From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
Idiopathic
Hypoprothrombinemia
Hemorrhagic
Diathesis,
By
and
B. LEY,
ALLYN
C.
W.
Associated
M.D.,
the
Effect
G.
GEORGE
M.D.
SORENSON,
of
Vitamin
K
M.D.,
READER,
S.
RALPH
AND
with
PH.D.
OVERMAN,
P
ROLONGATIOX
OF THE
PROTHROMBIN
TIIE
as measured
by
the one-stage
method
described
by Quick
is usually
associated
with
one
of three
conditions
: (1) a deficient
absorption
of vitamin
K, (2) the administration
of anticoagulants
or (3) liver
disease.
However,
17 cases
have
been
reported,’
-‘5
of the
with
some
prothrombin
Likewise,
strable.
a hemorrhagic
time
diat.hesis,
in which
circulating
anticoagulants
Most
of these
cases were
these
and
classified
However,
it is now recognized
Ac-globulin)’6-’9
may
prolong
that
the
longing
tent.
Few
without
the
prothromhin
of the
time
above
cases
have
recognized
the
others
may
not
have
being
been,
of accessory
conversion
relation
completely
cases
with
associated
the
with
treatment
to
due
to
the
studied
to evaluate
prothrombin
and
oil
soluble
previously
in regard
the
the
New
York
and
preparations.
use
them
acces-
or
factors
2 of
the
some
of
all in order
prothrombin
to
times.
hypoprothrombinobservat.ions
of synthetic
In addition,
con-
and
t.o present
on the
demon-
to the
exact
fact.or
time.
Although
to consider
tendency
particularly
K
cases
1 (fig. 1). P. D.,
to
mont
vitamin
reported
Case
muitted
a hemorrhagic
lacking.
prot.hromhin
hypoprothrombinemia
it is important
of t.he condition,
were
factors
(factor
V,
rate,
thereby
pro-
emphasize
the difference in factors in cases with prolonged!
It is the purpose
of this report
to record
2 cases of idiopathic
emia
a prolongation
conditions
fibrinogen
deficiency
were not
as idiopathic
hypoprothrombinemia.
direct
been
and thus
it is impossible
for the observed
prolonged
as not
usual
a deficiency
prothrombin
sory
factors
responsible
were
associated!
three
on
water
soluble
a classrncation
of the
is suggested.
a 29 year
old,
truck
married
in December
Hospital
driver
1947,
of
parentage,
Italian
complainsing
of bloody
was
urine
for
adthree
Iss.
Present
Illness:
He
1943 but w-as rejecte(!
urinsary
findings
revealed
(!iet
military
h)ut. feeling
albumin,
caused
ins apparent
was
for
no
good
dut.y
red
improvemenit
blood!
of his
he
cells,
urine,
when
repeated
w-ell,
entirely
w-hite and
health
after
examined
and
In
a local
consulted
was founsd
to
selective
1946,
physicians
A spice-free,
casts.
which
for
urinalyses.
be
service
ins
curious
about
‘the
whose
urimsalyses
low-proteins,
abnormal
on
low--salt
repeatedi
ex-
aminations.
From
College,
Aided
the
Departmnent
New
York,
by
gramsts
Foundation,
the
the
Americans
Submitted
Special
interest
N.
from
Lillia
the
New
the
H.
Kress
Samuel
Babbitt
Hyde
Cancer
Society.
December
28,
acknowledgment
and
of Med!icinse,
helpful
‘ork
Hospital,
Cormiell
Unsiversity
Medical
Y.
1950;
is
criticism
accepted
the
the
the
Julius
for publications
due Dr. David
in
Foundations,
Foundation,
preparatioms
740
P.
Barr
of
i)r.
report.
amid
Hampil
February
and
this
Albert
W.
Irvinsg
28,
Mary
Lasker
Founsd!ations
and!
1951.
S.
Wright
for
their
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
LEY,
Nine
months
quiring
tice
For
urine,
nocturia
red
casionally
aching
Three
This
before
suture.
admissions
the
msext
right
weeks
before
examination
READER,
from
the
right
the
next
four
a tooth
six
three
to
Paimi.
admission
the
orifice
and
(lays he received
right
symptoms
calf. These
diagnosis
of phlei)itis
I
adivised
bed
He
retrograde
blood!
of
paini, swellinsg,
in h)ed
PD
dlay,
for
1000
1)uring
At
who
next
week
D’MENADIONE
0
issuing
present.
j)enicillins.
the
oc-
(Ionic.
be seen
physicians
mso-
and!
about
ansd tensdermsess
seems by ansother
remained
to
were
could
was
insjectionis
re-
began
l)yelograms
that
hydromsephrosis
achinsg
rest.
the
two
amid he was
bleedinsg
durinsg
but
amid!
swelling.
he developed!
l)rofuse
frequency
right
tablets
by
thsens
normal
a slight.
progressed,
and
PATIENT
that
followed
but
and
was
741
asymptomatic
nsight,
cystoscoped!
‘‘sulfa”
this time he first
noted
periorbital
Tw-o w-eeks before admissions
each
bladder
OVERMAN
was
remained
times
he was
that
ureteral
he
four
AND
extractions
months
flamsk
indicated
SORENSON
of the
made
with
a
sub-
BISULF
‘VITAMIN
K1
OXIDE
l11Itrh11TnTn1ffnTIrni1IlIIIIIIUnllIII
000
(3.
600
200
>
COJ’FRACTI
P2GM.
5
FIG.
I -Undiluted
sidemice
of
his
had
of his
joints
w-hen
he
chills
Past
three
about
ansy
work
of these
Examimsat
did! not
appear
4 cm.
the gums.
There
generalized
this
lost
about
to The
parents
of the
no
35
having
treatment
transiemit
recent
arthsralgias
finger
his
he
tise occasional
on the Urology
w-as nso history
joints.
gums
msotedl
had
He
bled
arm apparemitly
Passage
of clots
Service.
of any
1.
ins all
and! wrist
weeks
admissions
of Case
abnormal
ins isis
bleed-
family.
save
occasional
he
slight
exposure
ill.
ins diameter
He
over
various
a muscular
was
the
right
aniline
l)ut
hip
not
dye
present
pale.
amid there
hemorrhages
was
of “walking
headaches
and
with
pneumonia”
from
(lusts
amid us-ell-nsourishedl
sallow-
conjunctival
lymphadenopathy
for ani episode
migraine-like
to
pat ienst was
no
Ins
and
and
of the
before
York
Hospital
Italian.
There
and
us-crc
begami
swelling
weeks
us-as unremarkable
had
30
times
w-eight.
tw-o
ins 1942
materials.
ions: The
time
right
hip.
hematuria
Newu-crc
25
DAY
transient
on his
of the
particularly
about.
A mild
amid
20
prothrombimi
d!uring
and
memh)er
This
duration
of his
constaimsers
Physical
chymosis
fever
teeth,
plasma)
though
ecchymosis
persistence
History:
w-eeks
the course
who
h)ut
was a(lmitted
I’Iistorv:
The
mi
5
HOSPITAL
cent
definite
nor
his
tendemicy
per
symptoms,
msotedl
large
of the
urine,
he
Family
able.
leg
i)rushed
spontaneous
Because
ing
(100
arid
mseither
10
There
age
through
the
rubbery,
fundi
adult
us-as
a fading
were
freely
hamidling
younsg
us-ere traces
of
18 to 26. In
male
of dried
not
movable,
ccblood
remarknon-
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
742
IDIOPATHIC
tensder
msodes
anterior
about
2 cm.
numldl posterior
The lungs
amid
iso
ins the
left
joinits.
was
deep
heart
nor
wrist
geal
four
fine
and
to
msant
cells
regard
2+,
Stool
guaiac
Serum
hiiliruhins
flocculations
C
ssas
mg.
cent).
Serumn
mins
us-crc
The
and
miodes
in
abdomen
was
of
proximal
elbow-s
and
the
regions.
limitation
of the
of the
time
show-ed
he
18.5
red
blood
3 to 4 plus
soft
motion
interphalanshoulders.
There
had
several
mild!
epistaxes,
albumin.
per
cent
blood
cells
per
The
cells
high
blood
of miormal.
varying
1)ouser
urea
Urine
frons
field,
15
occasional
us-as
nitrogens
examinations
22 mg.
for
malig-
negative.
York
City
Departmenst
of Health
These
positive
cent
per
us-crc
up
mg.
per
his
cent
; thymol
with
an
us-crc
considered
as
to
4.5
; ansd
considered
to
per
cent
cent
.
follow-s
be
: Mazzinsi
inconiclusive
ins
course.
units
ratio
(normal
i)romsulfaleims
indicate
; serum
Plasma
hospital
albumin/globulin
turbidlity
to 5 units)
us-crc
7.7
mg.
throughout
Gm.
tests
was
us-as 0.83
130/75.
swelling
w-hich
25 white
and
us-as
(nsormal
These
calcium
level
and
5.5
per
15 units
0 to 5 per
during
urinalyses
10 to
New-
totaled
us-as 0.2
similar
amid femoral
of syphilis.
tests
1)roteins
was
tenderness
movement
anti-complementary.
diagnosis
but
inguinal
Service.
21.6
the
smaller
pressure
slight
fusiform
on
Service,
bacilli
by
slight
and
epitrochlear,
calf.
casts
was
Kolmer
to the
right
Repeated
acid-fast
studies
Kahn
with
axilla
was
discomfort
blood,
test.
each
There
Medical
granular
and
blood
felt.
Urology
the
gross
clearance
Serologic
2+,
to
coarsely
urea
The
normal.
the
on the
field
in the
fingers
Finsd!insgs:
1)0w-er
and
of
in
days
Lah)oratory
The
the
tenderniess
After
in
chains
us-crc
complained
he us-as transferred
high
were
masses
amid all
He
diameter
cervical
the
arid!
organs
in
HYPOPROTHROMBINEMIA
0.328
5 units)
2.9
hepatic
4.2
was
of 3.2/2.3.
to
retentioni
normal
phosphorus
fibrinogen
up
per
cent
(normal
function.
mg.
cent
Gm.
Serum
; cephalimi
per
cemit
3.3
M.,
.
.
The
blood
No
vita-
cryoglohulini
found.
Hematologic
cemst, anal us-hite
monocvtes
Hemoglobin
blood
count
7 ier
forms
32 per
The
Platelet
snsear.
The
cent,
cent
test.
clotting
was
The
0.40
ier
cent,
blasts
S
The
per
cent)
and
differential
count
yielded
was
1)rothrombin
cent.
time
15 secomi(ls)
as
and
65
a tough,
test
at
over
per
per
reduced
ans(I
swollens
misinutes
(nsormnal
clot.
hemolvsis
cent
lymphocytes
cent,
of
3 minsutes
band
and
the
Quick
a 12.5
us-as
marked
per
at 0.40
at
cu.mm.
eosinsophils
blast
forms
cells
1 ler cent.,
1 per cemst.
us-as 30.4
saline
0.25
(nsormal
metamyelocytes
cent
10
tournsi-
complete
cent,
method)’#{176}
on
on
5 to
The
22 p
8 Per cent,
reticuloendothelial
cent.
beginning
(control
5 per cemst,
forms
band
us-as 2.4
retracted
show-ed
0.25
cenit,
cent,
coumit
a total
count
of 78,000
cells
per
ler chamber
(normal
5 to 20).
prom-elocytes
15 per cent
over
formed
follosvs:
(modifications
slightly
usas
29 )er
12 per
44 per
reticulocyte
method)
complete
9 per
13 per
normoblasts
The
.
appeared
blood
hematocrit
; lymphocytes
polynsorphonuclear
fragility
not.
polvmorphonsuclears
myelocyt.es
censt,
(miormal
the
coumit.
differential
cent
platelets
hours,
blood
mature
3-tube
marrowaspirat.iomm
and 20 megakaryocytes
marrowmature
1 per
Thse crythrocyte
negative.
(control
cells
the
red
following
cent,
(Lee-’VIsite,
eighteen
Gm.,
the
4 per
and
150,000
tinne
per cent).
Sternal
50,000
to 150,000)
cent,
usas
11.6
with
eosinophils
oms standing
per cent
us-as
5,200
amid! unclassified
count
minsutcs);
(luet
1)ata:
2 per
19
seconsds
erythrounidiluted
(Iilut.ion
(nsormal
42.2
seconds).
Course:
The
evidensced
and
by
into
the
to a day
patienit’s
arid
urinse.
the
by
ins (loses
by
in amnounsts
On
axilla.
use(l
heat,
the
further
up
durinsg
the
gums
His
and
up
to
t.o 1500
the
and
288 mg.
day
hospital
heniostasis,
operation.
per
efforts
nil. per
had
day
topical
Pathologic
nose,
transienst
elbows,
redlness
therapeutic
twenty-sixth
Meticulous
course
the
by
into
arthralgias
anskles
persist.emit
the
the
effect
day.
The
as noted
effect
no appreciable
an
enlarged
thronibin,
examinations
lasting
of
still
Frequenst.
effect
lymph
amid
transfusions
of the
sections
of the
five
(loses
of
removed
of tise
fresh
us-hole
is
blood
time.
from
node
of
menadiomie
of
prothrombins
of fresh
100
useeks
parent.eral
from
transfusions
us-as
hours
hamids
(umidilute,
first
time
larger
ons the
node
the
skins,
a few-
joints
determinsations
as
amid
from
int.erphalangeal
18(1 secon(!s
durimig
ons the prothrombimi
belous.
bleeding
retinae,
continued,
and!
to over
generalized
comsjunctivae,
sus-ellinsg.Pnothrombins
ranged!
from
29.0 seconds
There
us-as rio demonistrable
cent
plasma)
hiospitalization.
mensad!ionse
from
involving
stools
or two,
amid! accomnpansied
clouded
hospital
bleeding
the
1)100(1
show-ed
left
us-crc
corn-
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
LEY,
plete
obliterations
arid!
of its
numerous
findings
spite
For
the
amid
throat
On
first
of severe
ness
us-crc
began
to
and
l)rothroml)irs
The
further
During
givers
900
daily
output
mnl.
fortieth
day
edema
latter
ing
was
this
1)ccame
of
sodium
to
slurred
ml.
of
received
a fall
given
432
coniplained
in blood
pres-
shifting
dull-
and
us-ith
subscquemst
the
his
two
by
days
were
and
The
us-as
16.0
to 19.5
There
us-crc
nso
urine.
was
solutions
us-as
developed
and
120
of
He
infusion
per
on
the
edema
cent
and
The
glucose.
disoriented,
On the
his
cent
distress.
of 20 per
signs.
intra-
us-as then
thereafter
rng.
respiratory
stuporous,
neurologic
ml.
a generalized
consequent
an
Ins spite
350
and
morning
1)ur-
his
speech
of the
forty-
died.
right.
fluid.
no
cent.
He
confused,
no localizing
comatose
mug.
treatment.
from
limits.
day
which
w-ith
and
became
Passed
a 4.07
later.
tract
varied
normal
following
niitrogen
epinephrine
patient
us-ithin
the
urea
of the
days
I ,0()0
ans(I Davidsoms.2’
completion
five
amid
obtained!
hematuria.
mi
blood
cent
the
patient
output
was
MacDonald
amid left
The
pleural
peritoneal
comstaimie(l
spaces
cavity
contained!
300
respectively
3,000
ml.
of
(lark
blood.
The
spleen
farcts.
association
nsated
clot
w-hich
liver
weighed
225Gm.;
the
left
240
lungs
us-crc
heart.
weighed
anterior
in
and
in
the
matter
at
the
in
Case
the
the
lupus
degree
marked
bone
with
2 (Fig.
Vitamnin
left
marrow.
pale
the
fibrinoid
This
arterioles
of
cell
The
i)onc
cytoplasm
a 40
kindlly
year
together
staine(l
tw-o
to
weighed
925
left
ventricle.
of the
There
w-as
surface
infil-
and
there
four
times
us-as
also
The
Gm.
The
the
mi
a hemorrhagic
running
There
cut
focally
yellowish-w-hitc.
hemisphere
pedunclc.
weighed
On
us-crc
appeared
The
kidney
and
blood!
general
infarct.
cerebellar
diegemierations
insdistinguishahle
plasma
was
necrotic
lami-
into
the
a smaller
white
hemor-
hemisphere.
extensive
erythematosus.
in
in
in-
a large
hemorrhage.
right
diffusely
us-crc
surfaces
amid
a small
right
pelvis
several
us-as
petechiac.
1)0th
hypertrophy
cerebellar
cerebellar
kidney
2). G. K.,
K1 oxidle
of
us-ith
was
nodes
cut
show-ed
there
The
flecked
and
moderate
us-as
congested.
cortex,
edematous,
was
middle
wmts an
The
arid!
portion
the
us-crc
organ,
intraperitoneal
and
lymph
color.
arsd
of the
massive
calyces
The
in
there
the
firm
t.he
hypophysis
of
of
disseminated
a rather
the
of
The
hyperplast.ic
surface
surfaces
pelvis.
and
There
lobules
extensive
left
Gm.
level
infarct
us-as
the
posterior
Microscopic:
less
cortical
congested
of
site
particularly
red-brown
415
infarct
the
and
the
on
moderately
tissue.
moderately
portion
anid the
karyocytes
The
but
blood
firm,
erular
Gm.
be
us-as
yellowish-white
clotted
enlarged,
rhagic
and
congested!
of these
to
Gm.
was
one
appeare(l
parenchyma,
usith
Gm.,
with
1,930
entire
trated
550
weighed
In
was
usith
us-crc
by
next
remained
however,
relieved
bloody
the
microscopic
respiratory
Findings-Gross:
350
unclotted
the
per
there
and
for
His
after
for
intravenously
upper
became
to
day
ml.
the
but
he
patient
wave
Km oxide*
described
hours
times
sulfate
the
l)lood
fever.
a fluid
plasma
vitamin
method
one-half
fell
each
2000
however,
Autopsy
and
except
96 mg.
of
amid
woumid.
he sudldcnlv
shock
and
the
the
d!ay
biopsy
Repeated
tise
39 C.
for
day,
inito
rigid
1)100(1
to the
day,
over
wemst
became
oil-soluble
also
ml.
substantially
day
amid
*
time
4,000
fell
time,
second
one
bleeding
of
was
marked
day,
thirty-eighth
fluids
following
hospital
quickly
us-hole
prothrombin
of
the
venous
done
clotting
the
phagocytcs
cells.
The
conditions.
same
daily
evidences
and
according
time
and
again
from
38 and
rio cause
thirty-eighth
ai)dorncn
of
general
the
intravenously
secomids.
the
oozing
of betuseens
revealed
ansd
pain
hours
Transfusions
ins his
seconds
day
large
gianit
lymphadenitis.
considerable
runs a fever
On the
abdominal
two
chronic
us-as
examiniationss
hospital
midnight
given
17.0
repeated
intraveniously.
detected.
About
A
l)atient
Within
imnprovement
of atypical
the
time
genseralized
to 85/40.
those
there
thirty-seventh
sure
be
743
OVERMAN
of hennorrlsage.
Occasionsal
us-crc no Recd-Sterniberg
There
taken
nsg. of mnenadione
ssere
to
AND
areas
present.
precautions
cultures
the
with
were
considered
of the
SORENSON
architecture
eosiniophils
us-crc
In
READER,
the
in
fibrinoid
liver,
infiltration
supplied
Jewish
spleen
the
female
by Mr.
the
and
the
the
mansy
bookkeeper
William
J.
heart.
of the
1001)”
also
lymph
In
to
there
the
spleen
sus-ollcn
to
and
of
a much
add!ition
nodes,
admitted
of Merck
glom-
lesionis
noted
abmsormally
us-as
Reilly
collagens
“wire
us-as
kidneys,
contained
nuclei.
the
of
fronn
degeneration
the
in
marrowalso
and
pyknotic
old
places
megathe
New
Compamiy.
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
744
IDIOPATHIC
York
of
Hospital
ten
for
days’
for
usas
Illness:
incidental
about
cent.,
abnormal
Ins
years.
red
she
shoulder.
tw-o
or
10.7
three
was
42,000.
and
of
activity
and
then
was
3.4
had
M.,
bleeding
of
complainimig
severe
time
(Duke)
fibrinogen
not
rectal
PATIENT
w-it.h
us-as
8 minutes;
2 G
the
in her
bleeding
rectal
After
as
The
knees
amid
on
her arms
right
arm
amid
amid legs for
Her
hemoglobims
platelet
count
1 to 5 minutes);
the
clottimig
24 hours
us-as
normal
there
was
positive.
were
poor
rc-
Prothrombimu
although
stools
hemoglobims
differential.
The
test
reported
Her
a normal
bleeding.
(normal
today.
repair
of a ventral
occasiomsal
bleed-
differential.
tourniquet
us-crc
used
with
feet,
a normal
10 minutes).
The
those
in
the
with
present.
6,100
intermittently
increase
clot.
as
ions.
paimis
10,600
concentrations
as accurate
operat
appeared
5 to
fragile
count
some
(normal
abnsormally
us-crc
been
at
for
were
blood
joint
had
in 1934
hemorrhoids
hemorrhoids
w-hit.e
of
W.B.C.
34 mimiutes
an
internal
msoted
red spots
there
R.B.C.
(Lee-White)
tract.ion
use
1949
to the hospital
she had
had
M.,
because
small
The
3.5
admitted
years
and
count
tendency
us-as
Gm.,
admittedl
us-as that
External
blood
Transient
was
in January
time
us-as first.
complaint
i)leeding
1937
time
She
three
75 per
No
eighth
duration.
Present
hermsia. An
ing
the
HYPOPROTHROMBINEMIA
the
grossly
methods
bloody.
in
A diag-
K
101
D.MENADIONE
80
BISULF.
VITAMIN
o
6
I0
4
K1
OXIDE
a.
2C
z
2
0-i
0
‘6OC
rfJ1it
..‘
5
of idiopathic
thrombocytopensic
appeared
normal
from
350,000
to
to
the
4.2
hemorrhoids
M.
Tus-o
with
w-ecks
abscess
in
normal
and
The
April
noted
M.,
W.B.C.
us-as
i)and
forms
4 per cent.
us-as
240,000,
yielded
and
the
us-as
free
50
55
60
65
amid treatment
and
The
test
with
readmit
Bleeding
of
a splenectomy
platelet
became
was
count
miegative.
transfusions
the
her
her
clinic
of
visits
and
in
the
rectum.
the
Case
2.
done.
The
postoperatively
The
1)lee(ling
red
her
one
differential
bleeding
acid
time
was
prolonged;
after
histamine.
slightly
but
in
1)lood
count
pit.ting
and
legs
and
per
rose
retraction
and
of
us-crc
she
was
seems
cons-
edema.
intolerance
t.o cold.
13.4 Gm.,
R.B.C.
polymorphonsuclears
monocytes
index
us-as
the
tourniquet
us-as
good
anemia
of a small
count
fragile.
ankle
us-as
mat.ure
cent.,
Volume
draimiage
platelet
1938
had
count:
Pernicous
was
hemoglobin
3 minutes
clot
and
visit
arms
Her
and
time
clot
thereafter,
on
pains
follow-ing
clotting
although
ankles
from
ted for incision
time,
retraction
in
was slightly
no
made
13 per
cent,
lymphocytes
57
The smear
show-ed
macrocytosis.
the
time
us-as
sui)side,
she
clot
in
bleeding
us-ith
45
tinies
examination.
the
tourniquet
wound.
complained!
10,500
The clotting
discharge
pain
she
-..,,
40
prothrombims
purpura
to
irregular
occasional
‘.,‘.,
35
DAY
hemoglobin.
good
occasional
cent,
eosinophils
analysis
this
us-as
1940
She
count
there
of
cent.
-,.
plasma)
on histologic
490,000
and
splensectomy
pat.ient
plaining
In
after
the
cent
appeared
84 per
-.
25
30
HOSPITAL
20
(100 per
spleen
ranged
from
..
15
2.-Unsdiluted
FI;.
nosis
10
us-as
15
11 per
cent
and!
1.44. The
platelet.
test
w-ith
2.9
a firm
suspected.
was
positive.
clot.
Gastric
The
patient
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
LEY,
refused
to
take
knowms amount
During
this
parenteral
liver
of liver
by mouth.
period
nsosed as chronic
userc
amid
svas
Her
1943
the
isemoglobin
rectal
bleeding
to
at intervals,
Ten
amounts
nsor
and
her
R.B.C.
ferrous
1940
for
an
ranging
sulfate
omi her
timothy,
face
dog
and
which
an
uns-
w-as
diag-
and
(lust
epithelium
acute
sinusitis
w-hich
subsided
quickly
used.
between
3.0
and
4.3
M.,
the
hensoglobins
returned
she
in
the
to
same
times
a nosebleed
mild
the
a day.
She
lasting
all
M.
had
levels
no
of
in her
1949
1.7
She
previous
the
January
several
had
dropped
us-as inconstant
approximately
admission
rectum
by
R.B.C.
to
but
showed
the
her
a hemorrhoidectomy.
3.0
clinic
to
for
became
to
very
day.
She
4.0
M.
She
next
pass
con-
counts
five
and
noted
of
years.
considerable
fatigued
had
Gm.
Blood
the
began
3.8
significant.
visits.
anemia
patient
with
further
no
pale.
On
ecchymoses
hematuria.
History
the
node
History:
age
at
bramies
uscre
pale.
blood.
There
shotty
history
of any
abmiormal
trace
and
bleeding
in any
member
the
bleeding
and
2 cm.
a cholecystectomy
age
22 was
contact
w-ith
nor
size
The
tests
serum
for
site
had
and
to
had
have
of
colds
a cervical
cholesterolosis
been
chemicals.
frequenst
drainage
for
said
prolapsed
the
of the
follow-ed
The
The
right
us-crc
systolic
margin.
by
dietary
exces-
history
us-as
us-crc
encrusted
cervical
The
murmur.
There
nares
posterior
clear.
poorly
nourished
and
mucous
menus-
skimi
heart
us-as not
A firm,
us-ith
chain
a
enlarged;
nontender
us-crc no other
and
liver
was
abdominal
masses.
adnuission
showed
hemorrhoids.
uncatheterized
syphilis
protein
thymol
turbidity,
alkaline
phosphatase
urine
blood
cells
specimen
and
us-hite
obtained
blood
us-as
us-crc
5.3
on
but
cells,
subsequent
speci-
negative.
Gm.
bromsulfalein
per
cent
retention,
determinations
with
an
albumin/globulin
cholesterol,
us-crc
normal.
The
Hematologic
with
the
Data:
follous-insg
300,000 and the
minutes;
clottinig
test
cells
per
to
of
3.9/1.4.
and
bilirubin
flocculation
was
12 unit.s
3 units.
4.0
mg.
us-as 0.308
per
Gm.
cent.
per
The
cent..
blood
No
cryo-
founsd.
polymorphonuclears
normnoblasts
4 per
tourmuiquet
esters,
cephalin
(normal
up to 5 units),
but
gradually
fell
Serum calcium
was 7.7 mg. per
cent; serum phosphorus
vitamin
C level us-as 0.58 mg. per cent. Plasma
fibrinogen
us-as
ratio
cholesterol
oni admissions
globulin
life
petechiac.
in
lungs
apical
costal
red
incision
12 and
in
nodes.
a few-
her
at
ecchymoses
blowing
An
of
an
us-as a slender,
underdeveloped,
moderately
acutely
ill. The
and
right
had
normal.
Serologic
Total
17,000
tendency
rarely.
patient
no
All
She
of
taken
nodes
loud
albumin
age
history
was
inguinal
Findimigs:
us-crc
no
were
a moderately
of
robust.
media.
at
several
5 cm.
below
us-as a ring
of
never
A tonsillectomy
There
us-crc
Laboratory
w-as
ions: The
chronically
axillary
was
mnens
otitis
alcohol
Exanuinat
appeared
there
and
us-as
and
Physical
ss-oman
who
palpable
There
20.
There
abnormal
few
no
appendectomy
age
bleeding.
not
was
patient
sinusitis
9, an
bladder
sive
The
by
at
gall
: There
family.
Past
4,900
ferrous
injections.
were
for
sulfate
admission
conil)licat.ed
a
oak,
desensitizing
increased,
readmitted
blood
of
Family
of
bleedinig
before
of
day
of
R.B.C.
take
rash
ragweed,
; nio sulfonamides
the
did
erythensatous
ins September
was
however,
days
an
w-ith
a series
she
take
had
she
745
OVERMAN
Gm.
rectal
and
tinued
the
11.4
AND
although
tests
received
again
ansd
extract
Skin
continued,
9.0
SORENSON
Patient
treatmemit
anemia
Ins
she
admitted
omi conservative
betweens
the
urticaria.
positive
She
READER,
24
cemit..
Hemoglobin
(lifferemitial:
was
5.5
lyniphocytes
per cent,
The
band
us-as
cu.
miegative.
mm.;
forms
reticulocyte
platelets
appeared
time (Lee-White
Sternal
3
adequate
tube) 30
marrow-
one megakaryocyte
2 per
cent,
cent
and
us-as
cent,
metamyelocyt.cs
2 per
censt.
The
on smear.
minutes;
aspiration
bleeding
t.he
clot,
showed
7 per cent,
promyelocytes
normoblasts
The
and
per chamber;
3 per censt,
mature
polymorphonuclears
11 per
cent,
myelocytes
10 per cent.,
3 per
R.B.C.
1.4 M.,
hematocrit
45 per censt,
monocytes
8 per
22 per
count
phils
locytes
erythroblasts
Gm.,
the
lymphocytes
band
24 per
forms
5 per
cent.
platelet
time
retraction
follousing:
20 per
17,
cent,
W.B.C.
mature
1 per cent
count
(Duke)
and
us-as
us-as
normal.
total
cent,
The
count.
cosino-
14 per cent,
metamyccent,
procrythrohlasts
3
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
74(1
IDIOPATHIC
The
prothronil)in
nsiinsutes
Course:
but
time
Use
on
12.5
Ins the
conlt.inue(!
to
decrease,
of
muienadione
the
pass
of
no
repeated
mug
and
stopped
and
of the
of
later
the
prothrombini
the
nsext
Four
The
days
patient.
after
total
no
thrombin
times
She
conutinucdl
to have
pertinent
to
elucidatiomi
Special
of
the
us-crc
the
and
the
us-ith
from
decrease
wa
themi
of
the
mg.
ins
givemi
urgenscy
imstravensously
The
pathologic
on
noted
cent
()
Because
therapy.
cells
the
discharge,
for slight,
ins her physical
3.2 M. atsd
Gm.
per
unchanged
and
rectal
bleed-
diagmiosis
us-crc
the
seen.
sixty-eighth
onset
of
periorhital
11cr
with
chronsic
wound
healed
hospital
she us-as readmitted
edema
about.
the
examination.
W.B.C.
9,000
was
The
day.
amid
for
eyes
urine
msormal
depeisdent
evaluation.
and
in the
She
amskles
normal.
differcmutial.
Her
The
was
Liver funsction
an A/G
ratio
of 4.5/2.8.
those
on her
previous
studies
admission.
Her
pro-
normal.
slight
puffiness
of her
of her
case
us-as
face
ankles.
amid!
obtainsed.
She
No
us-as
additional
discharged
insformnation
after
four
weeks.
Studies
the Quick
one-stage
factors
in addition
Whether
t.he prolongation
a hypoprothromhinemia
the
Case
following
prothrombin
time
to the prothrombin
is a summation
concentration.
of the prothrombin
time in these
2 cases
or to one or more
of these
other
factors
was
was due
determined
to
studlies:
1
1. Effect of Serum:
To rule
fresh
normal
serum
containing
patient’s
the
further
improved
patient
change
R.B.C.
As previously noted,
the effect.
of several
l)y
I)iol)sied
after
Except
of 648
of memsad!ione
administered
blood.
appeared
mansifestationss.
Reed-Sternsberg
diselsarged
5
decreased.
This (lose usas then
decrease
in the prothromnbin
time
us-as a gradlual
usas
over
of
time
produced
hours.
t.hems
without
ml.
1,900
administration
mg.
definitely
hemorrhagic
nor
one week
bleeding.
serum
protein
us-as 7.3
otherus-ise
essentially
us-crc
other
nsodes
discharge
had
reniaine(!
no
us-as
sigmuiflcanst
was
11 Gm.
time
there
1,000
us-as
amid
prothrombin
hours
forty-eight
oxide
seconds)
received
the
intravenous
of
usithimi
K1
days
it
cosinsophils
anskle
edema.
Therefore,
had! had iso more
rectal
there
was
hensoglobins
five
where
lymph
No
unsevemutfully.
vitamnin
patient
seventy-tuso
(lose
16.5
seconsds).
although
The
next
time
fig.
us-crc
the
and
instravenous
prothronssl)ins
axillary
lvmphadcnitis.
the
(control
41.5
admission,
over
A single
there
umudiluted
(control
prolonged.
(loses
range,
seconds
dilution
stools
1 ,000
over
normsial
One
b)loody
markedly
ins the
hours
the
follow-ing
time.
chansge
forty-eight
to
days
ins divide(!
t hse situation,
188
saline
grossly
it. remained!
prothronil)ims
usiths
censt
four
to
us-as
Ier
HYPOPROTHROMBINEMIA
blood.
fibrinogen
The
results
out. a defect
thrombin
are
determination
shown
of 0.328
in
Gm.
in the
but no
second
phase
of coagulation,
fibrinogen
was added
to the
table
1. These
per cent,
indicate
results,
together
with
no defect
in fibrino-
gen.
Blood
2. Effect. of Normal
mixed
w-ith normal
ol)tained are shown
these
blood
in table
on
Patient’s
clotting
and
2. No
Plasma:
times
anticoagulant
The
prolong
dilution.
gest
patient’s
determined.
effect was
plasma
The
was
results
demonstrated
under
condlitions.
3. Effect. of Normal
Plasma
on the Prothrombin
The effect of normal plasma on the prot.hrombin
was
The
were
determined.
The
determination
the
prothrombin
However,
a transient
results
obtained
are shown
on January
26, 1948 did
time
January
anticoagulant
of the
29,
1948
effect
normal
Time of Patient’s Plasma:
time of the patient’s plasma
in table 3.
show
the patient’s
plasma
there
was
of the
patient’s
no
beyond
such
that
effect.
plasma,
plasma
expected
These
although
to
from
data
no
sug-
clear
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
LEY,
interpretation
seems
interest
that
of the
plasma
READER,
SORENSON
justified
Conley,
on
the
et al.22 have
in some
AND
basis
of only
recently
cases
747
OVERMAN
found
two
determinations.
a transient
It
anticoagulant
of hypoprothrombinemia
due
is of
action
or
to dicumarol
severe liver disease.
1.-(Case
TABLE
Patient’s
-
Blood
Normal
Blood
1)
Normal
‘
Serum
2. ml.
0.0 ml.
9 mm.
2.
0.5
ml.
2 nun.
ml.
2.0
ml.
0.0
ml.
Over
2.0
ml.
0.5
nil.
2 mimi.
2.-(Case
TABLE
Normal
2.0
Blood
ml.
0.0
Plasma
90
Clotting
ml.
Time
64mm.
1.OnuI.
0.OSml.
1)
mins.
1.0
0.1
ml.
5
mini.
0.2
ml.
64mm.
0.S
nil.
4
ml.
1.5
ml.
3.-(Case
TABLE
Date
Normal
1-26-48
Plasma
Patient’s
Plasma
0
15 sec.
50%
26 sec.
100%
29 sec.
‘
4.-(Case
TABLE
0
15.4
sec.
50%
16.0
sec.
50%.
0
4. Test
1)
Plasma
Saline
100%
0
for
Accessory
0
0
29sec.
No clot
50%
0
53
50%
50%
has
prothrombin
accessory
normal
factors
(Ac-globulin,
factor
V).’
plasma
contains
essentially
normal
prot.hrombin.
the
prothrombin
if due
Addition
time
to
oxalated
It
remove
no
of such
prolongation
prothrombin
Prothrombin
0
Factor:
from
48 sec.
100%
50%
100%
Time
0
0
Patient’s
Proth.
‘
100%
100%
Plasma
mini.
1)
50%
1-29-48
mm.
S4 mm.
0.Olml.
1.Oml.
BaSO4
Time
1)
Patient’s
1.Oml.
However,
Clotting
been
normal
plasma
that
shown
but
Therefore,
amounts
if it were
deficiency,
due
the
in
24 hrs.
sec.
50 sec.
plasma,
to the
Time
barium
has
to
sulfate
will
effect
on
barium
sulfate-treated
of accessory
factors,
patient’s
addition
little
plasma
accessory
of
would
factor
the
barium
the
but
correct
deficiency.
sulfate-
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
748
IDIOPATHIC
treated
time.
normal
The results
These
plasma
would
of such
tests
results
factors
had
show
no
corresponding
plasma
was
that
more
effect
amount
not
mal:
E.
units
the
ml.).
of
the
effect
4.
on
plasma
prothrombin
No
evidence
time
than
the
defect
of factor
5.-(Case
V deficiency
ml.
0.5
1-6-49
nil.
Plasma
6.-(Case
6.
family
1. Effect
Parke,
of
Plasma
Saline
,
100%
,
Prothrombin
50%
0
17 sec.
17.4
sec.
0
42.0
sec.
16.0
c.
50%
0
.
50%
50%
50%
.
0
0
100%
21 .0 sec.
1
0
100%
0
50%
0
50%
50%
50%
0
w-ithin
the
normal
19.7
sec.
30.7
sec.
16.4
sec.
0
‘
Time
0
0
Thrombin:
2!). 4 sec.
18.0
sec.
time determinauncle)
of the
range.
In
was
together
no
with
defect
obtained
diata
of normal
case
to
thrombin
the
in!icate
plasma.
are
that
the
solution
patient’s
fibrinogen
in fibrinogen
the effect
of thrombin.
Effect
of Normal
Plasma
These
this
added
(Topical
plasma
Thrombin,
with
the
of
0.308
results
as
5.
results,
indicated
results
time
2)
100%
& Co.)
in table
These
The
n-crc
Davis
recorded!
2.
Ssec.
2
Case
iting
Ssec.
Prothrombin
Times
on Patient’s
Family:
The prothrombin
on
5 members
(mother,
brother,
2 sisters
and a paternal
patient’s
cent,
Patient
0
50%
0
.
1-15-49
tions
Patient’s
obtained.
Normal
.‘
50%
50%
1-14-49
a
of
patient’s
Time
________________________
________
TABLE
Normal
addition
2)
Plasma
Date
accessory
in the
was
Clotting
Solution
0.1
prothrombin
cont.aining
indicates
that
the
factor
deficiency.
TABLE
Thrombin
the
Determination:
Prothrombin
determination
by a
method
(Warner,
Brinkhous
and Smith)
was done
(Department
of Pathology,
Columbia
University,
Surgeons).
No prothrombin
units
were obtained
(nor-
and
per
addition
on
Flynn
of Physicians
300
no appreciable
recorded
in table
of saline.
This
to an accessory
due
Joseph
Dr.
College
have
are
the
5. Two-stage
Prothrombin
modification
of the two-stage
l)y
HYPOPROTHROMBIXEMIA
shown
the
on
in
nor
the
table
patient’s
determination
evidence
Prothrombin
of an
anticoagulant
Time
of Patient’s
Gm.
per
inhibPlasma:
6.
plasma
d!idl
not
prolong
the
prothrombin
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
LEY,
3.
Effect
Plasma:
These
of
READER,
Normal
SORENSON
Recalcified
The results
results
show
AND
Plasma
on
the
are shown
in table
7.
no significant
prolongation
are
plasma
the
patient’s
recorded
in table
8.
The addition
of plasma
thrombin
no
on
time
any
deficiency
5. Two-stage
mination
(normal:
of
done
300
units
than
addition
showed
Addition
Plasma
Patient’s
not
obtained
affect
that
the
pro-
there
was
prothrombin
deter-
Plasma
Saline
Clotting
Time
0
0
56.5
sec.
0
50%
60.0
sec.
S0%
50%
0
(iSo
sec.
Patient’s
8.-(Case
2)
Plasma
Prothrombin
Saline
0
100%
0
30.7
100%
0
0
No
50%
S0%
0
59.6
0
50%
50%
in prothromhin.
Therefore,
(mother,
there
in the patient’s
on Patient’s
and brother)
father
ml.
no
2)
S0%
of factor
V (Ac-globulin)
6. Prothrombin
Times
normal
sulfate-treated
results
indicating
two-stage
of recalci-
100%
BaSOm Plasma
members
did
Patient.’s
than
10 units
of prothrombin
per
of factor
V (Ac-globulin)
produced
7.-(Case
TABLE
increase
The
less
The
factors
of
time
of barium
of saline,
factors.
Determination:
Dr. Flynn
per ml.).
effect
Time
clotting
determined.
accessory
the
TABLE
Normal
n-as
containing
more
accessory
Prothrombin
by
plasma
Clotting
of the
fled normal
plasma by the patient’s plasma.
4. Test for Accessory
Factor
Deficiency:
The
normal
749
OVERMAN
appeared
Time
sec.
clot
ins 24
hours
sec.
51 .4 sec.
to be no defect.
plasma.
Family:
The
of the patient’s
prothrombin
family
in the
were
amount
times
within
on
3
the
range.
DISCUSSION
In
neither
vitamin
K,
sufficient.
of these
2 patients
of dhcumarol
or
magnitude
the
is believed
that
Therefore,
it is believed
that
each
without
evident
cause
associated
had a history
of unusual
bleeding
that
indicate
mia.
the
defect
that.
n-as
these
was
other
to account.
for
possible
presence
on
a congenital
2 cases
should
there
evidence
of dleficient.
poisoning,
or of liver
the hypoprothromhinemia.
of circulating
anticoagulants
drug
of these
2 cases
with a hemorrhagic
in childhood
and
basis.
be classified
Therefore,
had
absorption
of
dysfunction
of
Furthermore,
it
n-as excluded.
a hypoprothrombinemia
tendency.
thus
there
the
as idiopathic
Neither
of them
is no indication
experimental
hypoprothrombine-
results
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
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From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
752
IDIOPATHIC
To classify
thrombinemia,”
accurately
the
it is essential
prothromhin
information
deficiency
is not available
a
familial
incidlence
laboratory
data
of
“idiopathic
t he
either
(2)
and!
only
time
previously
reported
in adult
or
tendency
and
abnormal
appearing
of accessory
of the cases
abnormalities
cases
(table
may
he
or
appears
the
to fall
into
the
is no
times.
first
Such
The
to he a differential
becomes
members
, however,
the
: (1)
prothrombin
tendlcncy
should!
that
groups
he further
apparent
hemorrhagic
and Quick,#{176}
separated
since
the defects
in each
of them
were clearly
concerned
uuith an accessory
factor
rather
than
with prothromhin.
The 2 cases of the present
report,
the characteristics
of the ‘ ‘acquired”
group.
There
\VOI1l(l seem
to be considerable
doubt
whether
the “acdluired”
truly
definite
no
widespread!
ent.
1 of this
and
report,
or medications
particularly
pitalization
deficiency
The
bleedling
in
What
he
is
l)ut
the
edema
indbcate
is probably
the
pathogenesis
of
part
his
a
in
anemia,
persistence
final
illness
generalizedl,
the presence
of
a generalized
only
another
the
varied
anemia,
the
defect
may
pathologic
joint
idiopathic
hypoprothromhinemia”
must
await
of
the nature
and
metal)olism
of prothromhin.
however,
that. of the 5 cases
reported!
(includling
understanding
significant,
report)
410.
12
have
case7 was given
only
(Synkamin).
Whether
point
of differentiation
respondled
to
massive
Quastler
doses
unlikely,
his hosprothrom-
symptoms,
the
i)e and
by
and
most
and! perhaps
of vitamin
K1
skin
hypopro-
what
states presented
of
of Austin
lesions
t.o the
of which
2 patients,
patient
that
the
response
preceded
that
the
hears
the
of an
from
seems
defect
“acqiliredi
lesions
distinct
though
obscure,
disease.
of normal
prothrombin
dlisease
process
manifestation.
of the prothrombin
the apparently
to
The possibility
hypersensitivity
Quastler.
abnormal
during
generalized
were quite
evidence
of renal
disease
which
years.
In Case 2, it also appears
and!
and
and!
an
received
a
tendency
1937,
lesions
and!
thrombinemia
the
of Austin
arisen
as
in view
of the
by at least four
bin
activity
the autopsy
also revealed
pattern,
which,
however,
unrecognizable
that
found!
in the case
in Case
1 could
have
blood
group
an
In Case
obscure
clotting
possess
“idiopathic”
hypoprothrombinemia
or even
a single
or
(liSease
entity.
Of the 3 cases previously
reported7’
12 2 n-crc
found
to
other
significant
abnormality.
In the third
case,
autopsy
disclosed
a
granulomatous
disease,
the precise
nature
of which
was not appar-
represents
have
a
time,
becomes
evidence
of familial
The cases of On-ren8
group,
include
manifest
in the early
of the family
demon-
of
bleeding
in which
there
prothrombin
factors.
literature.
9) dloes suggest
divided
into
two
a prolongation
in which
clotting
in the
of the reports
do not
with
hypoprothrombinemia.
the bleeding
tendency
in most instances
other
form,
years
manifestations
although
in which
in which
acquired
cases
of “idiopathic
hypoprothe diefect
could
be ascribed
to
hut again
the majority
relatives
of the patients
a bleeding
an
reported
whether
or to a deficiency
in the majority
hypoprothrombinemia”
congenital
form,
years
of life an(1
strafe
previously
to know
of prothrombin
of value,
on
the
characteristic
Review
HYPOPROTHROMBINEMIA
by
relation
by these
other
cases
more
complete
It does
seem
the two of this
oxide.
The
fifth
relatively
small
amounts
of a water
soluble
preparation
the response
to massive
vitamin
K therapy
is an additional
between
the “congenital”
and the “acquired”
form
of
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
LEY,
READER,
hypoprothrombinemia
is not
SORENSON
known.
AND
Of
the
753
OVERMAN
“congenital”
cases,
of Hagen
and Watson,”
day
period,
received
Heindl,
et al.,’2 Lewis
who n-as given 800 mg. of vitamin
anything
approaching
the d!osage
and Bennett.’#{176} and those
presented
The
whereas
2 patients
indicates
that
vitamin
K,
water
soluble
vitamin
K preparation
not.
data
the
on these
synthetic
Lewis
these
should
the
and
a case of
the patient
hours
before
action
appears
then
received
next.
forty-eight.
effect.
more
intravenously
1 ,000
mg.
hours.
The
water
have
alone.
not
known
effects.
related
She
n-as
given
over
a period
and
within
how
five
these
anticoagulant
K activit.y,
toward
coagulants
by
and
anticoagulants24
vitamin
K
oxid!e
and
infusion
without
dose
K,
at. this
2 patients
vitamin
definite
inactivate
K1 oxide
conclusions
the
might
can
to
the
short-
both
agents
the difference
intermittent.
doses
of
hours.
response
She
over
the
oxide
produced
a definite
time
prodluced!
a normal
effectiveness
of
derivatives
compounds
the
exert
systems
recognized.
by
vitamin
cannot
their
K,
characteristic
water
soluble
the
from
and
It.
the
is
l)iologic
certain
compounc!s
structurally
The structural
similarities
of the
lend support
to the
through
a common
explain
be made
oxide
explained.
be
possessing
vitamin
vitamin
K activity
suggestion
system.
that
Since
oxide
was effective
in restoring
normal
prothrombin
activity
presence
of a vitamin
K inhibitor
should
not be exeludled!.
these
that
or
of seventy-tn-o
derivatives23
t.o substances
action
of compounds
with
act.
response
In Case
1 it
of menadlione
(luring
large
of vitamin
a second
of enzyme
is n’ell
4-hydroxycoumarin
the antagonistic
mg.
case
days.
essential
and
these
K,
effect
thousand
therapeutic
been
due to either
In Case 2, however,
evident.
of menadione
The inactivation
to their
substrates
vitamin
w-ithout
difference
between
the
soluble
methylnaphthoquinone
,
in
the
oxide
was effective
(menadione)
was
hypoprothrombinemia.
his largest
doses
the
hours,
time
difference
time
could
K1 oxide
One
in forty-eight
prot.hromhin
this
idiopathic
n-as given
he received
of the prothromhin
than
to the vitamin
menadione
.-
in
that
thirty-six
ening
rather
in
Bennett’#{176} observed
substances
be noted
only
K1 oxide over a three
used! in the cases
of
in this report.
vitamin
dhfference
in
the available
The
antiK1
in these
cases the
possibility
that
K more
their
these
vitamin
rapidly
actions.
than
the
However,
no
d!ata.
SUMMARY
Two
cases
there
case
In
each
t.hat
the
of
was
there
hypoprothrombinemia
a marked
were
of unknon-n
hemorrhagic
ad!ditional
prothrombin
diathesis
findings
d!eficiency
n-as
(clinical
only
or
one
are
cause
which,
In
presented.
in Case
1, led
necropsy)
which
manifestation
of
each
to death.
suggested
a generalized
disease.
The
reported
pertinent
cases
literature
of
is reviewed
“i(liopathic
and!
a classification
hypoprothrombincmia”
of
into
“acquired”
types
is offered.
Both
of our cases
fall into the
The treatment
of the condition
is d!iscussed!
and it is pointed!
K1
oxide
apparent
difference
in
failure
large
(loses
of
in response
/
large
restored
the
doses
of water
is suggested.
prothrombin
soluble
time
menadione.
the
previously
“congenital”
and!
group.
“acquired”
out
to
that
normal
A rationale
vitamin
after
for
the
this
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
754
IDIOPATHIC
HYPOPROTHROMBINEMIA
CONCLUSIONS
I
Idiopathic
.
hypoprothrombinemia
The acdluired
type
pathologic
states.
2.
Stood!
3.
In
the
presence
administration
of
of the more
4. While
time
short
may
may
of
be
a manifestation
a prothrombin
deficiency
soluble
n’ater
be congenital
only
which
methylnaphthoquinone
potent
vitamin
K,
large doses of vitamin
to normal
in 2 cases
times
was observed.
or acquired.
of certain
no
is
to produce
an
under-
resistant
the
to
compounds,
oxide
should
be used.
K, oxide produced
a return
tendency
poorly
large
of the
overswing
doses
prothrombin
to abnormally
REFERENCES
I
RH0AD5,
J. E.
unrecorded
2
AND
T.,
FJTZ-HUGH,
condition.
Am.
A. S. : Idiopathic
(h0RnANO,
: Idiopathic
JR.
hypoprothrombincmia-an
662-670,
J. M. Sc. 202:
hypoprothrombinemia.
1941.
Am.
J.
apparently
Clin.
Path.
13:
285-287,
1943.
3
F. D.
MURPHY,
77-83,
207:
4 n)E
-
6
1IA1JSER,
1:
8
: Idiopathic
G. :
BolcHIL,
AND
1088-1092,
F.
165:
J. K.
CLARK,
hypoprothrombincmia.
idliopatica.
: Famili#{228}n-e,
142-148,
V.
T.
case.
Am.
J.
Hipoprotrombinensia
Semana
AND
H.
QUASTLER,
M.
Sc.
379-386,
J. H.
A and
210:
P.
& Clin.
AND
S.
I.
Sc.
med.
csp#{227}ns. 1: 476-477,
1945.
Ann
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1951 6: 740-755
Idiopathic Hypoprothrombinemia Associated with Hemorrhagic Diathesis,
and the Effect of Vitamin K
ALLYN B. LEY, GEORGE G. READER, C. W. SORENSON and RALPH S. OVERMAN
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