From www.bloodjournal.org by on December 3, 2007. For personal use only.

1960 15: 197-211

The Role of Splenectomy in the Management of Thalassemia

CARL H. SMITH, MARION E. ERLANDSON, GERTRUDE STERN and IRVING SCHULMAN

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From www.bloodjournal.org by on December 3, 2007. For personal use only.

B L 00
FEBRUARY, 1960

D
of Splenectomy

Th e Journal

of Hematology
VOL. XV, NO. 2

The

Role

in

the

Management

of Thalassemia
By
CARL

H.

SxIITH,

MARION IRVING

E.

ERLANDSON, ScIlULLAN

GERTRUDE

STERN

ANI)

HE EXTRAORDINARY acterizing the congenital has

PROGRESS hemolytic

made disorders phenomena kept pace from the

in

recent years has clarified

in charmany of

the clinical, hereditary anemia. Treatment urgency for corrective disease in the growth Available determined and that formation strated level of compatible erythropoiesis in

and hematologic not, however,

measures stems

associated with these

increased

with Cooleys advances. The recognition of the and a from

areas of the world beyond those originally designated of populations with susceptil)le individuals. evidence indicates that this disease represents hemolytic it also involves for which there homozygous anemia resulting
in
flO

genetically defect red cell demona of

from

an

intracorpuscular synthesis It has of by of the cell and been

abnormalities is as yet Cooleys

hemoglobin specific therapy.12 that the

anemia destruction is greatly the

problem

establishing erythrocytes inability destruction,

equilibrium between with normal activity to compensate for

and production exaggerated rate

accelerated

of red

and that this inadequacy fusions are therefore which red cell production however, iron cessive, compatible entails with splenectomy deposition. When normal

is greater than in other hemolytic anemias.3 Transrequired to support the adequate hemoglobin levels fails to achieve. The need for continuous transfusions, of the must blood activity be producing functioning of children our clinic review.
particularly over a

problems

blood and considered.

procurement, to Additional discomfort of adjacent with in the

past with
period

reactions maintain from symptoms indications

and hemoglobin

excessive levels exmassive presence Cooleys data are splenectofrom the to 9 years

requirement freedom

becomes are

enlargement of the spleen and interference with the From

anemia

from its mechanical organs. (homozygous) 26 years, sufficient

have data
of

the who

large have

number attended

severe

available mized.
splenectomized

in 58 to warrant This paper is

patients

Half of these concerned

postoperative

patients

been obtained

5 months

tile Department of Pediatrics, 1/ic New )crk Ilos;)ital-Corllell Medical Center. This investigation was supported by grants from tise National Institute of Arthritis and Metabolic Diseases, U.S .P.H .S. (RG A-227 (C9), and The Childrens Blood Foundation, Inc. Read in part before the American Society of Hematology. April 26, 1958, Atlantic Gift,, New Jersey. Submitted Apr. 27, 1959; accepted for publication June 3, 19.59.
From 197

From www.bloodjournal.org by on December 3, 2007. For personal use only.

198
for tions operation.

SMITH,

ERLANDSON,

STERN

AND

SCHULMAN

whom
are

presplenectomy
summarized Many of in

data
other

were
patients

also been

obtained.
as long as

Postsplenectomy 20 years experience whom will

of

observa-

following
report,4

the group has

these

patients

have

the

subject in

of a previous of this splenectomy deal

so that the present at a later period,

been performed

data embrace the and of four additional

since

accumulated patients This

delineation

the effect

earlier topics of
:

report.
further

presentation on the basic

specificalthe need

ly for

with

the

following the in the

the

extracorpuscular disease, developmental to intercurrent

hemolytic
patterns, infection.

defect,
cardiac

splenectomy the

transfusions

postsplenectomy complications and

period, abnormal

growth and response

PATIENT An the function are trast fore, It of required to can is the of usually important The as given close 1) of of the were was blood current urgent routinely observation facilitated were group and evaluation basic disease. for effectively to severely hemoglobin be also made that of the Patients thalassemia without maintain affected effects with fall transfusions, hemoglobin patients, ranging clinically. the in to of by provided had hence 49 the of

MATERIAL splenectomy the into levels those from hemoglobin of our of on previously were not blood clinic, higher the a 58 routine been establishment 7.4 homozygous two and the in to level for will levels.

AND must

MEl-lions take disease into in if multiple with intermediate Gm./100 which levels lower with to ml. blood of over-all homozygous out-patient nine to at the prescribed hospital remaining only hemoglobin account whom the

the both
intermediate supplements

variability parents if of In

of are they blood conconthere-

heterozygous

classifications: severe the 9.9 for minimal lead children of basis. admitted commensurate

normal group This is 6.5

activity. maintained separation, given to 8 be

centrations

taken than

into in!. if

consideration. hemoglobin, is The (table fusions many fusions blood

administration practiced maintain

Gm./100

requirements Cooleys clinic where patients when

anemia transand translevels.

a special The

maintained

RESULTS

PreIn patients

and
our

Postsplenectorny
earlier study

Survival the fate spleen

of Donor of normal employing

Erythrocytes transfused the that

tag for

blood Ashby the life

was span

determined of of has differential transfused facilitated patients of red in and

in

with

an

intact

method

agglutination.4 erythrocytes The the

culation. use of determination

It appeared decreased with

radioactive of

in this advancing
chromium

study age.
as a

erythrocytes

the half limit

life

span subjects

of normal show

donor that after

red

cells the

in the injection

circells 26 in

Studies with The Cr51 upper

in normal

tagged days.56

the isotope of the half days.8 range many

disappears period has

from the been given investigation of chromium

circulation as 32 days7 26 to tagged

one study were taken

as high as 40 as the average observations there are

In the present of the half-life employing exceptions survival children, cells than

32 days cells. 1) be-

More extended demonstrate that tween earlier show

chromium-tagged to the inverse

cells (fig. relationship

age of the patient and the group. Two of the younger a shorter survival of donor

of normal donor cells noted in the A. Y. and V. P. (cases 3 and 4) do the older patients A. C. and

From www.bloodjournal.org by on December 3, 2007. For personal use only.

SPLENECTOMY

AND

THALASSEMIA

MANAGEMENT

199

Table

1 ..-Severe

Cooleys

Anemia
Living Dead

Total Splenecto

no.

of

patients:

58 29

44 16

14 13

mized:

00

90

80

70
I.,

z
60

w
ILl

50

a.

g
0

!?

40

30

20

I0

20 TIME-DAYS

25

30

35

Fig. 1.-Cooleys anemia. Cr51 RBC survival studies (donor cells) on nonsplenectomized patients. Note the shortened survival of normal donor red cells. There is no uniform relationship between the age of the patient and life-span of the red cells,although the longest red cell survival occurred in J. V.. P/2 years old, and the shortest in M. M., 18 years old. F. P. (cases the youngest whereas the in this early could \Vith time
adolescence-in

7 and of the shortest The and

8).

On group, survival other

case

the

other

hand,

in donor in M.

J.

V., 1#{189} years

of age the oldest be

(case 9), normal, patient present until

survival cf occurred hand it is an may acquired

cells approximated M. (case 1), the defect may The

responsible

group. in life

extracorpuscular
any

hemolytic not

therefore
of for its

on the

be manifest defect.
factor

in marked
number

degree
transfusions causation.

thus appear the development of normal

to be

only of the cells,

a possible complication splenectomy, in patients to a lesser

of in

a markedly our experience,

shortened eventually

survival be-

donor

comes mandatory, as occurred Moderate leukopenia and,

1 to 6. extent, thrombocytopenia,

observed

From www.bloodjournal.org by on December 3, 2007. For personal use only.

200

SMITH,

ERLANDSON,

STERN

AND SCHULMAN

00

00

90

90

80

80

70

70

z
z
4 ILl Ui

60

60

50

50

a.
0
U)

40

40 30 20
I0

30

20

I0

20

25 TIME-DAYS

30

35

40

45

50

Fig. 2.-Cr51 RBC tomized patients. in a fair

to

studies

showing

normal

donor

red cell survival in splenec-

number he noted (case

of our in 1)
ranged

cases
to

prior

to

splenectomy,

may

be

attributed except

either for half-

a hyperactive

spleen2#{176} or

suppression

It patient life
are as

will

the with
from

postsplenectomy a red
of lower as perhaps normal

by multiple period (fig. of 25 days The fact

either

transfusion. 2) that the

J.
above range

F. the

cell

survival
suggests

chromium

in the the

others of

34 to 43 days. than more

in other

upper
normal anemia,

limit
is

extensive
refractory

that most of these values that 26 to 32 days given data would warrant, or
anemias, survival of

that in Cooleys donor red cells is the observation (3 months

remained to normal.

is

prolonged that regardless

following of the the

to

splenectomy. length of the span of transfused

survival

Of great postsplenectomy normal

rates in

importance period donor cells group of mechanism effects of

patients in this
splenectomy.

20 years; fig. 2) This reversal confirms the evidence disease and provides

life an

normal

this

for one

extracorpuscular for the

hemolytic beneficial

explanation

PreIn ment globin

in

and these

Postsplenectomy patients

Transfusion as in those previously

Requirements reported4 the progressive develop-

of accelerated transfusion requirements to maintain an adequate hemolevel necessitates consideration of splenectomy. \Vhile efforts are made immediate presplenectomy so as to defer period splenectom, to the vary blood the number and size of transfusion requirement nevertheless

the

the

From www.bloodjournal.org by on December 3, 2007. For personal use only.

SPLENECTOMY

AND

THALASSEMIA

MANAGEMENT

201 for the operation is usually forced.

becomes

so

extreme

that

the

decision

The increasing need for transfusions before splenectomy and the sharp reduction after this procedure is obvious in this group of patients. The striking diminution in the number of transfusions following splenectomy is the fused that and result transfusions hemoglobin of seveial possess synthesis. factors, a one of which In is the addition longer it has endogenous is clearly normally transfusions and hemoglobin of the result. of growth by patient. and survival been of transerythrocytes, as mentioned above. demonstrated in

suppressive This inhibiting

effect on effect which \Vhen capacity

erythropoiesis demonstrated exists are

the decreased stantial amounts following

proceeds

synthesis of fetal hemoglobin in severe Cooleys anemia.9 this

in

in subreduced synthesis Greater

splenectomy
maximally

function with

is

restored the

accordance

amounts of both fetal and adult types It is possible that in later adolescence metabolic removing
sistence on

of hemoglobin cessation factors achieved

diminishing levels. patients of By sub-

needs hemolytic blood

permit and

adequate inhibitory

functioning origin becomes

at lower

hemoglobin splenectomy, in older blood that should in

of endogenous

a possibility In that event therefore,

except when tion will be

eliminating

infection necessary. the life

or trauma supervenes. It is to be expected, hemolytic of normal therefore, After blood donor greater an initial requirements span

supplementathe results be manifested transdecreased

extracorpuscular

mechanism cells, resulting

in an

increased

fusion requirements 3) is cited an an of intermittent necessitate 34 days the

onset operation,

and example.

erythropoiesis. period in the increased

Patient V. first months so markedly

P. (fig. of life as to

transfusions, in

splenectomy. is reflected
of

The increase in half-life of donor blood a lessened need for blood supplements.

from 14 to Comparing the the least conof well

amounts the it

of packed red cells expressed in three month periods from disease until splenectomy with the three years following is apparent that less blood
was required

to gain to

maintain in the weight sense

at

as good and at times improved hemoglobin Another feature worthy of note in this current
being

levels. patient is the related size. monthly

with with

splenectomy removal estimate

which of the

is undoubtedly of inordinate average

of an organ

A quantitative

transfusion

requirements

in terms of milliliters of packed cells was made in 13 children for one year preceding splenectomy and for the subsequent postoperative period (fig. 4). The preoperative period of one year was chosen as a basis for comparison because it was associated with a progressive demand for the administration of blood.
single transfusions

T.
transfusion

P.
in

is still
for

in the first year of observation and study purposes in the first postoperative months the this
first

R.

P. received year and

were

a 10

the

67 in

that

followed. bcre that than

Transfusion year to

requirements determine

especially the need plements. immediately observed, only slightly

compiled

postsplenectomy

whether supneeded will year But in be are each

for blood in It is sometimes following that less the and

period assumed requirements

any relationship lesser amounts in in those the the of following first the later

to subsequent of blood are years. years. It postoperative

splenectomy blood gradually parallel

From www.bloodjournal.org by on December 3, 2007. For personal use only.

202

SIITII,

ERLANDSON,

STERN

AND SCHULMAN

JI?J
(9

1=J::
,-.---

;
.-,?
,

PAr/ENT

C/)

1/2 10

/4 days i 20 i
-

r
-

1/2:34
11

---- - 20

days

i-

bYS-l0
_l

30

0 0

h:
-

1000

_______

SPLENECTOMY

AGE -YEARS

Fig. 3.-Cr5 donor case (V. P.) in which following splenectomy gain in weight is also instance to maintain Effect The splenectomy intracorpuscular the principal is the rium. level The improvement preoperative

RBC survival studies pre- and postsplenectomy of a typical the half-life of donor erythrocytes rose from 14 to 34 days with a lessened need for transfusions. The postsplenectomy apparent.
was

noted hemoglobin

with

respect levels.

to reduced

blood

requirements

of Splenectorny subsequent must

on the course be of

Ba.sic these as

Disease patients
fringe

indicates
benefits,

that
for

the the

results fundamental

of of

regarded

defect yardsticks at which measurement the

of the disease by which the individual of blood

presumably remains severity of Cooleys establishes and

unaltered. One anemia is evaluated equilibproduction

patient destruction

hematopoietic compensatory facilitated his own red cells destruction in turn

of red blood cells and total hemoglobin has been the patients own chromium-labeled red cells in permitting the measurement of the longevity of environment. involve the The a consideration calculations of the of the mean rates cell of both life, which

by reinjecting circulation, thus in their natural and production from the for is derived a study of of the need

chromium half-life of the patients own cells.3 Only a limited number of patients lend themselves to life span of their red cells in their own circulation because
multiple sample of transfusions in most patients patients after

with two

severe
of

the

tagged

cells

blood would

of such necessarily

reinjection

contain

populations

Cooleys their of red

anemia. Any own chromiumcells, their own

From www.bloodjournal.org by on December 3, 2007. For personal use only.

SPLENECTOMY

. flIHiIhf1iri
QI

AND

TIIALASSEMIA

MANAGEMENT

203
YEAR

PRE-SPLENECTOMY-I YEAR POST-SPLENECTOMY FOLLOW-UP-MONTHS

DTOTAL

U)

52OO1flIrftIftjftIftIftIjjftIr.jlIjI.fJ
FG. 60 mos. J.P 71 mos. V.P. 39 mos. AD. 56 mos P.C. 21 mos. J.N. 76 mos. D.B. 14 mos J.B. 8 mos R P. 67 mos

T.P.

S.S

MG.
60 mos

DE
71 mos

5 99 mos. mos

concentrations and average monthly transfusion requiremilliliters of packed red cells in the pre- and postsplenectomy periods. Note that reduced blood supplements were needed to maintain preoperative hemoglobin levels. They were no different in the first postoperative year (dotted column) from later years (open column).
ments in terms of

Fig.

4.-Hemoglobin

and

the

donors. were own

A group available

of 10 patients in whom tagged cells data within

with

homozygous could their be obtained circulation

Cooleys of (fig. the 5).

anemia survival Two

at had

equilibrium of their
been

chromium

splenectomized.

It will from 6.5 From the

be observed to 19.5 days data assembled

that the half-life as compared with in this figure half-life and

of chromium-tagged the normal survival the two splenectomized own cells group.

red cells ranged of 26 to 32 days. patients that falls Therefore, over defect within the A. D. the red

and R. P. reveal a chromium range of the severely affected cell survival intact spleens, unaltered.
upon

of their intermediate

in these two suggesting that the of

and

patients showed that the basic to study patients any

own

no improvement intracorpuscular possible

erythrocytes

patients with was probably of splenectomy

group must

It is obvious the survival

pre-

small
a

effects
larger

be

investigated

postsplenectomy.

The

Factors

of Growth

and

Development and splenectomy eventually growth

abnormalities

and

While both transfusions prompt gain in weight,

are retarded and these

add to the in height

unaltered

patients well being and sexual develop(figs.

ment

remain

6 and weight at

7). at

The time

children
their

with grow

Cooleys normally rate undergoes

anemia

are a marked

of

average of retardation,

height 8 to 10 so that

and years, they

birth. They

until about

the age

which attain a

growth

From www.bloodjournal.org by on December 3, 2007. For personal use only.

204

SMITh,

ERLANDSON,

STERN

AND

SCHULMAN

00
(9

z
4 Ui Ui

a.
0 I0
U)

20

TI ME-DAYS
=S EVERE COOLEYS ANEMIA COOLEYS AGE (yrs) Hemoglobin (gm./lOOml.) ANEMIA Fetal Hemoglobin % CR51

j=lNTERMEDIATE Classification Pt.

TI/2l

(doys)
12.5 11.5 16.0 6.5

SI. Severe NonJ.V. ILK. LM Intermediate NonSplenectomized Severe Splenectomized

.

10/12 16/12 11/12 12/I? 36/I2

-

4.7 5.9 7.2 7,1

65.6 79.4 50.6 78.3

splenectomized

AS.

9.4

59.7

19.5

Fig. 5.-Cr5 RBC survival studies of homozygous Cooleys anemia (patients cells in patients circulation). The severely affected and intermediate (homozygous) patients as well as the two who were spenectomized reveal equal intracorpuscular defects, as indicated by the shortened survival of their own red cells. Note also the large amounts of fetal hemoglobin and the lack of correlation with severity of the

disease.
very
short final

height.
population,

Secondary

sexual

characteristics

develop

later

than series

in the cease with

atrophy is not

normal

if at all. to several years

Normal after

menses the anemia, in the onset.

are

rare

and this

in our

several

months

Whether

interference and gonadal adrenal

maturation is related or to large amounts

clear.13

to chronic of iron seen

liver pitttitary,

dysfunction, thyroid

Cardiac In
one

Complications common with and

subjected failure ranged

idiopathic of unknown
to

hemochromatosis, cause.
splenectomy. from

cardiac

failure

is a frequent all but incepyears severe now but in-

complicationbo.13

had above.

been

Of the 10 patients The ages at the with of many were

tissue five

so affected time of the

patients

tion and

of heart anemia to

12 to 27 years
the lives before antibiotics transfusions
for increased

20 with they lives Whether

W7hile heart

infection in the failure. responsible

terminated years in Long-term

part

children available, their

iron.

Cooleys succumb are

prolong

nevertheless

From www.bloodjournal.org by on December 3, 2007. For personal use only.

SPLENECTOMY

AND

THALASSEMIA

MANAGEMENT

205 or otherwise, irreverspatients. Splenectomy of Cooleys of the basic failure. from four premature flutter, one of our

fluenced by heavy deposition ible congestive heart failure merely anemia.

disease

of iron inevitably measure to alter

not retard

in the myocardium overtakes these for a specific significantly the occurrence

represents It does
process

a remedial not appear

and year. does

complication the pattern of cardiac

The
months beats

duration
to one

of life followed

from The by

the onset of cardiac electrocardiograms runs of paroxysmal premature fibrillation.

symptoms ranged revealed auricular auricular tachycardia, and in

initially episodes

auricular cases,

fibrillation,

ventricular

contractions4

of ventricular

Pen card itLs One of the unusual acute pericarditis had undergone
findings

of

features in eight

in this patients

series with The

to

was the occurrence of severe Cooleys anemia

11 attacks of whom and has

disease

seven variously
complex

splenectom.
corresponded

trocardiographic

designated
as Cooleys

as that
acute

benign,
a benign

clinical signs, symptoms the adult disease which nonspecific or idiopathic. In a

of pericarditis mechanisms represents etiology may

elecbeen
as

anemia

variety

be
solely in and

involved
a our another clinical patients

in

the

etiology

so

designation. have been ended in recurrences.

pericardial

Sporadic unsuccessful.

attempts All of

to establish a viral our cases were truly one

benign,

self-limited of The unknown. patients, which

have

and two basis Because it seems promotes

thus far

complete recovery, although In only two instances was

effusion, and

child had one there x-ray evidence spontaneously. pericardium splenectomized

a major infection. incident Antibiotics

a moderate

this

also of

cleared the

physical

for

the

peculiar occurred removal

susceptibility

susceptibility

is

pericarditis likely that

increased

almost entirely in of the spleen constitutes

to

this

type

of

proven
Infection

valueless,

and

treatment

consists

of symptomatic

relief.

Increasing previously in
of

numbers reported8 Two

of case reports547 have dealing with postsplenectomy additional anemia one cases of overwhelming have been year previously

further documented those susceptibility to infection and fatal infection child 5 years 48 hours with in One within

children.
age

patients

with Cooleys had a splenectomy sepsis. previously and Two children in whom had patients with

encountered. and died of age sepsis have

and

pneuniococcus

years hours. served These

ficiency

The other child succumbed with without Cooleys but nonfatal

hemolytic occurred in acquired

10 years E. coli anemia

anemia

had a splenectomy four within a period of nine also recently been obinfections
hereditary

serious
meningitis

postsplenectomy the one majority former year of and or less, therapy and seven cases

occurred.
spherocytosis. adrenal insuf-

Pneumococcic

acute

hyperpyrexia

in the Since in

latter, the

years, the interval

respectively, between practice period

following splenectomy to place of two

splenectomy. and infection splenectomized

has been two years patients on antibiotic

it has for

been our a minimal

years.

From www.bloodjournal.org by on December 3, 2007. For personal use only.

206

SMITH,

ERLANDSON,

STERN

AND

SCHULMAN
C V C C

(I)

C C

0.

.C :ff

______
0
I

0 1)

z
I

t-

_J H
.
.

..j h

___
.:

Ii
IV
.

.:#{149}

..f

II!
4

0
I 0

\c_-.

d
cots
.

From www.bloodjournal.org by on December 3, 2007. For personal use only.

SPLENECTOMY

AND

THALASSEMIA

MANACEMENT

207

COMMENTS

\Vhile anemia normal

there
eliminates donor

is

abundant
a hemolytic

evidence
component

that

splenectomy

in

severe

Cooleys of red the be in of cell

cells
patients

probably
own

cells,419 remains
cells may

the gross unaltered.

have been

which shortens the survival destruction of the patients defective The intensity of the destruction of
minimally reduced
,

in

the the

two statement same

splenectom-

ized
made pre-

patients
until and

( A.
more

D.

and

R.

P.,

fig.
are

but

no
out

absolute
in

can patients

extended

studies periods.

carried

postsplenectomy

The collective splenectomy is to destruction hemolytic difficulty

data of re-establish

the the

present study preoperative

indicate that the effect status with regard to red a

and production component. Still in establishing to compensate is greater

and patients. in accounts

now no prevailing for the Cooleys

for

longer influenced by in the splenectomized levels because accelerated anemia the need
is

superimposed patient is the of the inability

adequate
in

hemoglobin

of erythropoiesis This shortcoming

hemolytic majority of anemia these

rate of red cell destruction. than in any other congenital of transfusion therapy in the
proper selection of patients increased, condition.

A critical
for splenectomy. is clearly

problem

Cooleys

anemia

the

In

the
when

severely
transfusion and to differentiate concurrent

affected by

individual
requirements

the
are

need
persistently

for
clinical

splenectomy

indicated at times

by massive It is difficult
puscular red and

splenomegaly, defect

deterioration
between

the

of the acquisition

of an
of

extracor-

hemolytic

cells are insight

or an useful. into
with for

exaggerated
related to

hypoplastic
a minor

with a shortened survival period due to a failure

In such cases, auxiliary

the donor of production

laboratory

frequently

infection.

tests an
patient criteria

Measurements the rate a markedly

with

the

use

of radioactive blood increased that

these

chromium

provides the
un-

at which transfused and persistently

are so obvious

is being destroyed. In transfusion requirement,

measurements are

splenectomy

necessary.2#{176} Additional

benefits

from

splenectomy

accruing

to the

splenectomized thin red Whether in of thickness anemic

low hemoglobin

patient

may stem from the greater oxygen to the tissues than of patients by with
anemia

ability of their cells of greater anemia awaits already study. The

in

naturally thickness.2 reduced ability

spite of

cells to deliver the red cells are patients further with

levels

Cooleys
to

thinned
C3oleys

splenectomy

may perhaps The greater the substantially in this genetically puberty.

needs in

be physically active be explained on this basis. effectiveness of splenectomy reduced postoperative The disease the well function slowing being to and delay of of age permitting

in the transfusion may be and postponement

older

child is reflected in requirements inherent on of the basis of until metabolic

at levels

age

period. milder Also, with with

adolescence

explained

splenectomy

growth
equilibrium

erythropoietic

can

diminished basal be established by adolescence,

compatible Despite the

without splenectomy

supplementation until

transfusions. it is fre-

preference

From www.bloodjournal.org by on December 3, 2007. For personal use only.

208 qtlently already

The

SMITh,

ERLANDSON,

STERN

AND

SCHULMAN

necessary stated. data spleen

in

to remove in of Cooleys the this

the

spleen and other Reports

in the papers of

younger throw and the

in

patient no cytopoietic light

for

the on

reasons the posof to that

compiled in

sible the
infection

modification
children

normal anemia.

immunologic
splenectomy

functions

following

increased susceptibility this disease indicate against invading now in progress phagocytic the spleen. numbers children small.

the immunologic defenses residing in this organ are unimpaired. In the course cf an investigation with the causation of postsplenectomy infections, been found normal regardless of the presence of l)e emphasized ies in Cooleys severe supervision treatment Transfusions and that in comparison with the increasing anemia and in other dyscrasias in overwhelming for several years may be immediately which are an for the infections is relatively in the support postoperatively instituted required increased normal to

organisms concerned activity has again of

It should

of splenectomthe incidence

Nevertheless,

close

is essential so that appropriate event of an infection. adequate hemoglobin accumulates 1 mg. levels
in

pro(luce simultaneously the tissues and, except cannot deposits sites ticularly

iron deposition. Iron excretion of approximately

daily,

leave the body except by bleeding. in normal storage depots increase assume the noticeable in function in of patients iron storage. receiving by the iron to
in

Under such conditions, hemosiderin greatly, and in addition accessory Another minimal gastrointestinal is stored in fibrotic liver areas and source of tissue is tract and cardiac This to the hypoxia, factors
does usually spleen

iron, the from muscle

pariniron as

transfusions, the

creased absorption medicaments. As ferritin. chromatosis change presence

concomitants in tard

from the diet other organs, of siderotic most commonly

The

conversion occurs

characterizing pancreas.

hemoanatomic continued common involved

not occurring re-

the factors Chronic

probably depends cf excessive iron

of Cooleys

on other in tissues.
anemia,22 may to

in addition anemia and

some of the

represent

the
the

production
inevitable

of

hemochromatosis.
irreversible

Removal
heart

of

the
disease

progression

in the The
with

young failure
Ccoleys

Inales trast,
female

with idicpathic
has

adult. to mature normally and menstruate deprives the female patient anemia of the opportunity to unload iron; thus both females and this disorder become susceptible to hemochromatosis. In conhemochromatosis
already achieved sexual

occurs
maturity

predominantly
at an age

in
when

males the of
has

since

the

toms stantial
cessfully

of this

disease of of

are iron by iron

likely through stores

repeated

to in

appear pregnancy,
idiopathic

and

is thus lactation
hemochromatosis In

capable and
Cooleys

first symplosing subbeen anemia suc-

amounts
achieved

menstruation.1 the of the

in

Mobilization need this

urinary

phlebotomies.1323

for measure.

maintaining The
of excretion iron

adequate intravenous
but is

hemoglobin injection
impractical

levels of chelating
in

precludes agents
of

the increases
conditions

use

treatment

which

massive

iron

overload

exists.2425 confronting of heart

Until

specific

treatment

becomes Cooleys when

availanemia other ef-

able, the most serious prcblem is the prevention and control

the failure.

patient with In an era

From www.bloodjournal.org by on December 3, 2007. For personal use only.

SPLENECTOMY

AND

THALASSEMIA

MANAGEMENT

209 the most important iron. need at present

fective is the

therapeutic discovery

measures of a means

are to rid

at hand the heart

of excessive

SUMMARY

A group ectomized, hematologic

Splenectomy

of were

58 aspects.

children reviewed
eliminates

with from the

severe several

Cooleys of the

anemia, more

half important

of

them clinical

splenand for circula-

extracorpuscular donor and red

mechanism cells in the and accounts a striking to

Estimates the

responsible patients for an reduction at

duration hemolytic

the

accelerated

destruction

of normal

tion. This longevity

fusion and of not growth characteristics the at

represents of normal
improved, own significantly

a lasting improvement blood supplements

Less

increased of transas
of defect

requirements. times patients

blood
hemoglobin

was

required
levels.

maintain
of basic

least

good,
is

survival

erythrocytes

suggest

that promote are

in

altered

by and and sexual if at

this

operative

procedure.

While
in

transfusions height rare. failure This and

of life. complications develop,

splenectomy development all, in was

later than

the retarded.
normal

patients
individuals

well
and

being, sexual
normal

Secondary

menses Cardiac splenectomy. arrhythmias

decade Cardiac

are

occurred group death with

are

10 patients; characterized refractory likely are to

be

all by heart related

but

one

had usually the

been in

subjected multiple the second

to

cardiac failure, to in of the

enlargement,

heavy respect

deposition to and of an
in

of
similal

iron in the

in

the in

myocardium, idiopathic of failure.

and Cooleys This

can

comparable One is the on to unload

following

this prevention

incidence congestive
method

hemochromatosis. anemia will

to remain

most

serious

problems control effective

patients

management heart

of

depend
infection

the

discovery its iron

splenectomy

by which the heart The increased susceptibility with severe Cooleys anemia
inherent in

be made that

deposits. responses a continuous

indicates
intact

the
despite

normal the

immunologic stress of

hemolytic

the process.

spleen

SUMMARIO

IN

INTERLINGUA

Esseva clinic

passate

in

revista, le casos

ab
de

plures

del

plus

importante

punctos

de sever

vista de

e hematologic,

58 patientes

pediatric

con

grados

anemia de Cooley. Un medietate (lel patientes haheva Splenectomia elimina le mechanismo extracorpuscular pro le accelerate destruction de normal erythrocytos circulation le prolongate reduction pro tiones
basic intervention

essite splenectomisate. que es responsabile transfusionate in e explica frappante requirite Estima-

le

del del

patiente. longevitate requirimentos le mesme

Isto de

representa normal

un permanente melioration supplementos sanguinee e un

transfusional. e a vices del

non es

Minus
nivellos del patiente
significativemente

sanguine de mesme

esseva

mantener del
defecto

meliorate
alterate

hemoglobina.

superviventia
hemolytic chirurgic.

erythrocytos

suggere que per le mentionate

Ic

From www.bloodjournal.org by on December 3, 2007. For personal use only.

210 Durante su crescentia ticas secundari normal. ception,

acterisate fallimento

SMITH,

ERLANDSON,

STERN

AND

SCHULMAN

que

transfusiones

e splenectomia

promove sexual si del toto, es rar. patientes.

Ic ben-esser es retardate. plus tarde Omne Iste

multiple,

del Le

patiente,

in altor e su disveloppamento del sexo se disveloppa, de menses occurreva subjicite

cardiac, corde, es

que istes,
e

characterisin individuos con esseva

con un

Le occurrentia cardiac essite

allargamento per

normal a

Disfallimento habeva
refractori complicationes

in 10 del
arrhythmias

exdisdel

spenectomia.
durante

gruppo

char-

morte

del
cardiac

usualmente probabilemente

le secunde

decennio

vita.
Le relationate

a! massive

deposiinplus de de
sti

tion de ferro in le myocardio e es simile in iste respecto a un comparabile cidentia de complicationes cardiac in hemochromatosis idiopathic. Un del serie problemas in le tractamento de anemia de Cooley es Ic prevention congestive
un efficace

disfallimento
methodo per

cardiac.
que

Su le corde de de inherente

resolution pote contraher sever

va esser

depender inducite

del

discoperta

a discargar in patientes Cooley indica intacte

de-

positos de ferro. Le augmentate a splenectomia normal del stress responsas de un

susceptibilitate in le tractamento immunologic continue processo

infectiones anemia de remane

subjicite que Ic

in Ic splen

in despecto

hemolytic.
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THALASSEMIA

MANAGEMENT

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