From www.bloodjournal.org by guest on July 28, 2017. For personal use only.
Hemolytic
Disease
A Case
Report
of the
with
a Review
in the
By
PHILIP
Newborn
LouiS
ELIZABETH
T
HE
S FACTOR
the
aid
was
of a serum
by
anti-D
and
along
with
about
56 per
cent
of all
bloods
cases,
the
sidered
as contributing
the
S factor
his
co-workers3
aid
of an antibody
there
are
follows:
to the
is genetically
three
genotypes,
12.28,
Ss 46.4
As
to
destruction.
factor,
with
hemolytic
the
incidence
ss 41.4
s, as
the
of which
In
in
no
the
observations
theoretically
the
thirteenth
The
in
factor
newborns
the
stimulus,
From
St.
the
*
In
sensitized
June
case
VIII,
in
pregnancy)
hydrops
utero
was
due
Rh
an
anid
the
with
Ss system,
populations
group,
nsegative
described
case
the
recipient
of Rh
are
as
value
of
surifered
nsegative
as an isoimmunse
hemolytic
a
blood
antibody
disease
inducing
below,
was
w’hich
represents
the
Foundation,
found
the
free from
ins
with
there
arsy
in
both
This
was
Rh negative
hemolytic
a history
source
the
antibody
is in part
supported
N.
the
J.,
and
of
orse
or
with
due
to
of anstigenic
by
Pathology
given
insdidisease
two infants
reported)
obvious
cases
are
antibody.
was
appar-
the
obser-
Laboratory,
Y.
for
anti-S
Rh
aniti-D
of
VIII *) delivered
(Case
XIII
here
Raritan,
N.
accepted
infant’s
clinically
and
arsti-S
of the
or pregnancies,
variety.
Poughkeepsie,
1952;
presence
without
twice,
contained
characteristics
In 7 patients,
agglutinsins
occurring
Mollison’#{176}
serum
serologic
patients
(Case
and the other
observed
Research
26,
whose
on the
to aisti-D.
atypical
Hospital,
Submitted
the
observed
ins the
by transfusions
was
orsly
Ortho
Levine
5,
of the
white
administration
all 13 patients
of
rsaturally
the
Francis
of
has thus far been observed.
thus far been described,
but
that anti-S
may occur
by itself be capable
of
One of these
due to anti-D
anti-S
of
the
emphasis
attributable
As the
ansti-S.
case,
irs
either
more transfusions.
hemolytic
disease
enstly
showns
special
In 5 cases,
ansti-S
viduals
immunsized
in 3 inistansces
allele
Negro
con-
that
of anti-S.
features
1 with
another
following
irsdicate
it should
as
essential
riot
showed
ansd irs 1951
the
of the
was
S.
example
table
in
reaction
These
so that
of
and
reactions,
transfusion
containing
Sanger2
reacted
anti-S
observed
as an immune
isoagglutinsins
responsible
for
Ins at least orse case, anti-S
w’as the cause
of a fatal
hemolytic
was
disease.
severe
and
In terms
in
cent.
which
majority
anti-S
with
infant,
great
genetic
disease.
per
ins 1947
and
N system,
M arid
Guth
and
Race
.
transfusions
AND
aisti-S,
the
ins
anti-D
is only 2.8 per censt Orsly one example
of ansti-S
In all, 12 examples
of sera containing
anti-S
have
instance
M.D.
Montgomery’
antibody,
ss
hemolytic
Cited
of ann erythroblastotic
arsother
to the
associated
ansd
mother
examirsed.
blood
the
Sera
M.S.
attributed
related
described
6545
it
was
Anti-S
FERRARO,
Walsh
negative
with
disease
R.
KOCH,
discovered
of an Rh
containing
hemolytic
of 12 Anti-S
to
Literature
M.D.,
LEVINE,
Due
publication
(along
negative
July
with
but
symptoms,
to anti-D.
1030
22,
S positive
hut
1952.
anti-D)
the
earlier
in
red
a mother’s
serum
cells.
infant
pregnsanscies
This
ended
which
(sixth
in
fetal
From www.bloodjournal.org by guest on July 28, 2017. For personal use only.
LEVINE,
FERRARO
AND
1031
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From www.bloodjournal.org by guest on July 28, 2017. For personal use only.
1032
HEMOLYTIC
that ins both
temperature.
vations
room
The
varyirsg
that
gests
much
body,
an
like
isoaggluntinin
of
higher
titer
here
with
view
12 cases
instances
is supported
ins which
activity
reactions
the
by the
antibody
involved
The
(Mrs.
mother
M. H.)
at four
TABLE
had
months
two
normal
with
of
of
the
and
in
the
DC
J. H.
M.
OMN
H.
to cause
disease
the
third
Child
1 (1939)
Child
Serum
of
Reactions
With
treated
terminated
by
Mrs.
.1!.
a trarssfusion
H.
-
Serum
Mrs.
Anti-
2 (1946)
Affected
W.
with
so
M.
donor
that
to
8, 1952,
jaundice
within
there
It
Mrs.
The
a transfusion
projectile
cyanotic
and
The
mother’s
M.
F.
(Case
60
+
+
0H
+
+
0++++
+
+
VII
100
and
after
serologic
are
+
+
+
Ss
0ss
Oss
++
+
Ss
virtue
indebted
II
ins table
1).
hours
was
to
in
The
the
parallel
Race
and
and
to
On
developed
15 Gm./100
was
cc.
moderately
to
11 Gm.
2,
typical
for
hensiolytic
kernicterus.
irsdicate
an
demonstration
incompatibil-
of
of a stansdard
Sansger
Drs.
who
dropped
were
and
table
reactions
chill
was given.
The infant
was listmouth,
and became
extremely
findings
by
a severe
was
test
hemoglobin
Ss
administered.
infant
Coombs
splenomegaly
in
was
blood
direct
autopsy
presented
1)
peripheral
when
confirmed
Drs.
table
the
+
with
volume
positive
blood
the nose and
Rh
associated
a full-term
The
hepatomegaly,
of the
(Case
section
of
from
birth.
this
was
small
cesarean
40
0,
findings,
and
0
transfusion
leukocytes.
at
Ss
+++
hemoglobin
per
hours
S factor
Pickles
the
by
The
anemia,
by
+
a comparatively
delivered
increased
jaundice,
authors
by
+
of 100 cc. group
vomiting,
bleeding
died
serum
The
*
studied
H.
hours.
jaundice
complete
of the
ity
M.
after
28 normoblasts
positive.
i.e.,
0
000,+
0+0+
that
terminated
a few
were
MN
is significant
be
per cent,
less, had
disease,
0
0
M.
had
January
and
0
+
+
transfusionl
(1950)
W.
it
and
(1952)
child
Donor
MN
0
(1950)
type
I
M.H.i
0
0 MN
Miscarriage
a
reported
pregnsanscy
was
E
OMN
ars
have
as anti-S.
which
-
Mr.
first
newborn.
________________________________-_
Mrs.
antigenic
l)ecome
CASE
bleeding
.-tnti-S
sug-
to
hemolytic
a
at
anti-
of the
identified
childrers
excessive
Presence
2.-The
A
than
literature
capacity
disease
been
OF
C.
occurring
unnider
properties
potential
a case
has
37
arid on further
stimulations
instance,
the antibody
will
hemolytic
in
at
ins the
which
its
37 C. arid
findings
REPORT
in a miscarriage
variety
latter
as
weakly
as a niaturally
alters
at
as well
ANTI-S
reported
or ansti-Le,
pregnancies,
optimum
transfusion
This
the
ansti-P,
anti-A2,
TO
more
irs rare
in
and/or
DUE
somew’hat
the “irstermediate”
isoagglutinsins.’4
Ins the
“warm”
hemolytic
anti-S
of
NEWBORN
reacted
is present
anti-A1,
transfusions
OF
anti-S
antibody
of
immune
a
sera,
behavior
this
stimulus
DISEASE
anti-S
in
the
ansti’.S.*
for
a supply
of
Rosenfield
ansd
Vogel
the
for
anti-S
their
serum
serum
From www.bloodjournal.org by guest on July 28, 2017. For personal use only.
LEVINE,
The
mating
was
be demonstrated.
positive.
On
weaker
incompatible
The
blood
which
for E, the
disease
for
constairsed
failed
TABLE
obtained
stimulus
husbarsd
was
child
w-ere
the
result
factors
S and
E.
I
6
+
Serum
1
0
+++
+++
0
tests
were
Readings
+++
carried
were
made
out
with
after
4.-Titration
of
I
saline
0
Serum
.11. H.
+
W.F.
for
+
0
I
readings
presence
16,
*
A double
Vogel.9
(lose
0
+±
0
one
Anti-E,
and
minute
Anti-S;
1000
the
4
8
0
0
0101
55
0
0
001
55
+++
+++
+++
++
I
effect
could
obtained.
since
be
0
I
0
+
Ss
I
SS
0
3.
arsti-S
the
ansti-E
arid
elicited
arid
A slight
higher
relationships
riot
I
a very
w’eak
anti-E
is insdi-
0 bloods
show-ni
ins table
3. Of the 26 bloods
each of the 5 bloods
containing
the factor
E
w-ith serum
M. H.
serum
M. H. for
be elicited
SS. * These
0
+
++
ins table
strong
w’ere
Genotype
32
01
0
respectively,
at
Effect
0.
0
47 group
anti-S,
Dose
16
0
015
hour
1:
+
standard
one
----________________
+
as givers
for
r.p.m.
Double
+±
made
SS
incubated
at
+±
the
of
++
+++
reactionss
titration
Ss
+++
a comparatively
fect of anti-S
could
bloods
of genotype
and
.1!. H.
++
++
+++
in the reactions
to react
with
1:8-1:
Serum
ss
+++
were
of
+++
0
+
B.G.
and
the
Anti-S
2
+
0
J.H.
+++
Dilution
1
1).L.
BK.
weak
S negative
anti-s
0
_________________________
Testwnth
____
On
in
I
cells
for
-
gave
hemolytic
of the
0
suspended
censtrifugation
with
cated
failing
compatible
the
anti-S.
±±
±±
+++
+
S
The
serum
Anti-S
Antn-S
±
0
and
The
was
that
E factor.
the donor’s
s With
MH
0
Tests
from
mating
occurring
a Strong
rsot
Genotype
16
___
the
only.
could
the
constainsinsg
it is obvious
and
ansti-c
was derived
Since
of ansti-S
Anli-E
but
negative
and Fy (Duffy)
of selected
bloods,
much
bloods
of a naturally
Reaction
.
+
Cerns of Group
(hr’),
anti-E
(dee/dee),
actions
of a Weak
Presence
5
21
TABLE
c factor
the
of
presersce
Anti-E
These
1033
KOCH
S negative
negative
of the
No.ofGroupO
Broods
Tested
37 C.
w-ith
Rh
the
reveal
3.-The
the
for
productions
both
being
the
to
also
AND
red cells of the parents
w-ere Kell
the mother’s
serum
with
a panel
testing
reactions
Apparently
FERRARO
are
with
titer
ansti-S,
but
w’as observed
presersted
anti-S
values
definite
sera
ins table
of
Pickles4
of
double
1:1-1:2
dose
ins tests
efwith
4.
and
Rosenfield
From www.bloodjournal.org by guest on July 28, 2017. For personal use only.
1034
HEMOLYTIC
r Reference
who
DISEASE
to Cases
I and III
exposed
to antigersic
were
OF
NEWBORN
ins table
stimuli,
DUE
1 reveals
that
gave somewhat
C. thars at 18 C. in contrast
to anti-S
in patiensts
tact as ins Cases
VII and IX. Simultaneous
tests
C. and
18 C. with
prewarmed
TABLE
and
5.-Anti-S
in
precooled
Serum
W.
Temperature
as
a “Warm”
1
2
+++
+++
+++
+++
37
+++
+++
18
+++
++
37
+++
+++
18
+++
+++
18
55
These
tests
serum
respective
for
were
and
carried
saline
hours
out
with
suspensions
temperature
two
and
without
group
8
++
++
++
I
tested.
+
0
0
+
0
0
0
0
0
0
++
+
0
±+
±
I
suspended
and
were
cells
and
precooled
made
32
+
+
+++
Readings
16
+
prewarmed
6.-Titration
of
Anti-S
I
for
after
in
Serum
the
.1!.
II
Saline
1
0
0
0
saline
as a diluent.
10 minutes
tests
at
were
Indirect
H.
III
Coombs
IV
I
Serum-Albumin
Genotype
Trypsinized
Dilution
Cells
1:
8
128
64
64
Ss
8
128
64
64
SS
16
128
128
64-128
SS
16
128
128
64
I
I-saline
suspended
Il-the
second
their
incubated
Red
Ss
saline
centrifugation.
0
of Group
arid
Agglutinin
4
0 saline
were
then
TABLE
Cells
H.
1:
-fif-++
SS
The
M.
1
37
Ss
(serum
Dilution
.
Ss
anti-S
in these
2 patients
stronger
reactions
at 37
reagents
H.
ANTI-S
with iso previous
antigenic
eonof anti-S
in serum
M. H. at 37
I
Genotype
TO
cells
phase
of
arid
saline
diluent.
indirect
the
Coomhs
test
was
carried
out
on Series
I at
room
temperature.
Ill-serum
suspended
IV-the
red
cells
cells
were
and
treated
30
per
cent
for
20
minutes
bovine
albumin
with
a
diluent.
1:100
dilution
of
trypsin
(Difco
1:250).
The
readings
casional
suspended
immune
This
in I, III,
and
IV
were
made
after
inscubation
for
two
hours
at 37 C. with
oc-
shaking.
effect
cells)
show-ed
antibody,
since
the higher
is more
readily
whnch
in table
5.
Greater
activity
differentiate
immune
that
it behaves
titer
demonstrated
at 37 C. than
from
like
naturally
at
a “w-arm”
arid
on 3 of the 4 bloods
with
18 C. is one
occurring
therefore
was
homozygous
of several
anti-bodies.
presumably
obtained
bloods
characteristics
Other
criteria
at 37 C.
is shown
w’hich
w’hich
From www.bloodjournal.org by guest on July 28, 2017. For personal use only.
LEVINE,
are
significant
are
activity
ins proteins
Coombs
test. Accordingly,
arid ins serum-albumin
anti-S
mixture.
cells
same
were
recorded,
particularly
in
susceptibility
higher
of the
also
was
the
the
studied
in the
arid
direct
serum-albumin
higher
face
of the
tionis.
with
this
show
as long
result
preherisive
studies
could
be attributed
H.
cells
w’eak
a
bloods
riot
that
give
SS.
agree
are indicated
to differences
the
Titration
distinct
double
Apparently,
with
to determine
in technical
Coombs,
effect,
a
suir-
experiments,
reactions
in the
titra-
more
com-
Pickles,’5
or riot
anid
i.e.,
on the
Ins other
by
thani
saline
S antigen
the
w’hether
procedunres.
serum-
values
dose
the
reported
conditions
in both
to trypsirs.
that
previously
higher
cells.
to affect
cells
indirect
The
of t.rypsins
several
considerably
failed
action
test
these
technic,
reactions.
to the
with
indirect
Coombs
direct
cells
the
in saline
medium
saline
suspenided
indirect
under
but
hours
with
show’
red
by exposure
as three
does
to
ins saline
suspended
is riot destroyed
for
Since
saline
homozygous
red cells
trypsinization
to the
of the
M.
red
reactions
failed
surface
trypsinsized
tests
with
subjected
resunlts of the titrations
6.
above,
it is evident
mixtirres
value
and
M. H. was titrated
readinsgs
with
the
which
of serum
1035
KOCH
media
were
on the
by titration
mixtures,
those
tests
S factor
AND
ins serum
After
the
dilutions
exposed
to t.rypsin.
The
are summarized
ins table
From
the data presented
albumin
FERRARO
this
discrepancy
DISCuSsIoN
but
A review
of the 13 cases in which
2 instances
there w’as ans anstigensic
S either
irs the
transfused
blood
or
occur
as a naturally
occurring
18 C. than at 37 C. The standard
i.e.,
incubation
curring
at 37 C. are
antibodies
By
one
of anti-S
not
a normal
has
beers
may
anti-S
was
out
at
least
The
most
by
hemolytic
Unfortunately
and
37
react
disease.
the
C. is lacking
regarding
titers
in the
for
that ins all
presensce
of
ansti-S
may
more
strongly
isoimmunizations,
selection
indirect
data
in
Coombs
some
question
the
at
of naturally
arstibodies
weak
oc-
remaininsg
arises
with
this
group
examples
altered
on
anti-S
media.
test
susceptible
for inducinsg
in table
13 cases
Reference
is lacking
arid
1 oh
there
to
ins five
in-
stronger
immune
of anti-
of antitheir prop-
stimulations.
With
onse or more
exposurres
antibodies
may
develop
strong
titer,
more
to sensitize
potential
It
a group
be conivensienitly
intermediate
and probably
some
varieties,
but have
or
stimulations.
isoanitibodies,
may
11
w-hether
reactions
at 37 C., but
other
anstibodies
of the
is that.
anti-N
occurring
of the
to antigenic
of hunmans
immurse
may give
associated
10 of the
ins protein
classify
to exposure
explanation
activity
at 37 C. arid capacity
of Coombs
with
concomitant
and
LTndoubtedly,
but
classifications
and
ansti-S,
ansti-M,
of the naturally
virtue
of anitigenic
blood
factors,
the
variety,
prior
natural
plausible
bodies
(anst.i-Lun,
Lea) are insitially
erties
specific
cells.
suitable
tentatively
ins the
Those
aggluntinins
which
at 18 C., are frequently
variety.
not
immunse
presenst
that
between
cluded.
reactions
red
saline
agglutinin
which
reacts
conditions
of tests
to detect
obviously
as of the
pointed
intermediate
ins fetal
reveals
to the
irs general.
exclusion,
examples
anti-S
has been observed
stimulus
dune presumably
to the
distinct
cells to the anstiglobulin
test
both
transfusions
reactions
comparative
titers
is practically
no insformation
the
cases.
capacity
It must
of
the
at
18
antibody
be borne
in mind,
C.
to
From www.bloodjournal.org by guest on July 28, 2017. For personal use only.
1036
HEMOLYTIC
how’ever,
that
in the
the
w’hile
7 patients
sufficient
who
4 mothers
DISEASE
OF
NEWBORN
quantities
received
more
of serurm
than
of erythroblastotic
DUE
one
be a fatal
form
severe
disease.
previously
when
reactions.
antibody,
it to
If the
then
the
The
only
immune
incidence
factor
antibody
or
saved
the
This
not
hemolytic
pregnancy
anti-S
of an
likely
that
the
of a small
that
with
anti-S
apply
ans S positive
anstibody
volume
w’as
may have
beers inscidenstal
antibody
such as anti-Mis
was
husband’s
was
excluded
blood.
nsot made
a replacement
is unsique
disease.
than
by the
to
was”im-
resulted
presenst
as
in a
a natural
fetus
sufficed
arid
w’ith
that
the hemolytic
an exceedingly
low
absence
Unsfortunately,
until
the
transfusions
at
are
associated
least
since
of the
the
infant
with
it represents
the
It is remarkable
95 per
for
to convert
died
(Miltens-
Mi
identifications
arid
S negative
the
of the
question
(ss) could
blood
cent
14 blood
mothers.
of all insfants
factors
with
that
(K,
hemolytic
This
instance
with
by
does
isot
the
include
itself
arises
have
f,
very
disease
in the
infant.
expect
that
eventually
also be shown
to cause
antibodies
born.
Judging
from
antibodies
hemolytic
disease,
Jk,
by themselves
are
case
inscapable
Rh
3 factors
with
anti-D
or
for the hemopaper,
mentioned
one may
will
above
naturally
hemolytic
s, Mja*)
5,
for
in this
that
for
of mainly
antibodies
presented
of inducing
k,
group
for the 3 blood
factors
disease.
It is nsow clear
caused
antibodies
Fy’,
small
isoimmune
the
anti-S
is responsible
hemolytic
e, E, A, B, C, Cw,
in
ins which
anti-D
affected
disease
list
first
while
(e, Fy,
Tj)
w’hieh
although
present
by themselves
or along
other
antibodies
have
thus far riot beers reported
to be responsible
lytic
available
not
infant.
case
positive
It is very
is made
reactions,16
ins the
as arsti-S
whether
more
that
result
of positive
berger)
been
does
variety.
possibility
was
the
disease
have
this
the evidence
presensted
in tables
2,
is of the “warm”
immune
variety.
of an insfanit with
what
proved
to
transfusions
assumptions
one
riot
infants.
of hemolytic
tw’o years
may
ANTI-S
transfusions,
With
regard
to anti-S
in the present
case,
5, arid 6 leaves
no doubt
but that the antibody
This is supported
also by the clirsical
history
munse”
TO
disease
occurring
of the
new-
The
sero-
SUMMARY
The
logic
ins
first
case
of hemolytic
properties
12 other
disease
attributable
of this
example
of anti-S
sera
reported
in the
anti-S
is
to anti-S
fully
literature
is reported.
described.
The
are
summarized.
briefly
essential
findings
ADDENDUM
Shortly
for
after
hemolytic
blood
this
paper
disease,
was
was
is-as
submitted
by
prepared
found
E.
the
the
in
C. Zaino,
second
serum
Mercy
example
of another
Hospital,
of anti-S
(Mrs.
Rockville
responsible
L. B. J.)
Cerster,
whose
N.
Y.
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*
importance
C.
MONTGOMERY,
AND
Nature,
possible
inn hemolytic
London
exception
disease.
M.:
160:
of
A new
A and
human
isoagglutinin
subdividing
the
MN
1947.
504,
B,
these
factors
are
arranged
in order
of their
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From www.bloodjournal.org by guest on July 28, 2017. For personal use only.
1952 7: 1030-1037
Hemolytic Disease of the Newborn Due to Anti-S: A Case Report with a
Review of 12 Anti-S Sera Cited in the Literature
PHILIP LEVINE, LOUIS R. FERRARO and ELIZABETH KOCH
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