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1953 8: 620-639

Hemolytic Disease of the Newborn Due to Anti-A

HAL CRAWFORD, MARIE CUTBUSH and P. L. MOLLISON

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Hemolytic
By
HAL

Disease
CRAWFORD,

of the
B.SC.,
M0LLI50N,

Newborn
MARIE CUTBUSH,

Due

to
B.Sc.,

Anti-A
AND

P.

L.

M.D., disease the

destruction

M.R.C.P. newborn serum infant infant-, is made and the

.

T
cells,
is

HE
strating

DIAGNOSIS of hemolytic incompatibility between

w-ith signs of red direct cell

of the mothers find

by demoninfants red
the disease

associated

in the

When

due

to anti-Rh
including

it- is not
a positive

uncommoui
antiglobulin

to

evidence
test in the

of serologic without

incompatievidence found in the of the new-

bility, absence
born

of a hemolytic

process,

of a positive

but direct-

signs of a hemolytic antiglobulin test.

process are never In hemolytic disease

due to anti-A, the that the direct antiglobulin stratiout that the mothers A has The
nosis strated the

diagnosis test serum

is made far more difficult by two facts: first, may be negative; and second, that the demoncontains anti-A and the infant belongs to group observations
newborn which are due to

by itself present
of hemolytic that there

little paper
are

significance. summarizes
disease
two

on
of value

11 infants
anti-A was

in whom made. It

the

diag-

of the
signs

is demon-

in establishing

the diagnosis:

presence
of

of a hemolysin

in the
cells.
CLINICAL

mothers

serum

and

of a raised

osmotic

fra-

gility

the

infants

red

MATERIAL

Seven

infanits

(Cases of (A infant infants also obtained. be

A 1 to birth. given In was group be who

A 7) birt-h all

were infants to

first infants

tested (A 8, suspected

because A 9,
a

they A 11) of having

h)ecame were tested found hemolytic

jaundiced because disease in its process.

within their of the mothers In

twenty-four
mothers newborn; senunt every that hours were destructiont case due Several of found life to had during the

hours
previously 1 infant

Three

and

10) was tested

A

because
11 infamtts and become Although the the

pregnancy. anti-A other were to was could

a potent there was

mother unusually in making

hemolysin

was

evidence of a hemolyt-ic group 0; no incompatibility

jaumidiced during cases evidence in such the the of first infants increased cases

other
forty-eight red red is discussed.

than

demonstrated. had with most serum, of these Ito cells cell

imtvestigat-ed.

incompatible

mothers of

The

difficulty

a diagnosis

Several groups of nonnial infants were tested: first, to define the range of the osmotic fragility of the red cells in mtormal infants (luring the first week of life; second, to see whether any of the signs observed in hemolytic disease of the newborn due t-o ant-i-A were detectable iii al)pareittlv normal group A infants with group 0 mothers; and third, to provide control observations on the strength of the reactions of group A cells in newborn infants, compared
The was with those in adults. osmotic fragility of determined, the School, Medical London, November for the red cells of 9 infants with hemolytic disease due to anti-Rh

also From

comparison. Councils 12, 1952; England. accepted D. J. R. P. It amid care. OBrien, Tizard of is a pleasure Obstetrics for publication December 15, drawing us the 1952. our constant Medical attention observahelp School of the of to Blood Transfusion Research Unit, Postgraduate

Research W. 22,

Medical Submitted

We should
T. some tions Londont. P. Mann, of these on infants

like
J. A. cases of

to G.

thank
and Drs. their Health

Drs.

M. A. Arthurton,
and and

Josephine
C. to at Upjohn for acknowledge the S. Yudkin

Lord,
for inviting

D. de ha C. MacCarthy,
to make

McSorley,

under Child

Departnientts

Postgraduate

620

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CRAWFORD,

CUTBUSH

AND

MOLLISON

621

I\/I ETHODS
BlOOd
Venous

Samples
samples external were used for vein. all determinations; blood

was

usually

obtained

from

a scalp

vein

or the

jugular

Hernatologic Hemoglobin using Ilford

Tests was
determined with a grey as oxyhemoglobin, screent of known on ittethod with cases, the by either optical in a photo-ehectric as a standard, blood of radius by also Dacie.3 and prepared stained from with fresh oxalate of spherocytosis. spun in colorimeter or Wint in the robe

M.R.C.

filter 625, Photometer.2

density

Packed cell volume (P.C.V.) was detenmine(l hematocnit tubes for 30 minutes at 3000 R.P.M. Reliculocyte connie were determimied by thte
Blood films were with
0.2

heparinized described Winitnobes films presence were

in a centrifuge

15 cm.

prepared

from

blood In to was by the NaCl

mixed nianty confirm

May-GrUmiwald-Giemsa

combination. anticoagulamtt, concentration ml. of plasma.

blood,
Plasma

unmixed
bilirubin
0.1

estimated
method thtani the in with ml. on

the

method
and was to up

of King

and

Coxon,4
with range the saline the of addition

modifollowsaline of being of of

fled for
ing

or

Osmoticfragiiily modifications:

was measured
hepaninized

of Parl)art citrated mixtures a photo-electric automatic as saline,7 arid then per witht At the cent blood of

co-workers#{176} used; 1.0 and per the cent-; hypotonic the

rat-her include was for then omitted, 45 minutes measured measured and are by plotting cent cent iii the fragility by 5.0 usually

solutions was complementary

centrifuged the blood to For supernatant and saline deliver

extended
solutions standing solutions solution

to

concentrations in a water-bath

blood at pipets

after

23 C. and colonimeter; (based

color the

densities quantities designed fragility

were 0.04

on Wright6) corpuscular

approximately conciseness, this in the was various range points the results deduced

respectively. expressed arithmetic the median paper t-he best off the fitting reading lysis probability the percentage line to saline used of of an of of 0.434 at with by thte intervals au S.D. method tested per over of 0.008. original by described to the hysis the

(M.C.F.);
found points tion to M.C.F. When anti-A,

in the corresponding

concentrations 0 t-o 80 per to 50 per falling osmotic

of hvpot-onic inspection,

straight

concemttra-

lysis.

In the
raitge of art 20

cases
to 80

of hemolytic

disease
were disease 1)100(1 blood fragility one M.C.F. adult-

of the newborn
deduce newbonni, newborn

due
the

only (see testing

results). infant timne. conveniemtt ntethtod little ntomtt tested of 0.433 method obtained produced adult M.C.F. The anti-A globulimi vaniationt. his had per used twentty-five cent was in hemolytic first, to use osmotic Thus, a mean NaCl rabbits times a modification8 the the

a control

sample
was used, beemt

was always
tested adult before. showed

tested
With relatively

at found

thie more this

sante

of a normal

infant
frequently any

hut later it was

adult
the red

who
cells

had of

particular

twenty-five cent NaCl a perio(l

times
with

at intervals
au S.D.

over

a period
and a second red were powdered cells. used:

of elevemt

of 0.009

of thirteen
Survival met-hod. Morgan,9 Two

months
of transfused auttisera anti-M and

had a mean

of Ashhys

commercially.8

Serologic
Direct cases strongest were due tested (Al,

Tests
antiglobulin A 2, A 3, and reactions against with serial test. The A 7) the

test

was

carried serum cells.

out

as was

descrih)ed used serum. at

by a dilution

Molhison.b0 which

In gave

four the

antiglobulin of group the of the by

Rh-sensitized dilutions

In
infants

tlte

remaininig
wit-h hemolvtic

7 cases,
disease

the

infants
of the

cells

antiglobulint with t-he

Detection
to anti-A,

of free
and

anti-A.
of ten

The serum
control

newborn against

A infants

group

0 mothers,

was

tested

adult
8

A, cells,

first,

in saline

and
Ne-

secon(1,
York.

indirect

antiglohulin

test.

From

Lederle

and

Co.,

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622
I?eactivity hemolytic adults absorbing indirectfrom A and of infants disease normal a group antiglobuhin a group substance A secretor. in saliva. titrations. of the infants. 0 serum test,

HEMOLYTIC

DISEASE

OF

NEWBORN

cells

with The with using

anti-A due tests A2B an was used

The
were:

reactivity
was compared by serum test-ed thatof of added of the a a low A, her agglutination

of

the

red with by an

cells that
a

of the of cells serum,

infants from prepared serum; with by some from and

with normal by an saliva Race cases A, To serum as this of the the a

newborn

to anti-A cells; immune obtained used the

hemolysis anti-A and was cells titer were from

an

immune

anti-A neutralized

partially by the

Saliva The

method previously.

described In as those as serum, the highest the account

and

Sanger.2
method against described own infantwas a volume The donor reciprocal been convent-ion, taken neutral throughout

Isoagglutinin

the mothers
and serial, and source donor hemolyse the testvolumes dilution second A2 adult-s. Detection halving second of belonged

serum
of

was tested The

of the of a 5 per was group Hemolvsin more and This serum 0;

as

well

a heunolysin. dilutions

hemolysin
test cent serum are a trace test cells from serum drawn had suspension

a serum first cells. same

determined of fresh

follows: added work; dilution dilution, so that

neutral

a volume complement, to A, cells. serum of of neutral

freshly her titers than of

agglutinin

titer
In calculating

(16) and did not itself

of the imito

expressed of lysis have t-he usual

as the occurred. both

in which

t-est

serum the

in the volume

first
differs

tube

of t-he titration suspensiont and

is considered considering the

as 1 in 3, that
isoagglutinin

in the first
that

tube as 1 in

as 1 in 6, etc. 1.

in expressing

titers,
tube

of ignoring

of cell

dilution

in the

Indirect described
from her

antiglobulin previouslymu;
own infant

test using partially neutralized serum. The niet-hod used was in a number of cases t-he mothers serum was tested againstas well as t-hose from A1 and A2 adults.
RESULTS

cells

Most of the flndiuigs in the 11 infants due to anti-A are set out in table 1.

with

hemolytic

disease

of

the

newborn

The

Mothers Only

History
in

1 mother (A 5 and stillborn

(A

the but

series had apparently had

and in

had

not

previously

been

pregnant

(A had disease
with

2).

Two

mothers who
newborn

A 6) had

normal not previously

4

infants affected
given

and wit-h
birth

2 others hemolytic
to infants

had

infants of the
an un-

were

The
usual

4 and A 10). remaining 0 mothers

degree of jaundice

of these 6 a diagnosis of hemolytic disease of the newborn due to anti-A had been made (A 7, A 8, A 9, and A 11). None of the mothers gave a history of having had injections of bacterial vaccines Hemoglobin Of values or toxoid or anti-serum.

Concentration whose and cord blood was tested, 3 (A 1, A 8 and A 11) had 1 (A 9) a low normal value. (The range of hemoglobin was taken as 13.6 Gm./100 ml. figures to those of other authors after birth, 3 (A 2, A 4, and remaining 4 (A 3, A 5, A 7, range. (The hemoglobin

the 4 infants below normal

concentration of t-he cord blood of normal infants to 19.6 Gm./100 ml.3 The relationship of these has been discussed elsewhere.#{176}) Of the remaining A 6) had values and A 10) had 7 infants below the values in the

first tested some hours normal range and the lower half of the

normal

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CRAWFORD,

CUTBUSH

AND

MOLLISON

623 the first two to three

concentration days Mean The mately M.C.H.C. of life was

in venous taken as

blood 14.5

of normal to 22.5

infants

during mi.4)

Gm./100

Corpuscular mean 32 M.C.H.C. per often

Hemoglobin
in normal

Concentration newborn

(M .C.H infants has

.C.) been found to he approxianti-Rh, because

was

cent.5 appears includes

In

hemolytic to be lower a significant 3 there

in he higher

disease of the newborn due to than in normal infants, presumably

proportion of nucleated, M.C.H.C.

the

cell

column cent.

non-hemoglo-

binized red cells. Thus 30 per As

born shown due

in table 1, M.C.H.C.

are
the

3 infants
cases

whose

below
newthe of ap2

in table
to anti-A

of hemolytic normal.
and

disease be noted M.C.H.C.

of the that

tended

to

than

It- will

cases with proximately Reticulocyte In

from

the highest osmotic 36 per cent. Counts laboratory,

7 per cent
reticulocyt-e

fragility

(A 4

A 6) had

an

this
2 to

count-s

in days

normal of life

infant-s and to

are be

found less

to range than 5 per

during

t-he

first

two number

cent
the 8 to

from
present 21 per

the
series cent

third
had on

clay
an the thirty-six

of life
increased first day hours

onwards.
of life normal of life and

By

these

standards
diminishing from

all
values

the

infant-s
from

in
In

of ret-iculocytes, gradually group ranged

ranging thereafter. cent.

the values Blood

cont-rol

series
first

of 10 apparently

A infants

with group 2 to 6 per

0 mothers,

in the Films

Erythroblastemia.

Of limit
was

9 infants of normal.

examined
per films 100

within W.B.C.-a

forty-eight

hours

of birth, which

had

30 nucleated

red cells or more present

was

proportion

is well disease A 11.

of

above

the upper
and
6 and

Spherocytosis

in the

of all

11 infants

with hemolytic A 4, A 6, A 10, and

during the third

due to anti-A
In Cases A

particularly
11, spherocytes

striking

in Cases

-ere still present

week

life. Blood films of 6 of the 9 infauits showed doubtful wit-h hemolytic disease due to anti-Rh were also examined. second infant R 4, R 5, and
Jaundice
and

Only 1 case (R 9) show-ed R 7) show-ed

Plasma Bilir-ubin

a striking degree spherocytosis;

of spherocytosis the remaining

(R 1); a four (R 3,

no spherocytosis.
Concentration One
concentration

Cases A 1 to A 7 were first- tested because of early jaundice. became only slightly jaundiced, the maximum bilirubin 7 mg./100 ml. In the remailiing 6, t-he maximum bilirubin

infant-

(A 1)
being

concentrations
infants, developed history anxiety

reany

corded
was signs felt

varied
because of damage

from
to

of the

11 mg. to 26 mg./100 ml. dept-h of the jaundice

central nervous system.

In
but

some none

of these of them

the

Amongst

logic

the cases tested findiuigs (A 8 to A 11),

because of the mothers previous only 1 (A 9) became jaundiced.

or

ser-

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624

HEMOLYTIC .
C
..-32

DISEASE

OF

NEWBORN

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From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

CRAWFORD,

CUTBUSH

AND

MOLLISON

625

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eq

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From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

626 Osmotic
Normal infants,

HEMOLYTIC

DISEASE

OF

NEWBORN

Fragility
infants. expressed as The results of osmotic fragility measurements in

normal lysis and

the

concentrations are summarized disease, the normal

of NaCl
in

in which

50 per

cent

5 per
infants

cent- lysis occurred with hemolytic

table 2. For comparison range of 50 per cent lysis

with the and 5 per

cent lysis, calculated as Mean 2 S.D., group of normal adult-s has been included teen infants tested at two to twenty-four blood
fants

is shown against each age group. A for comparison. The group of sevenhours includes 8 infants whose cord at two to five hours, days
but does three
occasion,

was whose
of the
in

tested
blood infants
infants every

; the
was

group tested
cord

of infants at two
blood was

tested
tested.

includes
not to five

4 ininclude hours

to twenty-four

any

whose
were case

Eight later;
change

tested at birth (cord blood) and again the M.C.F. was lower on the second
per cent NaCl.
Fragility
50% Lysis S.D.

the

mean

being

0.011

TABLE

2.-Osmotic
,

of Red
(M.C.F.)

Blood %
NaCI

Cells in Normal
I 5%

Infants
Lysis
S.D.

% NaCI
Mean 2 S.D.

Age

of infants

ce - Mean
-

I Mean

2 S.D.

Mean 0.502 0.486 0.474 0.475

Cord
2-24 2-5

blood

16

0.422

I 0.021

0.380-0.464
-

0.022 0.022 0.019 0.012

0.458-0.546 0.442-0.530
0.436-0.512

hours
days adults on .Thi.C.F. blood hours vs. vs. vs. 2-24
2-5 2-5
-

17
14 18

0.408
0.395 0.424

0.015
0.016 0.010

0.378-0.438 0.363-0.427 0.404.444

Normal tests Cord 2-24

0.451.499

hours,

p =

0.07;

Cord
The which

blood
observations

days, p days, p
n the

0.04;
<0.01.

normal lysis is

infants

are
against

also

presented

in

figure

1,

in

average

percentage in
saline

plotted

NaCl

concentration.

It

will con-

be the

noted M.C.F.
The

that
of was

the
is

centrations

three that
iui these and

age groups, the percentage expected from extrapolation

age-groups mothers normal were were group
chosen

lysis in the of the line

at random determined. It whose and

higher from

which

deduced.
infants infants the blood thought their not was mothers

normal of the to

groups advisable known lysis values

test

some

apparently

A infants

were hours
cent; all

to be group
occurred thus in being

0. In 10 such varied
well within

infants 0.387
range was be

tested
ranging found

betw-een
from in 0.477

tw-o and
to

thirty-six and

after birth, M.C.F.

NaCl

from
the

to 0.417 per cent NaCl,

unselected to anti-A.

5 per cent

concentrations

0.5 11 per infants.

Infants Cases
method nitely co-workers,5 within

with
and

hemolytic
the

disease fragility
can results limit-s.

of the newborn measured

compared

due
with in

(See
found

table
by the

1.)

In and

A 3 to A 11 osmotic
in normal normal infants

by the Case
above

method the

of Parpart findings

those the

same

(see table Fragility

2).

Only
was just

A 9 were
upper

defi-

limit

of normal

From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

CRAWFORD,

CUTBUSH

AND

MOLLISON

627

in

1 case

(A 3),

was

only

slightly
in

increased
4

in

3 (A 5, A 7, and A 11).

A 8), but- was for of 16 alid

hours limit of

moderately

or greatly

increased

(A 4, A 6, A 10, and osmotic were became within normal normal

In 6 untransfused

infants after birth,

cases

in whom

fragility changes at some method

more

were followed limits time at the

between

one
and

week
in

or more
two

the

results

age

1 week

(A 3 and

A 5) and

51 days in the other The first 2 infants (A

It series may be

4 (A 4, A 6, A 10, and 1 and A 2) w-ere tested

that by infants for tested
0-0

A 11). by the
infants

of Dacie
than a few upper

Vaughan6 old the upper in a small

assumed

normal in this

limit of the M.C.F. of normal

this method

is less than laboratory7

CORD 2-24
2-5

0.40 per cent since the

BLOOD HOURS DAYS

I-.

X-X 90

Sc.

50-

I)

jz,
0

IC
S

01

030

0-40

t
red to cells iii

0-50

060

070

NoCI.
of normal table 2. Each NaCl infamits point (luring on the the chart first Percentage five is the days average lysis is of

FIG.

1.-Osmotic 3 groups lysis on a scale of are

fragility those red arithmetic the of

of the referred cells

life.The
percentage plotted

imt amiy probability.

particular

concentrationt.

M.C.F.

for

cord

blood tested

was

found was found

to

be
one to

0.405
be 0.36

per
per

cent
days cent

NaCl,
XaCl.8

and
In

in

another

series of infants limit of normal

by

this met-hod

to seven

after l)irth, the upper

for M.C.F.

Case

A 1,

the M.C.F. and in Case siderably

To infants Figure
adequate

at the age A 2 at the

osmotic hemolytic t-hat

of 15 hours was 0.42 per cent NaCl (slightly iutereased), age of 23 hours the M.C.F. was 0.46 per cent NaC1 (confragility disease expression auid
of lysis

increased). summarize: with 2 shows was of the outside due in results normal to the limits anti-A. in 10 out of an 11 of the

newborn

terms

of M.C.F.
from

gives 0.55 per

in-

idea

In particular,

of t-he findings the amount

underestimates in concentrations

departure

normality.

of NaCl

above

cent

From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

628
was

HEMOLYTIC

DISEASE

OF

NEWBORN

much curve. Infants

in

greater with

than hem-olytic
are

that disease
shown

expected

from

extrapolation

of

the

upper

part

of

the
ings

of the newborn
table

due

to anti-Rh.

Some
antiglobulin

of the
test

findwas below

9 infants

in 9 infants

moderately
normal limits.

or

strongly
Six of the

positive

and
had

3. In all, the direct all had hemoglobin

a hemoglobin
venous cases,

concentrations

concentration blood nine

of less than

10.5 Gm./100 one case) and

ml. must

(cord blood be regarded

in 5
as

hours

after

birth

in

a severely

affect-ed

group.

x-x

OBSERVATIONS OBSERVATIONS

IN IN

CASE CASE

A6 A9

I)
In

030

0.40

to Fn.. 2.-Osmotic fragility in respective each in case, Cases the 9 infants

NoCI.
with except on hemolytic in only at A 10; Cases one age disease of and the A9, sample newborn due to

anti-A.
are points at- age A4,

Percentage
against omitted. are

lysis
their In

is plotted

on a scale
curves; estimations

of arithmetic

probability.
A6 blood

The
the

case
are in

numbers
viz: A 3,

marked

experimental shown, Cases

of 3 to A5,A6,andAll.

14 hours

A 7, A 8, A 9, and

of 2 to 3 days

Osmotic fragility w-as normal limit of normal in 2 cases (R hours (R and 1 and R 3 at R 9).
the The

in 3 4 and hours)

cases

R and

6);

(R 5, R 7, and just raised

figure

in

R 8); was 2 cases

near the upper (R 2 at three in only 2 cases that

is that

thirty-six
results

considerably
in

increased 3. It will
saline

are

plotted

be observed
solutions

on
ex-

the whole pected In anti-A from none

percentage

lysis in the of the upper wit-h red a raised cells

less hypotonic part fragility and the

extrapolation of the 4 cases the infants

of the curves. was mothers there incompatibility serum. due to

between

Survival
In obtain

of Transfused
2 cases, evidence transfusions about

Cells
of group the specificity A and and group severity 0 cells were hemolyt-ic given in process. order to The of the

From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

CRAWFORD,

CUTBUSH

AND

MOLLISON

629 19 During

findings following

in

Case

1 have more

been than

reported two thirds

previously.0of the A cells

the
eliminated

six

days
w-hile

transfusion,

were

the 0 cells
TABLE

survived

normally.
Fragility Measurements Newborn in due

3.-Osmotic

9 Severe
to Anti-Rh

Cases

of Hemolytic

Disease

of the

I
No of

Present infant

Osmotic
-

fragility

..
Bunrubin mg./ 100 ml.

1
&m./

% NaCI
NucI. r.b.c.

Case
no.

I I

previ siblings

Age at time of - examinaB.Wt. tion

m - -

H,,C.

Retic.

100
-

I per

50%
(C

- -

Sex

i,

- w.b.c.

F.)

Ri Pag. R2 Cha.1

M18/0

Cord blood

9.0

32128
-

35

400

0.5100.638

2
-

F
1

7/14

Cord

...
I

9.4

1
-

31

30

...

25

0.453

0.523

blood 3 hr.
9hr.

1 14

12.0 9.61

39 34

31

...

...

0.455

0.519

R3

M7/10

28

...

200

0.4310.534

Coo.,
R
Rio.

36hr.279.1129i313411800.4410.560 1 M
i

6/14

Cord blood 3hr.1

5 718.4 5
I

9.6

28
-

34

...

I I

.-.

26132...I

...

0.4400.496

0 I
I

6/10

Cord

10.2
11.9

32
1

32
...

1 20

60

...

Lan.

blood 1 hr.
17 hr. 2 days

I
I

6 14
21
... I

...

I 0.428

0.496

11.8
10.0
10.2

39
33
34

30
30 30
30

24
32
...

95
15
...

0.421
0.413

0.490
0.490

R 6

7/1

Cord

Fos.

blood1
3 hr. I
...

12.5

42

...

...

0.44() 0.425

0.507 0.518

R7 Dua. R8 Hoa.

6/10

Cord
blood

...

11.7

40
I

29

19
I

67

F8/0Cord

313.03735

7 I -

blood
9

hr.

...

...

T_Ii
... ... ...
-

I 0.431

0.501 0.565 0.564

R9 Lak.

0 I
-

M
-

7/7
-

Cord
blood
3

...

113.2

...

0.480 0.480

hr.

...

15.6

50

31

...

400

R 3 and R 5 were
of life or later; the

treated remaining

with A.C.T.H. infants were

or Cortisone treated by

and transfused on the exchange transfusion.

second

day

In
fants

Case

A 6 a transfusion
had

was

given

on the
both was

ninth A1 and still

day

of life

because

the

in-

P.C.V.

fallen to 32 per cent;

0 cells active.

were

given

in order

to discover

whether

the hemolytic

process

Carefully

measured

From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

630 amounts during the of blood subsequent were

HEMOLYTIC

DISEASE

OF

NEWBORN

transfused five weeks.

by The

scalp

vein

and were

samples corrected

were by

withdrawn the factor

estimates

Body
Body to cells bers number allow in the transfused of A for changes in blood

weight weight
volume.

on day on day
The

of_estimation of transfusion
survival the exactly found those 1.08). of relative the expected However, transfused numbers from the cells of A and numthe thereafter is

shown

in figure
infants

4; on
(ratio

the
A/O:

day

after
were expected

transfusion,
almost 1.07;

circulation

cells rapidly

diminished

so that

within

the

following

eight

days

X-X

OBSERVATIONS

IN

CASE

RI

01

030

040

050

060

0-70

080

to

NoCI.

Fw. 3.-Osmotic fragility in 9 infants with hemolytic disease of the newborn due to anti-Rh, tested within mtine hours of birth (cord blood in Cases R 1 and R 7). Percentage lsis is plot ted on a scale of arithmetic probability. The case numbers are marked agaimtst
their respective curves; except in Case R 1 the experimental points are omitted.

approximately eliminated Direct

In in no The globulin glutination
from

60 per at the

cent

of them rate

were

eliminated.

By 1 per

contrast cent

the a day.

0 cells

were

expected Test
11 cases test value was of

of approximately

Antiglobulin
7 out case of the did serum of the

the testing

test

was the

positive, aft-er cells the against

though first

the seven

reactions days of dilutions was serum

were of life. of

weak; anti-

remain

positive

possible

a range

the 1/1024,

demonstrated infants cells the maximum the same

in Case A 9. Although there with dilutions of antiglobulin agglutination serum

was

some
ranging

agof

1/4 By

to

observed

at a dilution

1/256.

contrast

antiglobulin

gave

maximum

agglutination

From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

CRAWFORD,

CUTBUSH

AND

MOLLISOX

631
weakly sensitized with

at

a dilution

of

1/32

when

tested

wit-h

Rh

positive

cells

Rh

antibody. In 2 of the 4 cases in which

eliciting any trace

a negative
(A

result is recorded,
6 and A 11).

the cells were tested sera,

against a range
without

of dilutions (1/4 to 1/1024)

of reaction

of tw-o different antiglobulin

Spontaneous
In fant flow Cases formed

Clumping
A 5 and large

of Whole
A 6 it was which

Blood
observed were easily thatseen on blood freshly draw-n from was tile. In the in-

clumps

when
an

the
opal in

blood
glass Case

allowed Case
was

to
A 5
st-ill

the

down the side of a tube or was clumping had become weak by

examined the fifth

day

of life;

A 6 it

E E
U
B

0.
4

400000 B
1.)

-u
0

2o#{243}poo
C

I-

I-

0 0 z

Doys
FIG.

Aftir
group two weight

TransfusIon
0 cells, types during transfused of cells the were period to Case transfused. of observation. A 6 nimte days The estimates after

4.-The approximately been corrected

survival equal for

of group numbers changes

A and in body

birth; have

of the

demonstrable seventeenth
cases in this

on day.
series

the fourteenth The phenomenon

but
it was not

day

of life but was not may well have been looked for and

demonstrable present in was not

the

on the other

specially

noted.

Free In

Anti-A 8 out of 11 cases, adult A 10.

or hemolyse

the

infants

serum,

collect-ed

within

the

first

three it- would

days not

of life,
agglutinate

sensitized

A1 cells to an antiglobulin serum although A1 cells. No free ant-i-A could be demonstrated

in Cases

A 3, A 6, and

In the control
3 cases in which

group
the

of 10 normal mothers serum

A infants wit-h w-as capable

group
of

sensitizing

0 mothers, there were A, cells; in 1 of

From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

632 these
cells

HEMOLYTIC

DISEASE

OF

NEWBORN

3 cases
gave

the

infants

serum

sensitized
test.

A,

cells

although

the

infants

own

a negative

direct

antiglobulin

Reactivity
Control

of 4 Cells
group. apparently normal group adult A donors. infants The were tested

firstly A serum,
shown

with
in

an a serum
parallel

and
with

secondly
Ai and A2

with
cells

a partially
from

neutralized

immune
results

antiare

in table

4. among
and

Note
were globulin only

that
test

the cells
among

17 infants reacted
the 9 infants

whose
whose

cells

were
cells

agglutinated A1 cells
w-ere notin the agglutinated

by

ai,

there antiby a

4 whose 6 whose

as strongly even more

as adultweakly

indirect

there

were

cells

reacted

than

adult

A2 cells.

Further evidence of the weaker from hemolysin tests. Among the

group

reactivity of the infants cells was obtained 10 apparently normal group A infants with
cases in

0 mothers,
A, and were A2 adults w-eakly

there
but agglutinated

were
failed

2
by

which

the

mothers infant,

serum

lysed the

cells

from cells
TABLE

to

lyse an

those a1 serum.

of the In

although 2 cases

infants

the

same

the

mothers
Serum

4.-Reactions Compared

of Group A Cells of 26 Normal uith the Reactions of A,

Reaction with immune
-

Infants

and
anti-A

A2

with- an Immune Anti-A Cells from Adults

antiglobulin test)

Reaction with a serum

serum (indirect with adult cells

compared

____________
=A, I <A2

=A,

>A2

17 9
*

+*

4
1

I
-

7
0
-

2
2 cells.

4
6

0 reactions were always

These

weaker

than

those

of

adult

serum

gave

a strong

indirect

antiglobulin
newborn

test
due

with

adult

A1 cells As were

but

failed

to

sensitize the infants Cases of hemolytic cells from 10 of the days of life and

cells. disease of the 11 cases were 10 failed

to anti-A.

tested to react;

with

an

a, serum 4 who

show-n in table 1, within the first few negative at birth had A 9)

2

4 of the

of the

(A 3, A 8, A 9, and A 11), 3 were re-tested later. In Case A 11 the reaction already become positive at the age of 2 months; of the 2 infants (A 8 and tested
Thus, infants

at the
in

age of 10 months, all, 8 infants could could not be classified the

w-it-h

one be
since

was

now positive as (Case

but the other

still negative. remaining

classified
1

A1 and 1 as A2; the A 2) was never tested (Case A 3).

its mothers

with
serum

an

a,

serum
compared in all

and

other
those that

was
from wit-h

tested
adults titer adult

only
of when A2 cells;

at birth
group the the

In 6 cases, the reactions 6 cases than, the hemolysin

of the infants

red cells with

w-ere

A1 and
infants results of

A2 (see
cells were indirect

table
used

5). Note that was as low as,

tests

or low-er

antiglobulin

also

demonstrate
of A

the
Substance
were

low
in

reactivity
Saliva
of

of the

infants

cells.

Secretion All

11

infants

secretors

A substance.

From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

CRAWFORD,

CUTBUSH

AND

MOLLISON

633

The
All anti-Rh

Mothers the
itt

Serum belonged serum. characteristics to group of the 0 ; only anti-A 2 -ere in Cases Rh negative and
neither had

mothers her of the

Some

A 3, A 4, A 6, A 9, A 10,

and A 1 1 have already been show-n in table 5. Table 6 show-s the isoagglutinin titer in saline and the hemolysin titer of samples from all 1 1 mothers, with a record of the time before and after delivery when the samples were taken. Although all cases antiglobulin
in most instances

the

isoagglutinin of lysing

titer A, cells

was and

not

exceptionally them

high,

in

the

serum serum.

s-as capable

of sensitizing

to an

TREATM

ENT

There

were

infant-s

in

whom

the

diagnosis

of hemolytic

disease

of the

new-

born w-as made w-it-hin A 10, and A 1 1). Cases Cases

TABLE

the first twenty-four hours of life A 1, A 10, and A 1 1 did not appear
no Cells
A
m

(A I , A 2, A 7, A 8, A 9, to be severely affected; a simple

due

A 10 and
5.-Reactions
(om pared -with

11 received
of
those

treatment; in and
titer
-

Case
of in

A 1 received
Hemolytic
Tests
antiglobulin
-

transto Anti-A

Infants
of
I

6 Cases
A
2

Disease
the
test
-

Adult

Cells,
indirect
-

uith

Mothers

Serum

Agglutinin Case
flO
_

titer A2
Infants
-

Hemolysin
-

I
A1 cells
-

Reaction
wuth

of infants
a

cells

A1
cells

A, cells

Infants cells
-

A
,

II

A2 cells

Infants

serum

cells

cells

cc

I cells

A3

256
1 1024

128 128 256 2048

128 256
51260

12
12

6
12
-

6 12 6
18

+++ +++ +++ +++++(+) +

++
...

(+)
...

A4 A9
A 11

A6256256256
512

18l2,
48

(+)(+)
w
+

A101024I256512I 8192 2048

181

6161

(+)
+

24

12

12

++

0 + + 0 + 0

fusion at from another maining

of group three hemolytic

0 and
cases disease (A

group
received of the

A blood,
a simple newborn

as already
transfusion

described.
of group

hospital),

Case A 2, (treated! 0 blood. In the relost an infant

7, A 8, and

A 9) the due

mother to

had
anti-A,

previously

and

it was

thought
suspension

deof

sirable

group
four mildly were fusion; effect was day described,

carry out exchange 0 red cells, to which had

the 4 cases of life, to of these its hemolytic twenty-four a transfusion no although be too in

to

transfusion been added the

was infants when given although after starting

using AB

a concentrated
substance.

Amongst hours

w-hich
tw-o

diagnosis
given first

was

made A 3 who
benefitrise in In

after
deeply from without

the

first

twenty-

treatment-

t-o Case seen a sharp treatment. of group to

appeared
exchange any reticulocyte

to be very
they transobvious count already the ninth

affected; considered one on not-ed of life. Progress

(A 4 and
a course

A 5) were
of A.C.T.H.

jaundiced,

old

(A 4) was
process, hours of group

the
Case was

A 6, as
given on

A and

0 blood

Subsequent Five

qf Infants who during were the not treated! by first month exchange In the transfusion 2 infants were tested A 6)

of the infants
occasions

on several

of life.

A 4 and

From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

634 who and were 9.7 tested Gm./100

HEMOLYTIC

DISEASE

OF

NEWBORN

most ml)

frequently, were observed

the

lowest

hemoglobin and twenty-two

concentrations days

(9.9 after birth

at sixteen

respectively;
TABLE 6.-Agglutinin

both

infants
and

showed
Hemolysin Disease

a spontaneous
Titers due of the

rise
Mothers

thereafter.
Serum

In
in Cases

the

remain-

of Hemolytic

to Anti.A
Tests with
-

A, cells Hemolysin

Case

no.

Days

after

delivery
-

Agglutinin

titer

titer

Al +10

512 512

6 12 12 30 12
12

A2

+1

64

+7
A3 +4

2048 256

A4

+2
+9 I

256
1024

12
A5 +3 256

6
12 18 24

+30
A6
-

512
256

+2

+12
+20

1024
1024

24
12

A7
I

0 +7 -50

256 1024

24
18
120

A8

256

0
+10
I

1024
256 128 2048
512

120 72 60 60 60 48

+120
-30

A9
-

+1 +5

2048

AlO

-60 +1 +12 I 1024 1024

18 24

All

+10

2000

+2
+15

I
I

8192 2048

24 24

ing 10.3

3 infants Gm./100

of this ml.,

group but these

(A 5, A 10, and infants were

A 11) tested

the less

lowest frequently.

value

recorded

was week of were

No infant life. Moreover recorded normal

in the series developed signs of kernicterus during the first the 2 infants in whom the highest bilirubin concentrations at the age of 6 months and appeared

were seen again (A 4 and A 5).

to be entirely

From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

CRAWFORD,

CUTBUSH

AND

MOLLISON

635

Suspected

Cases earlier, of the infants were had found no signs fragility. only is significantly
21

As mentioned lytic These ever disease were they

many

infants

were

seen

in whom

the

diagnosis

of hemo-

new-born due who became to belong of increased It appears examining more diagnosis the

to ant-i-A jaundiced to group red that large cell

was suspect-ed but not established. during the first twenty-four hours to have group and 0 mothers. no increase How-in red can be

of life and cell osmotic demonstrated patibility infants.#{176} lIt one

was

A and

regeneration

by

the role of anti-A in these cases groups and showing that anti-A than
in a control

incom-

frequent of hemolytic mother had

group new-born
an

of non-jaundiced due to anti-A apparently signs of a

infant cause. process:

the

disease previously failed

of the lostto reveal

suspected this

because However,

infant,

from

investigations

unequivocal

hemolytic

Mrs. Ds first infant ened and the infant

became
was

jaundiced to at- the was he very age no Twelve

at

the anemic

age

of 12 hours. and The the the after present the to have mother infants

The nucleated was authors

jaundice red

rapidly blood to be was months infant, group

deepcells notMrs. in 0, deD later;

found

the peripheral
Rh

blood.
but her could

It died
serum

of 31 hours.
Rh

found
group seven first

negative Rh antibody

contained

antibody; by months

blood of her

termined.
no

The

mothers

serum
be detected.

examined

birth

became pregnant again; during the last few weeks of this pregnancy her serum was examined once more; no Rh antibody was found but the serum hemolysed A, cells to a titer of 12. The infant was born at term; cord blood findings were as follow-s: group A,, Rh positive; direct antiglobulin test, negative; cord hemoglobin concentration, 20.5 Gm./100 ml.; reticulocyte count, 6 per cent-; film, 50 nucleated red blood cells per 100 white blood cells, suggestion of
spherocytosis; ml. The number of nucleated other from findings ml. red cells were and peripheral all the in the within infant blood peripheral normal never after blood limits. became forty-eight osmotic fragility-M.C.F. 0.438 per cent XaCl.; plasma bilirubin, 2.3

mg./100.

was
The

suggestive peak hours. hilirubin The

of a hemolytic concentranucleated red

process
tion was

hut- the
only disappeared

4.0 mg./100 the

jaundiced.

cells

This of disease who has anti-A.

case

is of interest

in showing

that

a group

A infant contains disease,

with

no

definite

signs

can be previously

born to a woman lost an infant

whose serum from hemolytic

an a hemolysin presumably

due

and to

DISCUSSION

Much (or anti-B) of 11 cases the features Signs

of the has

previous been

work

On hemolyt-ic

disease

of the

new-born

due

to anti-A on a study emphasizes

in which

of the

review-ed elsewhere.#{176} The present paper, l)ased there were definite signs of red cell destruction, fully developed syndrome. Cell Destruction
w-ere consistent

of Increased

Red

The findings in all cases hemolytic process. Although the normal range, thatthese red cell of reticulocytes. It appears

with those
infants

of a mild had an increased

or

moderate

4 of the like

11 the

had

hemoglobin

values

within
number

4 infants,

remainder,

destruction

continues

for a shorter

time

after

birth

in

From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

636
cases curring due to two anti-A to four than

HEMOLYTIC

DISEASE

OF

NEWBORN

it does after

weeks

in cases due to anti-Rh, birth was not noted

since
in untreated

severe

anemia
cases in

octhe

present series. However, 10 Gm./100 ml. in the

2 infants first three destruction appears 2 infants despite counts of the

(A 4 and A 6) had hemoglobin weeks of life and in one of these during the third w-eek of life

values infant-s -as

below (A 6) demondisease

the persistence of red cell strated. Although early jaundice due

never

to be a common (A having 10 and evidence due

feature

in hemolytic

to anti-A, became process

there jaundiced (ret-iculocyte

w-ere

A 1 1 ) in the of a moderately 15 per to anti-A

present For

series severe this preferable

who hemoreason to

lytic

of approximately newborn

cent). seems

the term icterus Osmotic

hemolytic praecox. Fragility and

disease

Changes Gasser drew attention to the presence of microspherocytes due

be

Grumbach in the blood compatibility; though newborn osmotic per the cent end they

films of 2 cases of hemolytic disease of the newborn in another case they found osmotic fragility to gave no details Robinson to be raised compared with or twenty-one of their and in 4 out 0.45 days, method and also per began no normal not-ed lysis cent beginning NaC1
in 0.48

to ABO
increased

inal-

range

of values and
in 0.63

for found

infants. fragility NaCl of fourteen

associates23 to 0.47 lysis

spherocyt-osis in normal to 0.51 per

of 4 cases,

to 0.69 at NaCI;

adults: cent

no normal range for healthy infants to be a very useful sign in diagnosing

was given. Vogel24 considered the syndrome of hemolyt-ic has been studied merit of making

spherocytosis disease of the met-hod of to obtain

newborn due to ABO incompatibility. Iii the present series, osmotic fragility Parpart and associates5 which has the great closely standardized 15 normal adults is almost males, in the cells cord agrees exactly namely with blood 0.425 t-hat results. reported the same per cent Thus in the as that NaC1. infants and

by the it possible

the median corpuscular present paper, namely found The by finding Parpart that the et al. the same does

fragility (M.C.F.) of 0.424 per cent NaCl, in 12 normal of the that red as that finding of adult show due 11 the young cells red that M.C.F. the

of normal of Waugh

is practically co-workers25--as

M.C.F.

diminishes during the first few days of life. The present observations this diminution in fragility begins within five hours of birth. In the present series of cases of hemolytic disease of the newborn M.C.F. curves born raised changes previously: increased findings The was had due above By normal contrast, limits shape of greater of 10 cases Only disease (see in 10 out figure of 11 2); the of cases
cases,

to anti-A, fragility showed newwas out

and films

in all

an abnormal

blood

of all 11 cases disease

spherocytosis.

in a series

of hemolytic

of the

to anti-Rh, in only 4 out were

in hemolytic

than average and spherocytes one extensive newborn due

severit-y, osmotic fragility w-ere noted in only 2 cases series of observations to anti-Rh has been on published

of 6 that

examined.

fragility

of the

Shapiro7 found that osmotic fragility was sometimes in severe cases (3 out of 9) but was not usually increased which association are essentially bet-w-een
in

considerably in mild casesnoted

a raised

agreement osmotic

with the present ones. fragility and a high M.C.H.C.

From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

CRAWFORD,

CUTBUSH

AND

MOLLISON

637

in

the

present

series
in adults

can

also

l)e observed
by Vaughan.2

in some

of the

cases

of hereditary

spherocytosis Direct Antiglobulin

described

Test
associates27 found the dlirect antiglobulin test to be positive on

Boorman

and

the due tenth

fourth to day

day anti-A, after

after though birth.

birth the

in a severe

case negative al.23

of hemolytic
in

disease case the

of the examined

newborn n the

test

was et

another that

Robinson

reported

direct-

antiglobulin

test was negative antiglobulin test cases and negative due rather 2 instances same serum. Free In Antibody the present
infant

n the first day of life in 2 cases. In the present series the direct was definitely, though not very strongly, positive in 7 out of 1 1 in the remaining 4. The weakness of the reactions seems to be than to the lack of antibody, test was negative the plasma adult A1 cells to
an

to some quality of the antigen in which the direct antiglobulin would quite strongly sensitize

since in of the

antiglobulin

in Infants series,

Plasma free anti-A,

in

detected the anti-A

in

by

the

indirect

antiglobulin

test

using adult Presumably

A, cells, was the amount

present of free

infants the

plasma infants

in 8 out of 1 1 cases. serum depends partly

upon the amount of antibody passing across ability of the infants cells to absorb antibody; no obvious relationship between the presence disease hemolytic could be demonstrated. of the
newborn, was

the placenta and partly upon the it is therefore not surprising that of free ant-i-A and severity of the was demonstrated and 1 to anti-A, tests by agglutinin
in

Free

antibody 1 due demonstrated

2 cases by Wiener made

of in a

disease

to anti-B

and co-workers28; medium of plasma Spontaneous

In cells

the antibody or acacia. of Red

to anti-A

Clumping case
a

Cells
described in

the
formed

due

smooth

suspension

by Wiener saline but

andl associates,28 the clumped spontaneously

infants when

suspended in plasma whole blood was noted this clumping persisted sembled that seen
in

or acacia. in 2 cases for two the blood

In the present series spontaneous clumping of and may have been present in others. In 1 case weeks after birth. The appearance closely reof group A recipients and that seen transfused in some cases w-ith group 0 of acquired

blood containing hemolytic anemia

Reactivity of Infants

potent
in adults. Cells

A isoantibody,

The

relative

w-eakness

of the

A receptor
by Wiener

in

newborn

infants newborn Witebsky

was infant and

first

demon-

strated by Kemp; has been discussed show-ed that this well demonstrated serum. acted They as weakly found as,

its possible role by Tovey3#{176}and

in protecting et

the

from

anti-A

al.28

Engasser3

relatively low reactivity of group A cells in new-born infants was by testing the cells with a partially neutralized immune anti-A that 18 out of 34 group than, A infants adult tested In by the this method work rea or more weakly A2 cells. present

From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

638

HEMOLYTIC

DISEASE

OF

NEWBORN

slight modification obtained, 14 out A2 cells. receptor hemolytic Immune In vitro. all The
in newborn

of their method was used but almost identical of 26 infants reacting as weakly as, or more weakly findings
infants

results

were

than

adult A a

present serum,

anti-A Anti-A 1 1 cases the

also show- that the can be demonstrated using adult A1 and A2 cells Serum disease capable case should of the
SUMMARY

relative weakness of the by testing the cells with as controls.

in the Mothers
in

which that

hemolytic serum
in

of the the failure

newborn of the

due her

to anti-A infants the cells serum

was in to

diagnosed,

mothers infants cells by hemolytic

was vitro disease

of hemolysing be taken newborn

It is suggested

in a doubtful

mothers

hemolyse her is not affected

as evidence that due to anti-A.

infant

Eleven only

cases

blood

group

of hemolytic antibody

disease of the newborn are described in which the in the mothers serum, incompatible with the infants (Coombs) test on the infants in 4 cases. In every case the in particular of 1 1 cases.
disease of the

cells, was anti-A. The direct antiglobulin was weakly positive in 7 cases and negative serum
with

red cells mothers A cells.

displayed fragility
those

immune was

characteristics, increased in 10 out

of hemolytic

the This

ability finding

to lyse
due

Osmotic

is contrasted
to anti-Rh.

in a series

of cases

newborn

REFERENCES
DONALDSON,

H., SIssoN,
of
1951.
WOOTTON,

R. B., KING,
VII.
P.,

E. J.,

WOOTTON,

I. D. P.,
optical data H. B., grey-wedge

AND

MACFARLANE,

It.

0.:

Determination

haemoglobin.
I. D.

Standard

for
AND

absolute
MACFARLANE,

estimations.

Lancet
2

1: 874,

KING,

E. J.,

DONALDSON,

H., S,ssoN, of the

M.R.C.

H. 0.:
Lancet

Determination
2: 971,
DACIE,

of haemoglobin. Haemat-ology.
R. V.: 3: 248,

VI.

Test

photometer.

1948.

Knu,
& PARPART,

J. V.: Practical E. J. AND CoxoN,

London, 1950.

Churchill,
of bilirubin
GREGG,

1950.
with precipitation CHASE,
A.

Determination PARPART, of the human Technique E. red H.,

of plasma
M.:

proteins. osmotic
WRIGHT,

J. Clin. Path. A. K., LORENZ,

resistance A. F.
J.

P. B.,

J. H.,
Clin. Teat and

AND

The
1947. Tube.

(fragility)

cells. of the

J.

Investigation Capillary

26: 636,
Glass

London, HUNTER,
cyte
8

E.: Handbook of Constable, 1912.

T.: A

fragility.

DAdE,

patients
MORGAN,

method for the quantitative determination of erythroInvestigation 19: 691, 1940. V. AND MOLLISON, P. L.: Survival of normal erythrocytes after transfusion to wit-h familial haemolytic anaemia (acholuric jaundice). Lancet 1: 550, 1943. W. T. J.: An artificial antigen with blood group A specificity. Brit. J. Exper. photoelectric

J. Clin.

Pat-li.
#{176}

24:

41, 1943.
P. L.:

Mousos, Publication,
CRAWFORD,

Blood

Transfusion M., with H.: CUTBUSH,

in

Clinical

Medicine.
AND MowsoN,

Oxford, P. L.:

Blackwell
Formation LancetScientific severity of

Scientific of 2: Publicaa series of

1951. H., CUTBUSH, A iso-antibodies

FALCONER, special Blood M.: of the

H.,

im219,

mune

reference Groups

to in Man. of Blood

heterogenetic Oxford, measuring 6: 777, Blackwell the

stimuli.

1952.
2

RACE,

H. R.
1950.

AND

SANGER,

tions,

MOLLISON,

P.

L.

AND

A method newborn.

cases

of

hemolytic

disease

1951.

From bloodjournal.hematologylibrary.org by guest on April 18, 2013. For personal use only.

CRAWFORD,

CUTBUSH

AND

MOLLISON

639
Brit. M. J. 1: 123, 1949.

4 5

AND

: Haemolytic : Unpublished

disease
VAUGHAN,

of the

newborn

: criteria of
1938.

of severity. the red

AND

observations.

U DAdE,

J. V. AND and significance.

L. S.:

J. M.

The

fragility

blood
disease

cells:
of the infancy newborn

its measurement
newborn. and due To childhood. to anti-A

SHAPIRO,

J. Path. & Bact. 46: 341, Osmotic fragility of red cells

the red M.: cell to

in haemolytic hypotonic disease 185,

1951.

be

18

published. FINDLAY, L.: The fragilityof

Arch. Dis. Child. P. L. Lancet
AND

saline of

in the

20: 64, 1945.

CUTBUSH,

MOLLISON,

Haemolytic 39:

antibodies.
#{176} HALBRECHT,
21

I.:
A. S.,

2: 173, 1949. Icterus Precox. J. Pediat.

E. B.,
AND

WIENER,

SONN,

HURST, of A-B

J. G.:
sensitization.

Pathogenesis
Studies

III.

Illustrative

case

histories

on

human
1946.
22

blood
A.

and
AND

their
GASSER,

practical

applications.
ABO-Inkompatibilitaten 3: 447,
AND

Paper

No.

of erythroblast-osis fetalis. individual differences in I, Brooklyn, N. Y., July,

Morbus Haemolyticus

GRUMBACH, Neonatorum. ROBINSON,

C.:
Acta.

und

Helvet.

Paed.

1948.

23

fragility

Pediat.
24 26

0. C., IHILLIPS, R. M., occurring in erythroblastosis 7: 164, 1951.

P.:

PRYSTOWSKY,

M.:

Spherocytosis
with ABO

fetalis 1951.

associated

and increased incompatibility.

VOGEL,

Personal

Communication,

WAUGH,

T. H.,

MERCHANT,

F. T.,

AND

MAUGHAN,

G. B.:

Blood

studies

on the

newborn.

26

27

28

J. M. Sc. 198: 646, 1939. VAUGHAN, J. M.: Red cell characteristics in acholuric jaundice. J. Path. & Bact. 46: 561, 1937. BOORMAN, K. E., DODD, B. E., AND TRINICK, H. H.: Haemolyt-ic disease of the newborn due to anti-A antibodies. Lancet 1: 1088, 1949. WIENER, A. S., WEXLER, I. B., AND HURST, J. G.: The use of exchange transfusion for the
treatment of severe erythroblastosis due to der beim A-B sensitization with observations on

Am.

the
29

pathogenesis

of the

disease.

Blood

4: 1014,

1949.

KEMP,

T.:
146,

tber
1930.

den

Empfindlichkeitsgrad

Blutkorperchen
Menschen. Acta.

gegenUber
path.

iso-h#{228}magglumicrobiol. scand.

tinen
7:
30

im F#{246}t-allehenund im Kindesalter G. H.:

role
1945.

TOVEY,

study

of

the

their
295,
31 WITEBSKY,

in the E.
AND

prevention
ENGASSER,

protective of haemolyt-ic
L.

factors in hetero-specific disease of the newborn. groups

61: 171,

group
J. Path.

pregnancy
& Bact.

and
67:

The

factor

of the newborn.

M.: Blood J. Immunol.

and
1949.

subgroups

of the

newborn.

I.