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Oxymetholone
Treatment
By Raymond
for Sickle
Alexanian
and
Seven
patients
with
sickle
cell anemia
were
treated
with
oxymetholone
for at
least 2 mo. Markedly
increased
basal rates
of hemolysis
and erythropoiesis
were confirmed.
The urinary
erythropoietin
excretion was either normal
or lower
than expected
for
the red cell mass,
and
an
expanded
blood
volume
was
due
primarily
to an increased
plasma
volume.
After
androgen
therapy,
six
patients
demonstrated
more
than
a fivefold
increase in urinary
erythropoietin,
with
an
increase
in red cell mass
ranging
from
D
MORBIDITY
ISEASE
results
from
infarctions.
to markedly
useful
In addition,
increased
in some
“crises,”
Nadell
patients
or
with
from
the
sickle
end
with
anemia
due
to bone
cell
results
some patients
are symptomatic
rates
of red cell destruction.
patients
Anemia
1 7%-75%
above
the central
value.
All
showed
a decline
in serum
iron level to
the 25-75
ug/100
ml range within
4 wk
after
the start of therapy.
Less marked
changes
followed
lower
oxymetholone
doses. Reversible
hepatic
toxicity,
with a
serum
bilirubin
concentration
exceeding
50 mg/100
ml, occurred
in one patient.
Androgenic
hormone
therapy
may be useful for selected
adult
patients
with sickle
cell disease
when
severe anemia
contributes to disease morbidity.
in most
painful
Judith
Cell
anemia
of
attention
to this
marrow
failure,Ia
of therapy.7
in patients
with
Patient
MATERIALS
AND
basal
rates
of
of
the
erythropoiesis
were
increased.
METHODS
Characteristics
Seven patients
with
though
androgen
cell
mass
even
oral
sickle
red
patients,
an
clinical
benein some
pahave
devoted
alkylated
class.
This
report
summarizes
an evaluation
of erythroand of oxymetholone
treatment
trials
in seven
patients
with sickle
cell
Results
indicate
marked
elevations
in erythropoietin
excretion
and in
in most
oxymetholone,
recent
have
markedly
with
studies
and
17-alpha
kinetics
anemia.
cell
conducted
No
due
are
disease
already
been
mode
organ
from severe
anemia
Androgenic
hormones
studies
have defined
erythrokinetic
criteria
from
which
to predict
fit in individual
patients.3’4
Androgens
have
been
reported
useful
tients
with sickle
cell anemia,5’6
but recent
reviews
on treatment
little
usually
multiple
with
oxymetholone.
sickle
Their
cell anemia
ages
ranged
had erythrokinetic
from
14 to 48;
studies
five
were
before
male;
all
and
were
during
black.
treatment
Pain
crises
were infrequent
in all, averaging
less than two per year during
the preceding
3 yr. All
were
symptomatic
from anemia by virtue of easy fatigability
and/or
dyspnea on exertion.
Anemia was
severe
in
exceeded
all,
From
the
Institute,
Address
University
Blood,
ml,
Department
hematocrit
and
ranging
the
fetal
of Medicine.
ed June18.
Supported
©
the
from
20-26
hemoglobin
The
vol/l00
ml
concentration
University
of Texas
(Table
was
M.D.
less
I).
The
Anderson
serum
iron
l0#{176}/
in all.
than
Hospital
and
The
Tumor
Houston.
Submit:
Texas
with
65 .ig/l00
1974;
by USPHS
for
of
reprint
Texas
accept
Grant
requests:
M.D.
AM
ed January
Raymond
Anderson
23. 1975.
09/55.
Hospital
A lexanian.
and
M.D.:
Tumor
Associate
Institute.
Professor
6723
Bertner
of
Medicine,
A venue.
The
Houston,
77025.
1975
by Grune
& Stratton.
Vol. 45, No. 6 (June), 1975
inc.
769
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
AND
770ALEXANIAN
0
E
0000000
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00
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C’)
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ED
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NADELL
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
OXYMETHOLONE
reticulocyte
ranged
All
TREATMENT
concentration
from
6.3 to
patients
were
red cell
red
cell
or
In
all
scanning
and
red
A ndrogen
from
patients,
the
rate
of
evidence
at least
half-time
Squibb
30
4 wk
for
&
for
the
ml/min
prior
hematocrit
in
all
to any
patients.
studies.
Inc.)
results
and
expressed
the
red
cell
labelled
x
as
normal,
blood
red
volume
The
ranged
from
cells
with
was
12
1251-labeled
derived
erythropoietin
as Standard
4
mass
simultaneously
total
iron
calculated
in the extremities.’0
The
of 51Cr
urinary
Plasma
was
exceeded
expansion
51Cr.1’
measured
The
turnover.
turnover
production
disappearance
volumes.
iron
iron
marrow
was
Sons,
erythron
cell
with
volume
plasma
with
red
measured
plasma
and
the
erythron
of bone
were
the
E. R.
defined
the
and
previously,
Oxymetholone
was
and
by 50%
iron
51Cr
administered
160 mg/sq
of
to the women
with
for
corrected
than
from
excretion
was
the
mea-
B units/day.’2”3
Treatment
2 females
serum
index
greater
I mg/day
and
survival
red cell
as described
creased
acid
was
59Fe
1). The
(Albumotope,
of the measured
sured
reticulocyte
with
showed
cell
less in all (Table
albumin,
the
clearance
was
conducted
40#{176}/,-60% of normal
days
and
folic
production
were
body
mass
about
12%,
creatinine
on oral
previously.4’9
and linear
sum
of
studies
described
The
771
Studies
rate
turnover
SICKLING
exceeded
1 1.0.8
maintained
Erythrokinetic
The
FOR
at monthly
was 63 mg/day,
at least
for
and
were
patients
five
intervals
concentration
after
to all
m to the
in an
males.
a minimum
to the men
monitored
268
daily
absence
9-wk
dose
of side
treatment
mg/day.
at monthly
2 mo of androgen
initial
In the
period.
Hematocrit,
intervals.
of
The
red
40
mg/sq
affects,
the
The
m
dose
mean
liver
function
cell
mass
was
to
the
was
in-
daily
dose
studies,
and
remeasured
therapy.
RESULTS
The
red
cell
the seven
5 vol/100
mass
increased
treated
patients
ml. The only
toxicity
after
2 mo,
from
17%-75%
in association
exception
was
with
no change
elevation
in red cell mass
third of the red cell mass
in red
for all was 190
in these patients
man (normal
range
900-1250
ml/M2).
in all five patients
with measurements
(Fig.
1). The
from
0.75
ratio
to 0.85,
of the
and
body
also
markedly
to levels ranging
with
a decline
of at least
Serum
lone
iron
was
values
did
hematocrit
not
the
for
the
the survival
lone,
when
following
*Written
level
in six
increment
who
developed
or hematocrit.
of
of at least
hepatic
The
median
represents
about
oneof the mass
in normal
volume
remained
unchanged
after
at least 2 mo of therapy
the
venous
Serum
control
control
m, which
about
20%
to
change.
to the
disappearance
and immediately
study,
5’Cr-tagged
oxymetholone
evidence
mass
from 25 to 75 ig/l00
25 zg/100
ml within
recovered
the
iron
hematocrit
ml after
one
4 wk in all
range
ranged
concentration
within
declined
mo of treatment,
patients
(Fig.
2 wk
after
1).
oxymetho-
terminated.
slope
during
In this
cell
mi/sq
and
The plasma
before
and
No change in red cell survival
was
treatment
in two patients
with detailed
lar
above
with a hematocrit
patient
A.C.,
trial
studies
were
the hematocrit
of a shortened
the
cessation
informed
consent
of
following
red cells
when
the
noted
during
the period
of oxymetholone
studies.
Figure
2 demonstrates
the simi51Cr-tagged
hematocrit
continued
had
until
declined
red
survival
cell
red
the termination
were injected
had
from
in one
increased
from
14 days after termination
to 24%.
As indicated
was
of therapy.
was obtained
cells
of oxymetholone
10 days
before
all patients.
found
during
patient
(R.T.)
treatment.
completion
25%
to
of oxymethoin Fig.
2,
the
control
of
31%;
period
no
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
AND
ALEXANIAN
772
NADELL
000
C’J
E
a
500
0
C-)
0
E
3000
o ct
>
o
-
2000
0.
250
200
Fig.
50
iron
00
U)
50
0
4
Duration
Urinary
treatment.
of
12
(Weeks)
erythropoietin
excretion
was
Figure
3 compares
pretreatment
therapy.
Basal
erythropoietin
dicted
for the red cell mass,
than 5 x the value
predicted
Since the red cell
4 wk of androgen
time
6
8
Oxymetholone
of the
urinary
mass
were
excretion
was either
but the posttreatment
for the new red cell
erythropoietin
enhancement
of erythropoietin
dose of oxymetholone
(Fig. 3).
After
an interval
of at least
daily
oxymetholone
decline
in serum
100 ml range),
increase
after
patient
collection.
excretion
four
from
was
in urinary
red
and
during
cell
serum
oxy-
and during
results
after
androgen
1 mo
of
normal
or lower
than
preexcretion
increased
by more
mass
in all but one patient.
1 mo of treatment,
values
after
from
the curves
in Fig. I at the
women
1 mo,
patients
showed
despite
were
their
retreated
25%-40%
of their
less marked
(i.e.,
erythropoietin
0
in
volume
concentration
before
with
Both
after
4 wk,
doses
ranging
iron
concentration
the
measured
values
was not measured
derived
for each
Changes
metholone
treatment.
Substantial
elevations
in red cell mass wore
associated
with
no change
in
plasma
volume
and with serum
iron values declining within 4 wk
to the 25-75
pg/100
ml range.
The shad.d area includes the range
for all serum iron values after the
first 2 wk of treatment.
0
E
1.
plasma
mass,
was
less
initial
to the
(i.e.,
a marked
lower
daily
with
mean
dose.
55-90
two
The
.tg/
of three
400
300
.
200
Fig.
2.
The rate of disappearance
t1Cr-Iabol.d
red cells in a patient
sickle cell anemia
during
the final
10
of an oxymetholone
treatment
trial
th. hematocrit
was 31%,
and for 14
after oxymetholone
was terminated
the hematocrit fell to 24%.
of
with
days
;:
Treatment
when
days
when
0
c
5
I0
Time (Days)
‘5
20
25
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TREATMENT
OXYMETHOLONE
FOR
SICKLING
773
0
Fig. 3.
Effoct of oxymetholone
treatmont on urinary
.rythropoi.tin
excretion in patients
with sickle cell anemia.
Solid circles
indicate
basal
values and
open
circles the urinary
erythropoietin
after
1 mo of oxymetholone
therapy.
The shaded area indicates
the range
for the relation
between
erythropoietin
andredcellmassin90%
of 36 pa-
tients with varying degrees
due to bone marrow failure.
with
evaluable
elevation
parison
studies
Most
patients
toxicity.
In
creased
a slight
/
to
5
i
200
400
600
800
0
200
400
did
not
(i.e.,
results
tolerated
achieve
a fivefold
oxymetholone
male
patients
increased
patient
(A.C.)
stimulation),
and
there
receiving
the
low
was
reaching
less than
650 ml/sq
m in all),
after their initial
treatment
trial.
with
receiving
virilization,
with
Within
6 wk after
the
returned
to the pretreatment
patients
600
800
Red Cell Moss (muM2)
a low
high
marked
frequency
doses
and one
and
termination
range.
jaundice,
No
oxymetholone
less
in comdegree
of
had muscle
aching,
one
male
developed
hepatic
the
total
bilirubin
from 5.5 mg/i#{174} ml to 52 mg/i#{174} ml after 2 mo of treatment
elevation
in liver
enzyme
values
and
no change
in serum
phosphatase.
level had
the
this
‘
of anemia
in red cell mass
with the superior
side affects.
Two
woman
demonstrated
2
in-
with only
alkaline
of oxymetholone,
the bilirubin
side affects
occurred
in any of
doses.
No
apparent
change
oc-
curred
in the frequency
of “pain
crises.”
The blood
volume
was evaluated
in all seven
patients
treated
with oxymetholone, as well as three additional
untreated
patients.
Basal
values
for total
blood
volume
were above
the upper
limit of the normal
range
in all but one (Fig.
4);
the plasma
volume
was also higher
than
predicted
for the hematocrit
in the
same patients
with an increased
blood
volume.
The expanded
plasma
volume
accounted
completely
for the measured
increase
in blood
volume.
The
mea-
40
//
\#{174}.,,.
#{174},
..
20
0’
‘
2000
,,
I
3000
Blood Volume
(muM2)
000
2000
Plasma
Volume (mI/M2)
3000
_________
500
000
Red Cell Mass (mI/M2)
FIg. 4.
Basal values for blood volume, plasma volume and red cell mass in patients
with
sickle
cell anemia. The solid circles indicate measurements
in comparison
with the ranges for 46 measurements in 34 patients with anemia due to marrow failure. No patients with splenomegaly
or
serum monoclonal gammopathy
were included in the control ranges. The circled values represent
patients with blood volume studies who did not receive androgen treatment;
in one of these patients, only the red cell mass was measured.
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
774
ALEXANIAN
sured
tients
red cell mass was greater
than
predicted
for
(Fig.
4). There
was no significant
correlation
the expansion
excretion
was
of total
depressed
blood
below
volume
and the
the level predicted
the hematocrit
between
the
AND
NADELL
in most
magnitude
degree
to which
for the red cell
paof
erythropoietin
mass.
DISCUSSION
This
of the
study
evaluated
17-alpha
alkylated
evidence
production.
and
of
were
excretion
tion.
have
provided
was
and markedly
increased
an adequate
iron supply,
supplemental
serially
folic
as an index
demonstrated
basal
or depressed
for the
to the
red
for
the
acid.
cell
mass
levels
The
increased
blood
compensated
in comparison
flow,
tion,
cells
in sickle
cell
the
with
anatomic
are
erythropoietin
produc-
as infection,
that
might
that
were
either
Erythropoietin
values
sickle
cell
expansion
more
effectively
with
other
anemia
urinary
erythropoietin
patients
and
levels
of red cell
renal
function,
in erythropoietin
of anemia.
in some
may have
for oxygen
red
of
an oral
androgen
anemia.
All showed
basal
adequate
of changes
degree
marrow,
that
requirements
the
of oxymetholone,
with sickle
cell
complicating
factors
were present,
such
maximal
levels of bone marrow
activity.
predicted
be due
with
assessed
patients
appropriate
than
clinical
utility
class,
in patients
severe
hemolysis
All patients
had
No overt
impaired
All
the
for
anemic
considered
may
of the
bone
the increased
states.’4”5
to
have
less
anemia
tissue
In addi-
a low
oxygen
affinity
with a shift of the oxygen
dissociation
curve
to the right.’6”7
The improved
oxygen
delivery
from this adjustment
may further
inhibit
the need for a
maximal
increase
in erythropoietin
and red cell production.’8
Finally,
this report confirms
a markedly
increased
total
blood
volume
in most
adults
with
sickle
cell
anemia.
The
total
blood
found
in other
patients
with
primarily
to marked
elevations
creased
plasma
with a decreased
to the
have
volume
body
conclusions
an
expansion
other
All
lowing
hemolytic
patients
at least
reached
for
of total
blood
degree,
This
children,’9
and
conclusion
about
adults
that
Erlandson
cell anemia
50%
greater
marrow
failure
The mechanism
but this
hematocrit
most
volume
may
change
was
ratio.
Thus,
with
sickle
contribute
also reported
in comparison
is capable
that
was due
for the inassociated
in contrast
cell
anemia
substantially
an increased
with children
significant
treatment.
to
plasma
anemic
elevations
in red cell mass
folThe frequency
and magnitude
were
similar
to the experiences
of others
increased
red cell mass
in all studies
was
was
attributed
was
supported
to a further
by our
stimulation
failure
to detect
of
any
using
usually
red
of producing
red
cells
at more
than
this
parenteral
of moder-
cell
production.
changes
in red
survival
in two patients
and the marked
decline
in serum
iron
during
the oxymetholone
treatment
period.
Lundh
also failed
to
producible
alteration
in red cell survival
in three
patients.5
The
red cell production
in our patients
was about
six times
normal,
to that
reported
by others.9’2#{176} Finch
has demonstrated
that
the
marrow
than
and
anemias.2#{176}
but one demonstrated
2 mo of oxymetholone
of this stimulation
testosterone.3’6
The
ate
was
to bone
volume.
was not determined,
hematocrit/venous
an increased
oxygen
transport.
volume
in children
with sickle
from
volume
anemia
due
in plasma
level,
cell
concentration
detect
any remedian
rate of
a level similar
human
bone
provided
ade-
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TREATMENT
OXYMETHOLONE
quate
iron supplies
marrow
stimulation
FOR
SICKLING
775
are maintained.9
These
findings
confirm
will occur
in most
patients
with sickle
their high basal
rate of erythropoiesis.
found
with lower oxymetholone
doses,
between
androgen
dose
tion.
Consistent
within
several
reductions
wk after
to that
in some
found
cancer,2’
red cell
the
magnitude
of the
with
bone
changes
in the hemolytic
rate,
to an increased
magnitude
subjects
with
may
stimulated
effect
iron
increase
in serum
iron concentration
the start of androgen
treatment.
patients
marrow
failure,4
cell
in women
produc-
with
who
developed
In the absence
A less
in a manner
in red
were noted
in all patients
This decline
was similar
such
reductions
of iron turnover
erythropoiesis.
metabolism
bone
despite
Less stimulation
of erythropoiesis
was
suggesting
a dose-response
relationship
and in elderly
men with
osteoporosis,
production
during
androgen
treatment.
mented
attributed
gens
and
that
further
cell anemia
breast
an increased
of any docu-
in serum
iron level were
to the bone
marrow
in
likely
possibility
unrelated
is that
andro-
to erythropoiesis.
No changes
in plasma
volume
were
detected
in five patients
after
at
2 mo ofoxymetholone
therapy.
Boada
and Frumin
reported
an unchanging
increased
plasma
volume
in four patients
with
sickle
cell anemia
treated
nandrolone.6
Lundh
and
patients
with sickle
tions
may
account
Lundh
and
hematocrit
our study.
1 1 patients
treatment;
period
present
Gardner
calculated
cell anemia
who
for the varying
Gardner
and the
estimated
red cell
a decrease
also received
conclusions
plasma
mass
in
volume
contrast
in plasma
nandrolone.5
concerning
our study.
Finally,
of the different
gests
with
during
urinary
patients.
failure
that
sickle
from
the
measurements
major
androgens
studies.
Of interest
is that Gardner
had previously
reported
volume
of more
than
25% in 4 of 15 elderly
males
with
with
nandrolone,
emphasizing
the difficulty
in interpreting
The
of our
marrow
in
explanavolume.
venous
in
Secondly,
the treatment
period
was 8 wk or less in all but 2 of the
treated
by Lundh,
while all of our patients
received
at least 9 wk of
thus, transient
declines
in plasma
volume
during
the early
treatment
may have
been
missed
in
in the nature
and schedule
hematocrit
volume
Several
plasma
in their patients
to the direct
least
or
with
the early
treatment
elevations
osteoporosis
slight
were
these
in plasma
treated
changes
in
period.22
erythropoietin
excretion
Similar
elevations
have
who received
identical
the increased
cell anemia
differences
used
in
erythropoiesis
resulted
from
increased
at least fivefold
in all but one
been documented
in patients
with bone
oxymetholone
doses.4
This
finding
suginduced
a stimulation
in
androgen-treated
of erythropoietin
patients
produc-
tion. Gordon
has demonstrated
that androgens
enhance
erythropoiesis
in animals
by increasing
the production
of a renal
erythropoietic
factor
(REF).23
Whether
oxymetholone
also stimulated
the bone
marrow
of these
patients
by
other
mechanisms
study.
Levere
erythroblasts.24
independent
has
provided
Androgens
by triggering
more
to erythropoietin.25
plutipotential
Gorshein
of
evidence
may
for a direct
result
and
erythropoietin
in more
cells from
Gardner
was
not
action
cells
a G0 phase
concluded
evaluated
of certain
sensitive
to
in
androgens
this
on
erythropoietin
to a G, phase
responsive
that
19-nortestosterone
decanoate
stimulates
a larger
number
of erythropoietin-sensitive
protect
the bone marrow
from the affects
of Actinomycin
cells that may
D.26 Thus,
increasing
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
776
ALEXANIAN
evidence
supports
stimulation
liferation
a dual
role
oferythropoietin
of primordial
for
androgens
on
erythropoiesis,
production
and the second
sensitive
to erythropoietin.
cells
AND
the
from
first
NADELL
from
an increased
a
pro-
All but one of the patients
tolerated
their
androgen
treatment
without
major
side affects.
In the one patient
who
developed
hepatic
toxicity,
the marked
hemolytic
anemia
undoubtedly
contributed
to the magnitude
of the hyperbilirubinemia
(i.e.,
to more
than
50 mg/l00
ml).
Although
a larger
number
of red
blood
cells susceptible
to sickling
was produced
in most
patients,
there
was no
increase
in the frequency
of pain
crises.
In contrast
to the high
frequency
of
priapism
following
large doses of parenteral
testosterone,5
this complication
did
not occur
in any of our adult
males
receiving
oxymetholone.
However,
our
patients
were
probably
sodes
were rare
These
findings
of selected
less
likely
prior
to their
demonstrate
patients
with
to develop
crisis
androgen
treatment.
the potential
value
sickle
cell
disease
or priapism
since
of androgens
when
such
in the
severe
anemia
epi-
treatment
contributes
substantially
to disease
morbidity.
Only
patients
with a low frequency
of crises
should
be considered
in order
to avoid
the increased
incidence
that might
result
from a greater
production
of sickle
hemoglobin.
Few children
are likely
to be
suitable
painful
major
candidates,
crises rather
organ
damage
since
most
of their
problems
usually
result
from
repeated
than from severe
anemia.
However,
adults
with evidence
of
may
be less able
to compensate
adequately
for anemia.
This
applies
particularly
disease
who may benefit
androgens.
The potential
risk of hepatic
quently,
to patients
with
evidence
of cardiac
or pulmonary
from the higher
red cell mass that
usually
results
from
value
in individual
patients
must
outweigh
the real
toxicity
the
initial
that
will
treatment
develop
trial
in about
should
not
10%
of the
continue
for
patients.4
more
If no substantial
benefit
if liver toxicity occurs,
results
in terms
of symptomatology
and
the androgen
used should
be discontinued
Even when
significant
terminated
after 3 mo.
objective
manifestations
improvement
The magnitude
will then
define
the
potential
value
Conse-
than
3 mo.
hematocrit,
permanently.
or
occurs,
androgen
therapy
should
still be
of relapse
in terms
of both subjective
and
allow
the clinician
a better
opportunity
to
of long-term
androgen
therapy
for his patient.
Recently,
cyanates
have
been
found
to increase
the hemoglobin
level
and
decrease
the hemolytic
rate as the result
of carbamylation
of the amino-terminal
valine
of hemoglobin.27
However,
doses
of sodium
cyanate
greater
than
35
mg/kg
produced
clinical
side-effects.27
Combinations
of androgens
and
cyanates
in doses
either
compound
free
of toxicity
for both
agents
may
provide
superior
results
than
alone.
ACKNOWLEDGMENT
The
authors
Blossom
are indebted
Zanger
kindly
to Brenda
referred
three
Doherty
patients
and
for
Eloise
blood
Smith
for
volume
their
technical
assistance.
Dr.
studies.
REFERENCES
1. Sanchez-Medal
L,
in
Rico
the
Blood
MG:
treatment
34:283,
L, Gomez-Leal
Anabolic
of
1969
acquired
androgenic
aplastic
A, Duarte
2.
steroids
shek
anemia.
anemia.
Allen
W:
DM,
Fine
MH,
Oxymetholone
Blood
3. Gardner
32:83,
FH,
Necheles
TF,
therapy
in
Dameaplastic
1968
Nathan
DG,
Pringle
JC:
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
TREATMENT
FOR
erythropoiesis.
N
OXYMETHOLONE
Androgens
and
274:420,
metholone
R,
logical
B,
anaemia.
in sickle
Finch
Intern
CA,
Deubelbeiss
JW,
G,
JW,
Harker
RS,
A,
Giblett
Medicine
10.
49:17,
Alfrey
Studies
CP,
of iron
J Lab
Clin
11.
Med
Donohue
ER,
Pirzio-Biroli
51Cr
as a red
19. Gross
sickle
cell
1974
in
Cook
Mar-
5,
ER:
Ferrokinetics
using
73:405,
1969
DM,
G,
Br
RA:
V,
Giblett
Finch
Erythropoietin
MW:
androgens.
excretion
J Lab
Lab
Schulman
on
marrow
Clin
14.
Med
Sproule
Med
failure
and
82:438,
1973
BJ,
25:629,
by
study
of
with
J Clin
Invest
37:486,
15.
Leight
L, Snider
lems
HK:
sickle
cell
24.
cycling
J
1204,
TH,
Ann
studies
10:653,
1954
GO,
in
sickle
steroids.
Byron
5,
effects
EA,
Sci
of hemoglobin
by certain
Promelli
Wenig
actions
of
Nat
Effect
of haemopoietic
Acad
5: Stim-
in chick
5 B androstane
Proc
erythro-
Granick
synthesis
JW:
J, Katz
on
149:3 18, 1968
A,
Kappas
and
blasto5 B preg-
Sci 58:985,
of
1967
steroids
stem
cells.
on
the
Nature
228:
1970
Gorshein
D,
pa-
tion
induced
by
Br J Hematol
A:
for
654, 1974
Hait
WN,
Rapid
Besa
stem
cell
19-nortestosterone
EC,
Jepson
differentiadecanoate.
26:2 15, 1974
Gillette
Cerami
ment
Intern
14:611, 1968
Miraud
RD.
FH:
cell
erythro-
Ann
DG,
Androgen
Gardner
Hel-
CH:
syndromes.
of
Nathan
N Y Aced
Levere
27.
Clifford
ED:
JH,
variants.
I, Smith
erythrocythaemic
AS,
A
WF:
in
its
FH,
The
iF:
Br J Haematol
in
1958
Hemodynamic
Circulation
and
55:
1962
Gordon
25.
alterations
disease
Pathol
hormones.
23.
26.
cardiopulmonary
J Clin
Stimulation
androgenic
Gardner
nane
following
anemia.
Miller
referchildren
1960
BJ:
57:917,
derms
excretion
ER,
studies
and
haemolytic
androgen.
1967
hemolytic
Halden
tients
anemia.
in man
70:777,
in
133:624,
volume
children
congenital
Kennedy
Med
1:249,
Ruchelman
R: Erythropoietin
13. Alexanian
bone
Clin
Med
as a blood
ME,
20. Erlandson
ulation
WK,
1974
JC: Comparative
weight
Am
poiesis.
CA:
J Haematol
R, Vaughn
5, Godel
anemia.
R, Zanjani
1955
12. Alexanian
in sickle
Hemolysis
Intern
sickle-cell
Cummins
scanner.
AG,
Viranuvatti
tag.
Arch
PN:
with
poiesis
in
Hettig
a linear
Motulsky
Gillette
in normal
22.
kinetics
J Lab
133:565,
standard
21.
Adamson
EC,
oxygen
transport
Med
ence
Pediatrics
JD,
DD,
Slichter
Lynch
Oxygen
TA,
and
Studies
1961
K,
disease.
662, 1971
Erythrokinetics
Funk
Blood
cell
Intern
disease.
of height
1970
Jr,
cell
of
WN:
1974
therapy.
175:1164,
LA,
Hillman
Ganzoni
man.
WD:
CA,
Finch
1970
133:698,
JAMA
PF:
Arch
cell
Jensen
in sickle
1967
Bensinger
sickle
cell
1962
of anemia.
Eschbach
18.
Erythrokinetics
treatment
Noyes
sickle
durabolin
Med
70:480,
17. Milner
haemato-
in
PA,
curves
cell anemia.
7:389,
after
5: The
Arch
diagnosis
Bromberg
Clin Med
Oxy-
of bone
The
AM:
10:196,
7. Charache
anemia
androgens
anemia
C:
1972
FH:
Frumin
Research
anemia.
the
40:353,
J Haematol
ii,
cell
Clinical
saglia
for
to
Scand
Boada
J, Alfrey
Gardner
response
9.
Nadell
failure. Blood
Lundh
8.
16.
J Med
dissociation
treatment
marrow
6.
EngI
1966
4. Alexanian
5.
777
SICKLING
PN,
Sodium
sickle-cell
Peterson
cyanate
disease.
CM,
Lu
as potential
N EngI
J Med
YS,
treat290:
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1975 45: 769-777
Oxymetholone treatment for sickle cell anemia
R Alexanian and J Nadell
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