From www.bloodjournal.org by guest on May 23, 2016. For personal use only.
Studies
By
M
on Erythrocytes
in Cases
of Favism
and Drug-Induced
Hemolytic
Anemia
A.
OST
acquired
pathic
and
defined
,Jews
in contrast
to the
group
thalassemia
distribution.
Only
who
have
a da.rker
light
are
after
ingestion
of fava
some
as
well
are
from
and
Sephardic
eastern,
of
(e.g.,
well
central
Gross
families
drugs
Rh
a
oriental
called
occurrences.1
following
idioand
country
from
and
or
as
this
Jews
individuals
or various
acid)
of acquired
originating
hemolytic
B0D0NYI
transfusions
consplexion
such
EVA
in
Ashkenazic
of
beans
para-ansino-salicylic
(e.g.,
Jews
History
exception
blood
show
complexioned
victims
in
the
incotnpatihle
of
is encountered
quine,
(with
Past
Acute
AND
HIRSHORN
anemias
cases
Europe
destruction
this
sulpha
some
blood
population
drugs,
plasmo-
iisfectious
diseases
typhoid).
Such
distribution
factor
must
a factor
of susceptibility
be
connect-ed
could
instance
at
all
countries
western
NINA
anemia,
ethnographic
Mediterranean
SHEBA,
hemolytic
hemolytic
senzitization)
and
C.
SZEINBERG,
with
give
sulpha
the
time
To
In
his
as
he
to
the
episode
recovered
Another
aft-er
case
from
first
(or
urine,
this
she
with
the
Holy
Land
for
was
actually
known
show
known
sentence
To
family
after
one
sulphapyridine,
From
the
such
the
victim
age
of the
is that
(for
be
menstrual
after
faba
familial
accepted
1)0th
from
26,
urine
the
603
He
immi-
during
and
red
again
(allusion
the
tinged
following
she
spring
blamed
to Sarah,
of what
Mediterraneans
of fava
favism
Israel.
acute
faba.
from
and
taken
who
misinterpretation
possibly
from
1956.
woman,
in the
among
have
country,
colored
her
mention
favism
old
this
fatigue
ingestion
Tel-Hashomer,
Nov.
RBCs.
one
‘When
se abst.inuerunt.”
suffered
Hospital,
that.
we
million
of Vicia
after
occurrence
brother
1956;
times
hensolysis
an
on old women
to dispel
ingest-ion
in Roman
to
effect
task
and
could
In
red
grown
developed
extreme
very
miraculous
our
beans.
not
in
beans.
He
than
flow.
and
is reported
of fava
exposure
of a 57 year
noticed
Jew
iusgestion
apparently
then.
less
she
a second
10,
showed
season
it was
Government
Oct.
that
agent
Persian
ago,
since
fava
“Pyt.hagorei
in which
constitutional
and
to au external
the
was
years
only
hemolysis
already
this
three
same
old
faba
ate
its known
and
year
never
as
severe
a tendency
illustrate
Submitted
she
hemoglobinuria
families
what.
followed
Vicia
adtnission
spring
of Abraham)
It was
only
on
a 74
and
origin
(spring)
interpreted
down
in
season
there
came
Wife
of
blood
transfusions.
illustrating
the
she
common
disorders
exposure
matter
iso
some
of these
aft-er
crisis
country
and
second)
which
beans)
of favism
dist.rict
Iraq;
t.he
only
hemolyt-ic
suit-able
heniolyt.ic
grated
a case
first
and
arrived
in
fava
t.hat
pathogenesis
exposure.
his
was
country
place
or
t.his,
This
the
to hemolysis
drugs
illustrate
brief.
rise
of such
suggested
wit-h
a third
as
the
well-
implies.
our
and
certain
beans,
material
from
brother
a Yemenite
hemoglobinuria
from
hemoglo-
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604
STUDIES
hinuria
in
after
which
suggested
seemed
us
us
to
the
almost
ity.
The
from
the
of exile,*
In
to the
all
our
,Jews)
of
showed
prove
its
for
the
present
The
the
similar
found
in the
which
Moslem
niajor-
apparently,
maintained
particular
all
“hemolytic
of
such
well
judging
through
2000
constitution”
established
hetnoglohinopathies
associated
we
(also
Although
only
occurring
content
in
any
the
sickle-
confirm
that
non-Ashkenazic
hemoglobin,
cases
as
with
could
among
of fetal
of
of
methods
disorders.
of a significant
of Dern,
Beutler
abnormally
in
point
the
“Baghdad
in Baghdad,
w’e failed
forming
the
material
publication.
derivatives
In
beets
use
presence
investigations
starting
not
assumption
Lederer’s
he obsen’ved
,Jew’s,
has
made
major
presence
R.
brothers
sulphapyridine
interest.
of the
and
pathognomonic
erythrocytes
aniline
study
of the
and
This
of
favism)
and
this
we
of one
beans
constitution.”
Babylonians
view,
case
iuscidence
population
of
thalassemia
the
to
of
the
The
both
(probably
investigate
thalassemia
cases
racial
of the
Jews”
for
disease,
“hemolytic
of great
to
introduced
cell
a
the
point
“non-Ashkenazic
were
of
by
Jewish
is certainly
endeavor
dt’ug.
following
anetnia
origin
hematologists’
our
the
a hemolytic
I\Iediterranean
years
unknown
supported
limited
ERYTHROCYTES
developed
presence
be
Atsetnia”2,
and
of some
hemolysis
to
to
Spring
ingestion
sonic
ON
about
for
following
our
10
own
are
we
ins the past from
on representative
and
associates,
who
to
pritsiaquine
and
sensitive
per
cent
studies
of
reported
bringing
our
acute
hemolytic
samples
of both
the
a
American
in this
the
existence
number
of
Negroes3
other
served
as
paper.
investigations
anemias,
Ashkenazic
proved
on
patient-s
who
all of them
non-Ashketsazic
and nons-Ashkensazic
suffered
.Jews
control
and
cases.
MATERIAL
The
1.
subjects
sulpha
with
drugs
recovery
as
By
*
or
They
the
of
were
favism
(This
4 groups:
acute
investigated
crisis.
into
or
hemolytic
durinig
group
will
6-24
be
anemia
months
due
to
following
designated
the
throughout.
t.his
cases”).
onse
would
ins maintaining
‘‘hsemolytic
divided
were
history
hemolyt.ic
“test
insferensce
cessftnl
investigation
past
PAS.
from
report
in
of t.his
Persons
Isave
their
constitut.iots.’’
to
assume
racial
It. is left
U. S. A. among
tisat
pnnrity
to
Americmtns
of
be
tue
Ashkensazic
minsd Isave
sects
whmit
lost
will
lie
non-Mediterranseans
Jews
t.hroingh
tise
have
the
l)att.erts
origins
beets
less
generations
of Cooley’s
ansenssimi
with
intermarrying
suetheir
Medi-
terranean.
Central
and
and
though
among
only
Italians,
Eduard
name
Western
America
Moericke
FAVISM.
Europe
was
first
Greeks
to
learnt
attention
about
song
goes
favism
as
its
Er
mit
mahnt
diesem
mich
Geruch
an
die
Weg mit dieser
Bluete
Sic sagt mir, dIass die
(For
Hospital).
the
discovery
of
this
diem
from
Cooley’s
Moslems
1837,
Mediterranean
it
anemia,
who
nearly
70
live
yemors
in
was
U.
the
l)efore
countries
stated
to
occur
S. A.
Fermi
coined
t.hse
faba
minsor
(1837)
zauberhaften!
Hanre
die
(icr
schwarzens
Verfuhrerin
song
favistn
to
follows:
Vicia
Fort
about
Mediterranseans
and
sang
This
have
drmow
mir
unsd
ach!
I
am
einst
(C.
alle
schwer
S.)
Sinsnie
hcstrickt.
weissen!
gralefinl
mit
dens
to
Dr.
Tode
Panrl
gehuesst-!
Nat
hans
of the
Beilinssons
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A.
SZEINBERG,
C.
SHEBA,
I -Coin
TABLE
N.
position
of the
cninicam Diagnosis
1.
Test
HIILSHORN
Time
AND
Invest
after
ujalion
GOo
BO1)DNYI
EVA
Material
Country
Recovery
of Origin
cases
Hemolvsis
due
(Relatives
of mibove)
to
sulphms,
Hemolysis
due
to
drugs
6-24
monsths
10
Irmtq
6
PAS
Favism
6 months
1
Yemen
nsonths
10
Israel,
12-24
Yemsiens,
Irmiq,
Orient
ansd
Persimo
(Relatives
of
2. Control
above)
24
groups
Healthy
blood
dorsors
and
hospital
Ennrope,
Mediterranean
patients
2.
Relatives
3.
Control
with
no
of
the
group
history
above
person-is.
of Sephardic
Jews
of hemolytic
4. Control
The detailed
(healthy
blood
donsors
or hospital
patients
reactions).
group
of Ashkenazic
Jews
(selected
composition
of the various
groups
as above).
is summarized
in table
1.
METHODS
1
Fragility
.
studies:
Osmotic
troh)e,#{176}#{176}’
mechanical
Vicimi
was
fmsba
Minced
(pH
in
with
and
then
several
prepared
beans
shakers
and
filtered
were
invest igated
fava
salinse
refrigerator
and
by
greens
7.2)
frons
the
sheats)
for
migain
fluid
sera
ansd
mind test
mit. 4 C.,
room
temperature
ansd
37 C.
gation.
The
snnsceptibilit.y
to
hemolysis
saline
and
The
sera
(control
ervthrocytes
administration
2. Fetal
Singer
and
hemoglobin.
Chernoff.’2
Paper
Paper
(Stockholm)
2 hours.
by
constaining
the
case
which
Alkali
by
to
Isemolysis
The
The
to
The
the
5-20
Winby
sinffered
extracts
tested
by
slnlphmidiiazinse.
frons
hemolvtic
and
serum
resistmint
fetal
hsemoglobins
Wmis (lecminited
extract.
of
washed
insctnbate(h
slight
no similar
anerssia
(normal
the
arid
remodmifter
were
bnnffered
overnight
of
(hunted
mg.%
ins sahinse
fiini(I
Suspensionss
was
left
dilutions
cases.”
results
snmlphadrugs
of
was
sinpernsatminst
“test
nodded
ins 10 volinmes
suspenssions
Twofold
the
tested
of
in
0.1,
the
pH
Phosphate
buffer;
Acetate
Amino
acid
7.6;
at
was
8.0;
ionic
buffer:
5k51
buffers
7.25;
9.0;
cent
rifu-
method
ins
PAS
followinsg
mirsd owns)
solutions
of
strength
content
of
200V,
hemolysates
were
0.7
by
were
carried
milhiampere
ignited:
invest
est.insated
per
tsset hod
prel)ared
ourt
Barbiturate
tise
for
fetmol
Kellab
A.B.
for
5 hours.
The
lonsic
strenigt.is
0.05
by
miuer
with
strip
buffer;
as
of
a
9.8.
strensgt.h
ionsic
Blood
insvest-igatiomss
model
following
7.0;
hemoglobin.
electrophoresis
apparatus,
mobility
4.
obtained.
for
test)
electrophoresis
hemoglobin.
mind
hour.
were
and
similarly
onse
was
cases
described
snnsl)en(le(I
hour.
of
nssethod
Susceptibility
mis follows:
were
one
sera
the
PAS.
0.5-10%
3.
of
were
for
a clear
h’
Crosby.”
prepared
(including
normmol
test.e(1
of
mechanically
till
control
was
methods
ans extract
shmikers
times
ins salinse,
erythrocytes
fragility
fragility
0.1,
0.1,
pH
7.3;
1)H 4.0,
hemoglobin
7.5;
5.0,
8.0;
8.6;
9.18.
5.5.
h.ydrolysates
wmts
qumilitmitivelv
studied
chromatography.
Hemoglobin
exactly
120
C.
hydroxide
dilute
was
for
was
hemolysate
0.01
Gm.
12
hemoglohins
hours.
tnsinsg
Emoch
prepare(1
was
moliquot
was
phsenolphsthaleins
sulphuric
acid
centrifuged
and
was
filtered
as
added
as
added
just
through
to
for
fetal
10 cc.
of
nseumt rmohized
insdicator
to
the
glass
till
discoloration
wool.
The
hemoglobin.
8N
wit is Isot
thse
Ans
sulphsunric
snot urmoted
appearansce
point.
bmorium
aliqnnot.
acid
of
arid
comitmoinsinig
moutoclaved
sohunt ions
red
color
Sunbsequnenitly
stnlphat.e
precipitmote
of
at
hariunss
nOni(i t liens
the
material
was
well
From www.bloodjournal.org by guest on May 23, 2016. For personal use only.
606
ox
sTunmEs
wmoshsed
‘it Is hiot
lmn(ler
redunced
takens
Eti)
10%
ins a
concentrated
l)aPc
As
on
Two
hod
As
on
was
well
for
cvstine
from
(letections
reagenst
at
Glycolytie
2%
were
6.
were
the
before
our
the
dilnntion
differensces
the
in
2 control
extract
or the
was
The
drugs
and
found
As
identical
of
results
(aspart.ic,
for
glutamic,
lysinse,
chromatograms
were
acids,
the
namely,
iodotsset
it
by
the
sanssple
t yrosinse
Exanssiniationss
.
smonsiples
i)\
omnt ‘ithi
hydrogen
nsinihsydrinse
for
nseasure
counst
were
ai)ove
2%
method
hod
tsset
‘nishsed
in
as
wit
very
hemoglobin)
were
of
cmilculn.otcd
is
dilute
wmos made
exmtnflirse(I.
(iruersert
maid
mis nng.%
fragility
No
as
Pisilips,29
glutmothiotie
raised
((SH)
of
approximately
cases
detected.
acids
histidiuse,
and
test
hydrolysates
15 ansinso
methioniuse
detected
was
hensoglobin
of the
and
content
arginiine,
t.yrosinse,
the
of the Vicia
faba
of fetal
hensoglobins
hemoglohins
groups.
serine,
between
action
hemolyt-ic
contetst-
riot
(0.4%
over
nssechanical
constrol
cystine
ions
mind
ESTJLTS
proline,
were
t it rat
1)100(1
insactivated
rationi
the
by
nc
is quickly
No
glycine,
hensioglobinm5’5
identify
isel)muriniize(I
abnormal
amid
on
ansino
t hsc
useil
vhsere
,
ret-icumlocytes
t hie
counnst
shown.
acids
testleucine,
ins Isunsan
he
atninso
plsensylalanine,
Two
ionsal
Hollingsworthi21
with
concenst
demonstrated.
valimse,
tise
of
reagent..
cases
enzvnie
requnired
amid
could
the
to
by
by
ret iculocytes
osmsiot.ic
the
addit
wmos carriedh
fromis
the
no electrophoretically
analysis
out
\vas
(4 : I : 5 )
of tise
isatins
No
flseasilne(h
with
was
for
(1 vol.).
an
easy
descril)ed
separmited
to the
crises
the
cmorric(h
chloride
oxidation
an
employed.
alase
groups
sodiunm
after
with
1
No
smtmple
of solvensts
wit h molmirsinse,
out
7. Glulathione
(GSH)
has beerm estimated
modified
by Benntler
atsd assoc.9
Tise
results
in IIX) cc. l)acked
red cells.
and
her
used
was
grou)s.
blood
No
wmts
pmoir
mind was
method
was
examinsmition.
of
test.
hydrolysmutes
thse chronssatogrmtms
The
RB(’:
Cat
aniot
,
cc.
and
.
: micet ic mocid : ‘mtter
mocids
identified
Erythrocytes
for
tue
on
also
control
Allison.23
used
solutions,24
just
in
of 0.01
was
t nbc
.
activity
.1 etivity:
by
salinie
of
residtne
test
8 Hvdroxvquinsolinse.
her
cmirrie(I
aci(Is
was
glycolytic
(‘atalase
descril)e(i
ansinio
Activity
inscluded
also
molvbdmute
Prolinse
nsserst- of muerobic
toget
evnol)orate(1
Tbse
mu grmt(innntte(l
(leconspose(h
following
i ns h)unt ansol
were
of the
I 10 C.
the
The
0.1%
ot hser miminso
is
were
drynsess.
Ans aliqumot
ins 1%
with
ap)eare(l
t he
umm
of
filtrmotes
to
insto
hydroxide
unremu solution
dimensionally
ammoni
ophmunse
I Pau)er.
(1 vol.)
mmdl niethioninse
monsd
The
: 0.5%
mnlmost
volume.
bmtrium
No.
tyrosinse
one
separmtte(1
lx’roxide
t rvpt
chrommitography
: \Vater
svsteni
chrommttogra)he(l
ion
conshined
C.)
transferred
I cc.
exmtctlv
\Vhmotnsans
(4 vol.)
ins I his
to
Tise
(120
solutions,
l)rcParmit
(3 vol.)
Pisensol
agains.
bmith
wmos hydrolysed
paper
methsod
Isopropanol
.
5.
of
ion
dimensional
2.
mins(i filtered
baths
a water
solunt
noscens(hinsg
‘mtter
ins mu glycerine
isopropanol-water
clsromat.ographv.
by t his met
hsensoglobin
I
distilled
Pressunre
ERYTHROCYTES
idensitfied,
t hreonine,
trypt-ophane)
alansine,
auid
same
strength
fouisd
by
1)y ins amid were
gave
were
the
in both
various
spots
groups.
investigators
probably
lost
(lurinsg
preparation.
Glycolytic
activity
genital
spherocytosis
of
erythrocytes.m9’
the
disorders
cytes)
whether
sonic
sensitivity
The
1)een
of
results
also
high
are
in
of
in
our
presented
“test
showts
the
controls
amid
show
to
hemoglobin
activity
intrinsic
defect.
of carbohydrat.e
eryt-hrocytes
(unsproportional
glycolytic
that
ahtsormalit.ies
normal
younsg
in hoissogensous
ahtiornsality
IIBC
t.hat
activity
foutid
been
w’ith
St.udies
20
shown
Strikinsgly
have
It. has
is connected
have
activity.
of RBC.
the
cases
was
of
percentage
connsected
glycolytic
of
We
1 amid
ate
sumiussamized
with
ins t able
reticulo-
investigated
abnormal
cases.”
in figinre
1)100(1
various
inscreased
C disease.2m
ins eons-
nsetabolism
2.
From www.bloodjournal.org by guest on May 23, 2016. For personal use only.
A.
SZEIXIIEHG,
C.
Si-i EnIA,
N.
EItRSiIOitN
-‘
EVA
Ni)
(t)7
lUi)ONY
170160-
S
S
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S
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140-
4)
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.
S
S
S
k
130-
#{149}
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120-
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110-
S
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1555
.5
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nt ilized
ionit nols.
2.--
I cc.
t-ols
.
cc.
( tn-oimi)
lu;.
pen
1(X)
(
list
‘.
(‘atnilasi
of
(
Inst
‘.
H. B.(
.
(Rate
( roinp
of
Hl(
of
ti .
l{esinlts
‘.
( t-onmp A.
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Asisketinizir
2.--
Glqcolqtn’
Test
(‘.
No.
rols
(unit rols
cases
llisinlt
*
s nine (xi)ressc(l
as
tug.
,,
‘l’snun.:3.-
gI incose
iti 1izNI
(
.1
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V(l(i(it\’
nols
ghiniosi
Selillandic
(.n-ou
.
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is B. Stpiiardic
ni
(
111k
‘/
of (ait-
of
Rasige-
Ad
vi iv
\iea
is
20
21
17 86
It)
83
49
16
Il
72
46
ihinri tig
\shiketinizi.
con
I.
Sephiardic
cOtitr()ls
C.
‘fest
t rols
I burnt
hy
49
I (M) cc.
luacke(l
te(l
t
5
significant
gnonnp’’
( ‘u/u/use
anid
as
(xl)r(ss((l
are
(hilleneni(es
the
activity.
1/I1(
ii/
of (asts
Rangt-
2 tonst.nol
It has
tine nate of fornnatiomi
velo(i
t \ (oust
were
mitt
t
nssi
Mean
106
158
13(1
97
15(1
129
17
109
1(11
131
ti’
ins the
fonnnid
Activity’
of
14
12
(noses
Hesul
No
i’tii’iti,
No.
(roui
*
tug.
iti
( ;t’Oith) H.
((115.
1)100(1
-
tols.
Is
(unit
1(1/lit!/
-
(;rotij
(unit
(‘Xl)tPss((1
(i)t)t
cases.
inF:
A. Aslikenazic
B. Scphmtndic
glyeolvsis
Ashikeni:izic
.\.
2
(ases.
activity
( nis - intisoglohi
14.8
(iroimp
Fun.
i(’ act ivit y of
I(H( ‘ in I bout’
lvcolvt
(
.-
h’
I
) Pm
glyrolvt
I
((
(if 11
.
lutisogl
.
activity
I(
of
1)11
ti
I ha’
‘
ws
(li
t (st
grounps.
1 eeni
suggest
of nssethemoglobins
e(l
i)y
)ii(
len
ansd cholegioiumm
t limit
nat
a lasi
ins emvtlsnorvtes,
sl
ISV ii
svlih
From www.bloodjournal.org by guest on May 23, 2016. For personal use only.
tios
STUi)tES
siulfonsansides
accelerate
could
lead
ficiemst
cells.
and
\Vith
“test
this
cases”
ins table
their
t.o ant inicreased
Von-Protein
possibility
the
“test
Glutathione
I3eutler
atsd
which
necessary
for
cell
divisions,
irradiation
x-ray
assoc.
Isave
ansi line (lerivatives
glutathsionse
4.
tiouss
perforussed
The
orders,
fever,
results
the
ins
an
liver
impairnssents
the
of
to
Negroes
reactionis.95-27
patieusts
cases
with
in
(‘xanssitsa-
2-3
hensolytic
dis-
in the
control
included
were
low
3 and
figure
of
wit-h
other
some
associated
is
presenited
No
least.
insporcertain
and
ani average
present
psychotic
euszytnatic
are
nonprotein
against
primssaquine
findings
at
the
action
itsseveral
group
1 niousth
or
sumssnssarized
biological
protective
Ansericans
cases”
of
de-
constn’ol
activity
of
a widespt’ead
shows
Our
“test
interval
2 amid
consponenit
mssajor
sensitivity
of eryt.lsrocytes.9
at
mi figure
ins our
ins the catalase
has
amousg
cat-alase
groups.
participates
that
enscountered
constetit
table
and
showus
of the
(GSJi)
the
erythrocytes,
destructions
the
founid
control
comprises
the
and
examined
preseisted
the
of
ausd
poisons
are
were
compounds
is
we
1113(1
a(ti\’it-y of
catalase
amid
Co-rn pounds-Glntathione
(GSH),
tansce. It
results
cases”
low
Thus,
accumssulations
ins view
The
sSulfhydryl
sulfhydryl
formationi.
significant. differences
of
erythrocytes
EHYTHttOCYTES
choleglobins
groups.
3. No
OX
group.20
We
found
thsat all cases
T;L
i*
11o-
(
100
.
.
withs past
history
of favism
ot
hetisolytic
.
1.
t’ti/5/5.v
.;.
369
-
1-
1
O
?IM/o.’/
9
9
9
69
&0
So
SO
35
-j---.
779
.
6
C)
40
0
cc
#{243}#{231}
65
#{149}#{149}%.
I.
T
II
0.0...
...
6
90
105)
____
#{243}vo
00.
..
57
2.
oo..o
..
co
due
ausenssia
J
92
6
79
97
.
30
10.
rtni%1/LV
-6o7
10
9
-
Giow
(unit
3.-
rols.
(
1ltmt at bionic
Group
9
9
#{231}
6
6
-
-,0
-.1
43
46
Fun.
3
FnG.
Fn;.
0
55
(USH
( totit
B. Sephardic
emit of
controls.
( nusg./1(X)
1)100(1
Grump
C.
Test
cc.
cases.
4
ItBC
( Grotnp
Group
I).
A.
Ashsketiazic
Relatives
of
‘1
(st
cases.”
ho;.
lii utu
4.
(t
of favisnus.
-II l3(
‘
glint at-bionic
100 (c.
3
:orsd hsemolvsis
past
RBC
( . (II
history
chine to
(GSII
past
(
(Oti((tlt
hsist ory
of hensolysis
sulphsap-ridinse
rat
ioni
of iietssolvsis
it)
3
fami lies
(line
dune to miniunsknsowni
( figtit(’s
to smnliuls:o
drung.
ilrsngs
(4) past
tdI)t(setl
.
(2 ( Past
history
t
gI sit a
iiist
ut-v
of favismss
From www.bloodjournal.org by guest on May 23, 2016. For personal use only.
A.
SZEINBERG,
C.
SHEBA,
N.
4.-Glutathione
TABLE
HIRSHORN
(GSH)
AND
Content
of
EVA
Ergthrocyles
Ashkenazic
B.
Sephardic
C.
Test
constrols
111
controls
111
cases
The
*
-
21
results
mire
Mean
Range’
Group
A.
cmilculat-ed
as
(GSH)
glintathionse
(109
BODONYI
Stand.
Deviat.
47-111
77
13.5
32-ho
77
15.2
35-56
47
6.5
concentrmotion
per
100 cc.
(mg
%
A
case
packed
erythrocytes.
5-Blood
TABLE
(1)
A case
hsistory
of
of Glutathione
(GSH)
per 100 cc. RBC)
Concentrations
with
Past
history
of
hemolysis
due
in
7 Families,
t.o sulpha
dnngs.
(2)
3
4
Family
5
Family
6
6’
9
52
37
d’39
(1)
63
47
(1)
2
?
41
49
7
8
40
Family
9
34
were distinguished
Statistical
auialysis
to sulpha drugs or PAS
its their
red blood
cells.
difference
signuificant.,
differetuce
incidence
its the
Sephardic
constrol
Whet-her
this
Glutathiomse
D),
fig.
a real
convey
(11 %)
(Ins family
subjected
the
our
(2)
d’4()
(2)
942
(2)
c4l
(I)
than
(2)
o”4()
1
of glutathionie
proved
that
the
groups
is highly
the two coustrol
groups
as a
(below
60 nsg. %) was higher
the
in
940
one
Ashkenazic
will have
group
(5%).
to he ascert.ainsed
by
estimated
in the
test
The results are presented in figure 3
its this group
show a very high inscidenice
5. The
Out
cases.
results
of 48 persons
60 mg/100
anomaly
cc.
ansd not
with
insspression
of the presence
but
the material
is still too
occurreusce,
found
table
below
fansilial
ati
of
values.
concetitration
ivith
also
was
childrets)
4* atsd
glutathione
low
thione
on
(GSH)
ansd
(group
*
957,
o50
t.hse 2 cotitrol
bet-weets
values
(1)
(1)
Studies
(parents
was
and
has beens founsd
of low glutat-hionse
group
935
42
by a low cotscentration
by the “t” test has
is a casual
finding
or a significanst
of much
larger
groups.
examination
of
?
between
the group
of “test- cases”
(P being
smaller
thani 0.001).
significanst
hut the
Generation
d’47
?
Family
Family
?
49
Family
No
whole,
past
Generation
Second
Family
wit-h
favism.
First
Family
Glutathionc
No
10 rio hemolytic
to
have
to
insvestignotions.
problem
1)100(1
of
familial
The
of 53 mg./100
findings
incidensce
ins this
of
of a small
glutathionse
group
of relatives
studied,
38 (about 80%)
RBC.
This suggests
tisat we
a casual
finsding.
The figures
of a recessive
gene
small
for a thorough
occurrences
glutathionse
blood
Isave
beers
cc.
family
knsown;
1tBC
ansd
are
repOrte(1
deficient
dealing
preseusted
responsible
for this
genetic
evaluation.
a girl
her
had glutaare
in the
whsole
here
eryt.hrocyt.es.)
control
fansily
as
they
gronmp
has
1)enor
been
also
From www.bloodjournal.org by guest on May 23, 2016. For personal use only.
(110
STUDIES
TA ninE
6
ON
Changes
.-
Case
in
ERYTHROCYTES
Blood
Lnsgestion
of
i___
Reticulo-
mg.,’toocc.
Date
Hernato-
cytes
(i_______R1______
beatss
-
mg/moo
cc.
RBC
#{182}15
I
-
10.4
Symptoms
notes
11.4
11.4
-
exam.
-
12.4
19
13.4
20
14.4
20
15.4
20
17.4
23
6.5
39
20.5
38
29.5
39
14.6
33
7.8
34
81
63
12.4
15
13.4
18
65
14.4
21
130
65
15.4
23
120
61
17.4
24
!
-
Glutathione
Sonsse
(GSH)
of our
of
Content
cases
were
linuits,
and
the glutathioise
(GSHt
tsug/100
cc. RBC).
Two
These
rensained
finsdings
nuniubers
such
could
after
of this
problenss
18.4
27
28
75
3
67
20.4
28
68
12
55
22.4
29
17
42
23.4
30
8.5
42
30
67
6.8
44
11
40
During
by
the
us also
Acute
Stage
duritsg
the
crisis
appears
subject
85
90
72
81
(if Hemolysis
acute
About
stage
three
dropped
of such eases
by a isypothesis,
henuolytic
175
of
favisnu
IthC
glut.athionse
content.
it. was foutsd to l)e within
(1-8 weeks.
concentration
exanuples
is the
78
71
-
19.4
at- least
a defect
86
160
63
h)e explainsed
the
hut ins old erythrocytes
or decreased
synthesis.
Study
for
67
69
amid have
shown
ititereostinig
changes
in their
studied
a few days after
thie onset
of the disease
attack
(35-45
53
220
7
N.B.C.
studied
280
-
23
-
I
great
2
Gnutath.
I
cytes
.
10.4
Blood
Favism
Case
Hernato
------
-------
1 cute
t
ReticuloDate
Following
are
leading
that
young
to
to its increased
after
the
low values
ins table
6.
cells
in regard
either
of further
nuuonths
to deflisitely
are presemited
nsormal
When
nornual
formned
in
glut athione,
destructions
investigation.
DiscussIoN
The
prevalent
concept
sensitization.30probably
3ta.
tOt)
ion
Dacie
of
the
pat-hogensesis
classifies this
of
favism
conditions
as
is
that.
“heniolvtic
of
allergic
ansensia,
of allergic origins.”
This consception
attack by ingestion
is h)ased ons a possibility of precipitating anu acute Isensolytic
of a very sniall amount
of fava beans
(even onse beans is some-
times sufficient) or by inhalation of its pollens, short
incubation
period
amid positive skin test-s
as reported by several authors. A serologic mechanism
unsderlying
this disturbance
is suggested
by a positive
Coonubs
test
and the presence
of
henuolysins
reported
by sonic insvestigators.32
A sinuilar
explanation
is suggested
for
acute
hemolysis
occtnrring
TIse finsdings reported
erythrocytes,
namely
durinsg
suipha-drugs
insthis paper
glutathionse
therapy.
suggest- that
deficienscy
a
0e
const-itutionsal
is esseistial
for
the
5th
anomaly
of
pathogensesis
of
From www.bloodjournal.org by guest on May 23, 2016. For personal use only.
_t.
these
conl(hit.iomn).
that
the
were
returne(l
feature
of
ins these
a bug
\Ve
It- seems
low
that
after
assume
show
amid test
it is highsly
exists
prior
when
that
are
that-
glutathsionse
to it. All the eases
t.hse henssat.ologic
deficiency
ins view
of the
conscenitrations
only.
the
this
to be hereditary
insuprobable
clsans(e
certain
recovery,
therefore
glutathionse
that.
61 1
BDDONVL
EV.-
groups
it seenns
but
timsse
can
cases.
ssithi
persons
point-,
.tXD
dat-a
control
of hensolysis,
exaissunied
to nsornsal.
HIRSI-IORN
of the
the
at- this
is niot. a result
us
N.
anialysis
i)etsveens
be stressed
(leficienl(y
SHEBA,
Statistical
(hflerelsces
It should
by
C.
SZEIXIIELIG,
ansiong
the
stu(iied
stat-us
is a permusarsent
high proport-ioni
relatives
of
aflected
eases.
A sirssilarity
ins the
at
present
tietsts,
Tise
tise
there
to
be
8 which
:3-S days
aft-er
rapid
is usually
as
to
When
and
all
of
losv glintathionue
beanss
52
nssg. -‘100 cc.
RBC
nssaterial
the
reactions
sulpba
bitt
whets
a few
weeks
of
the
to
it
are
similar
to
prinsaquinse
induced
insit.ial sharp
primaquinse
drop ins the
adnsiiniistrat.ioni.
already
period.
ins the hensolyt-ic
(The in vitro
test.
Auothser
tat
hionie
problenu
with
did
cells
of
GSH
eaten
not.
of
prinsuaquimse
phosphate
oxidized
glutat.hionse.
We studied
the
oxidized
group
find
ansd
did
niot
also deficient
ins oxidized
defect
in tIll’ nssechatsisnis
insvestigat ion.
direct
amid
glutathsione
for
glutathione
reducing
assoc.33
did
develop
prehemnolytic
by us reached
oxidation
of
This
also
constent
values.
the
its the
On
as well.36
glut-athionue
the
These
exists
thsinsk
aisd
fol-
period
the
during
hospital
to study
the precedinsg
yet. beens exploited
by its.)
causing
the
ins a recent
ins the
glucose
abniornusality
possil)ly
\Ve
in cases
of
nsot flnsd the
We
is the nsechansism
et al. demsionist rated
subjects.35
inicreased
amid
except-ions.
its the
studied
elucidations
es. Carsonn
activity
atsy
Flansagans
had nio opportunity
by Beintler34
has not
ins the
seussitive
dehydrogensase
we
fava
value
againi
omue insportaust
level occurrinsg
As all the patients
stage,
described
ann ahnornsnalit-y
by
low
persons
a glut-athionse
and
ansd
took the drug,
a hensiolytic
that favism or hemolysis dine to
consditionss
are fulfilled:
(I) glim-
later
described
with
which
awaits
erythsnocyt
defi(icnicy
munuicat.ions
those
anenssia,
the
period
musaterial
to have
with
sulphadiazine
and
8 persons
clainsed
hospital
drug
be so severe
Ins our
group”)
hemolysis
inicunbations
destruction
nnay
death
occurred).
ins our
formsiat.ions
studies
The
primaquine
“relatives
the
tathione
deficiency
of enythrocytes,
(2) sensitizations
to noxious
agenit-.
t.hat our knowledge
is still too fragnssenstary
to decide
oni this.
The
chansges
ins glutat.hionse
level durinsg
the acute
stage
of favisns
lowinsg
pa-
of
favism.
ceuit-.
hennolysis.9
administered
was
per
she
followed.
A theory
could
be proposed
drugs
appear
only
si-hens 2 sinsultaneous
heniolysis,
coniclunded
groups
witis
in
In controlled
48
no
developed
A patient
harnss.
be
ins both
adnuussistration
to
adnssinuistered
thenus
(ansuong
evident
without
22
amid thse blood
associates
glutathsiouse,
found
limited.
of
fronss
our
(iii
deficiency
not
is associated
nsot- beets
heginisimig
short
deathiob
glutathionie
it should
is identical
disease
is self
rmsnsged
very
cause
Beuntler
blood
the
fall
ansd the
Still,
of differensce.
have
anemia
hensoglobirs
of fa.visnis
point-s
hemolytic
bodies,5
here
is evident.
(sf hensolysis
sonic
prinsaquine-caused
niaxirusal
presensted
Negroes
nsechansisnis
seens
Heinsz
appeared
aniy
findings
prima(luine-caused
The
with
the
senssitive
that
as
of many
of
betweeii
primusaquinse
for
erythrocytes
constrary,
result-s
ins the
reducinsg
of
nuost.
suggest
subjects
-
red blood
glucose
6
affects
nssechansisnss
glucotss
our
cases
that
mnnsder
test
were
no
our
From www.bloodjournal.org by guest on May 23, 2016. For personal use only.
012
STUDIES
OX
EtIYTHROCYTES
S unI;
Studies
acute
have
been
due
hemolysis
No
insdicat.ion
carn-ied
out- on en’ythrocytes
to Favisnin,
suipha
drugs
was
foutsd
of abnuornuual
mobility
of hennoglobins
glycolytic
or catalase
activities
trophoretic
nsa!
relatives
No such
major
so far
studied,
t.o the
same
ethnographic
Tisis
both
aided
was
Studios
del
erythrocytos
causate
trovate
nsobilitate
ha
nnenste
niulle
de
activitate
de glutathionsa
Carenitias
st-udiate
e esseva
Nulle
tal
essite
uts
carenitia
discovered
a frequent
was
was
from
in the
the
executate
dee-
no
ahusor-
ins all cases
finding
among
cases
any
of thalassemia
exceptions
Israel
Research
belonsg
Counscil.
in casos
o constent.o
de
o cat-alase
esseva
in le eryt-hrocytos
historias
esser
acut.e
o nuechansic,
Simile-
detegit-e.
ins omne
le casos
del pat.ienstes.
muter
poteva
de
amino-acido.
esseva
discoperite
le cotssanguiiseos
frequenste
de glutathionsa
con
sulfa,
o acido
para-aminosahicylic.
anornsal
fragilitate
osmotic
de glycolyse
consstatationu
fragility,
Similarly
svithout
hetnoglobinsa,
ansormal
of
IN INTERLINGuA
per favismo,
drogas
nulle
indications
de
electrophoretic
history
(nsons-Ashkensazic).
a granst
SUMMARIO
hemolyse
Esseva
conteust.
be estab)hshed
ions
by
past
detected.
patient.-groups
denonuunsat
with
or mechanical
acid
eryt-hrocyt.es
deficietscy
coul(1
though
insvest-igation
osmotic
were
of affect-ed
cases.
glutathione
deficiency
of cases
PAS.
or
or it-s aminso
Glutathione
(GSH)
deficienscy
of
studied.
Similarly,
glutathiotie
(GSH)
the
nov
in le casos de t-halas-
establite
semia major usque nunse studiate,
l)ens que amhe
gruppos
de patieistes
representtava sinsexceptions he mesnue divisions ethnographic
(i.e.judeos usons-ashkenazim).
1st-c
insvestigation
sul)vetstionsat-e
esseva
per
Ic Conisilio
de Recercas
tie Israel.
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To
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From www.bloodjournal.org by guest on May 23, 2016. For personal use only.
1957 12: 603-613
Studies on Erythrocytes in Cases with Past History of Favism and
Drug-Induced Acute Hemolytic Anemia
A. SZEINBERG, C. SHEBA, NINA HIRSHORN and EVA BODONYI
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