard

Lambert

had

inherited

a company

that

made

a lotion

used

first

as a surgical

antiseptic

and

then

as a treatment

for

throat

infections.

He

didn’t

really

care

how

it was

used,

so long

as he could

sell

a lot

of

it.

Together

with

two

copywriters,

Lambert

hit

on the

idea

of promoting

Lister-me

as a “mouthwash”

in the

early

1920s.

Having

invented

the

cure,

the

three

men

proceeded

to invent

the

problem,

which

they

called

“halitosis.”

The

country

was

soon

informed

of its existence

and

dangers

in a series

of advertisements.

Submitted

by Student

(8)

1987;79;960

Pediatrics

Barbara Burke

Susan Sencer, Alison Coulter-Knoff, Deborah Day, John Foker, Theodore Thompson and

Splenic Hemangioma With Thrombocytopenia in a Newborn

Services

Updated Information &

http://pediatrics.aappublications.org/content/79/6/960

including high resolution figures, can be found at:

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