From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
Thrombocytopenia
By
T. C.
P.
BITHELL,
I
N CONTRAST
herited
disorders
ports
of hereditary
porting
play
to
laboratory
This
report
have
result
Those
a family
been
as a definite
members
with
a hemorrhagic
thrombocytopenia
WINTROBE
convincing
and
of eight
afflicted
of mild
more
features
emerges
M. M.
AND
of red cells and white
cells,
into be rare.
Among
the few
resome
lack
essential
history
or sup-
present
clinical
Autosomal
CARTWRIGHT
disorders
appear
which
cf
syndrome7
concerns
generations
to be the
the hereditary
of the platelets
thrombocytopenia,1’4
variety
Aldrich
G. E.
DmI5HEINI,
data.
a remarkable
so-called
Inherited
as an
Dominant
Trait
evidence
genetic
patterns.
clinical
and
of
genetic
a kindred
in
diathesis
inherited
as an
dis-
Only
the
entity.
which
which
autosomal
four
appears
dominant
trait.
FAMILY
The
marized
occurrence
in
of
pedigree
bleeding
form
in
symptoms
figure
1. Our
REPORT
and
first
thronibocytopenia
contact
when
V-31 was referred
to this center
for evaluation
responded
to splenecton#{236}y. In 1962, V-29 was referred
ity,
and
consists
when
of
she
eight
was
members
found
to
of
be
this
evaluation
a study
IV
this
kindred
was
family
of thronlbocytopenia
for
thrombocytopenic,
generations
in
with
and
V,
of
of
the
revealed
is
made
which
abnormal
entire
sum-
in 1958,
had not
bruisabil-
family,
which
thrombocytopenia
in
her
father
(IV-23)
and in two of her remaining
four siblings
(V-28,
V-33).
Of the five family
members
found
to be thronibocytopenic
(IV-23,
V-28,
V-29,
V-31,
V-33),
the date when
abnormal
bleeding
began
was apparent
in only one instance
(V-29);
here it was first noted
at age 14. The others
recalled
symptoms
beginning
in “childhood.”
These
symptoms
included
increased
bruisability
in all five, frequent
spontaneous
epistaxes
in two of five, and prolonged
bleeding
and “slow”
wound
healing
in two of five. In V-28,
prolonged
bleeding,
sufficient
to require
resuturing,
followed
a tonsillectomy,
but
circumcisions
at birth
in IV-23,
V-28 and V-31,
and an appendectomy
and a tooth
extraction
in IV-23,
were
tolerated
without
complications.
There
is no other history
of surgical
procedures,
and the only potentially
serious
bleeding
manifestations
related
were two selflimited
episodes
of hematuria
in V-28,
which
were presumed
to be the result
of a flank
contusion.
There
is no history
of petechial
skin lesions,
or of swollen,
discolored,
or painful joints.
No one in the family
has ever required
hospitalization
or received
blood
transfusions
for hemorrhage,
and the bleeding
symptoms
have caused
concern
sufficient
to result in medical
consultation
in only one instance
(V-29).
IV-24
and V-29
related
a history
of mild
eczema,
and V-28
and V-31 have
suffered
from recurrent
generalized
urticaria
following
contact
with foliage
and penicillin
administration.
The medical
history
of the family
was otherwise
essentially
negative.
None
of the
heretofore
described
causes
of thrombocytopenia15
has
affected
the
thrombocytopenic
members
of this family
in common,
except
for epidemic
parotitis
or mumps.
However,
this
infection
developed
after
definite
symptoms
of abnormal
bleeding
had
been
noted
by
From the Department
of Medicine,
University
Utah.
This investigation
was supported
by a research
ing grant (AM-5098)
from the National
Institute
tional Institutes
of Health,
Bethesda,
Md.
Submitted
Apr. 7, 1964; accepted
for publication
of Utah
College
of Medicine,
Salt
Lake
City,
grant
(AM-04489)
and
and
of Arthritis
May
22,
Metabolic
a graduate
Diseases,
trainNa-
1964.
231
BLOOD,
VOL.
25,
No.
2 (FEBRUARY),
1965
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232
BITHELL,
DIDISHEIM,
CARTWRIGHT
AND
WINTROBE
MALE
0
FEMALE
0
SEX UNKNOWN
K’
MISCARRIAGE
#{149}
DECEASED
t
IDENTICAL
TWINS
NON-IDENTICAL
CHILDLESS
Fig.
V-28
and
V-31.
pedigree
I
thrombocytopenia
and
abnormal
bleeding
symptoms.
The
generations
in this
pedigree
are numbered
with
roman
numerals
from I to VI and members
of sibships
are illustrated
from left to right in order
of
age. The numbers
which
designate
the family
studied
here are illustrated
in boldfaced
type. The symbols
for all spouses
of the descendants
of 11-2 are omitted.
The
family
lines of the paternal
side are solid
(
) whereas
those
of the maternal
side are interrupted
(
). Numbered
individuals
designate
those
in whom
adequate
history
has been obtained,
whereas
in those not numbered,
the information
was considered
to be inadequate.
The symbols
of members
without
a significant
history
of abnormal
bleeding
symptoms
are uncolored,
whereas
those judged
to have
a significant
history
of abnormal
bleeding
symptoms
are half-colored.
Those
with
normal
platelet
counts
are cross-hatched,
whereas
those
with
thrombocytopenia
(see
also
text
and table 1) are solid colored.
IV-23,
1.-Condensed
TWINS
MARRIAGE
A complete
and revealed
none of the
drome or the amegakaryocytic
of
physical
examination
of all eight
stigmata
which are frequently
associated
or hypoplastic
variety of congenital
FAMILY
members
was
negative,
with the Fanconi
thrombocytopenia.15
syn-
HISTORY
In.formation
concerning
other members
of the kindred
was obtained
by correspondence
and from unusually
complete
and accurate
family
records.
Platelet
counts,
blood
smears,
and more detailed
histories
were obtained,
when possible,
through
the courtesy
of local
physicians.
The results
of tests performed
in such
cooperating
laboratories
are included
within the text.
-
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
INHERITED
233
THROMBOCYTOPENIA
Both
in this
parents
originated
in
emigrated
from
Stemmen,
family
are
near
Rinteln
Niedermoellrich,
of German
extraction.
( Niedersachsen
Kreis
Melsungen
The
province
maternal
) , whereas
side of the family
the paternal
side
( Nordrhein-Westfalen
province).
These
areas are separated
by approximately
ited in the five generations
of the
There is no history
of abnormal
100 miles.
No history
of consanguinity
could
be elicfamily
that have lived in the United
States.
bleeding
among
members
of the maternal
side of the
on two of the four siblings
of IV-24
( W-25,
P1-26)
were normal.
of abnormal
bleeding
in four generations
of the paternal
side of
family.
Platelet
counts
In contrast,
the history
the family is impressive.
Generation
The
back
II
history
as
11-2.
of abnormal
He
suffered
bleeding
from
on the
a relatively
paternal
severe
side
of the
hemorrhagic
family
diathesis,
can
he traced
judging
as far
from
in-
cidents
related
in family
records
and confirmed
by his surviving
children.
These
included
frequent
and severe
spontaneous
epistaxes
which
lasted
for several
days
and frequently
required
hospitalization.
Large
bruises
and alarming
hemorrhage
from trivial
injuries
cornpletely
incapacitated
him for manual
labor
and a diagnosis
of hemophilia
was made
by
one physician.
He nevertheless
lived to age 79, when he died of apoplexy.
His sister (11-7)
and her descendants
(111-14,
V-49)
apparently
were also afflicted with some form of abnormal bleeding,
but little definite
history
is available
concerning
this branch
of the family.
Generation
III
Among
the 12 children
of 11-2 the platelet
counts
were normal
and the bleeding
histories
were negative
in two (111-7, 111-12),
and two
(111-8, 111-il)
were
thrombocytopenic
but
had otherwise
normal
blood counts.
111-8 (platelet
count
50,000/mm3
)has suffered
from
increased
bruisability,
prolonged
epistaxes,
and hemorrhages
following
dental
surgery
since
childhood
which
have,
on occasion,
required
hospitalization
and blood
transfusions.
IH-1 1
(platelet
count
72,000/mm3)
has similar
but somewhat
less severe
symptoms.
Generation
IV
Of the 41 grandchildren
of 11-2, the platelet
counts
were normal
in 18, who related
no
symptoms
of abnormal
bleeding.
Four
were thrombocytopenic
(IV-1,
IV-3,
IV-9,
IV-2.3).
IV-9 has chronic
thrombocytopenia
(platelet
count
25,000/mm3),
first discovered
in adult
life, which
has not responded
to either
cortico-steroid
hormone
therapy
or splenectomy.
Except
for the presence
of moderate
hypersegmentation
of the neutrophils
and HowellJolly bodies
in the blood
smear,
his blood
counts
are normal.
Two
others
(IV-1,
P1-3)
have
low platelet
counts
(77,000/mm3
and 61,000/mm3,
respectively)
but no symptoms
of
abnormal
bleeding.
Of the remaining
was related
by P1-5, and seven
No information
is available
concerning
ability
19 grandchildren,
a history
of increased
bruismembers
have no symptoms
of abnormal
bleeding.
the remaining
11 members,
six of whom
are de-
ceased.
Generation
V
Among
the 64 great-grandchildren
cytopenia
and one other
(V-21)
has
mm3)
but no symptoms
of abnormal
members.
Eighteen
others
have
no
available
Generation
concerning
the
remaining
of 11-2, four (the children
of IV-23)
have
thromboequivocal
thrombocytopenia
(platelet
count
109,000/
bleeding.
The
platelet
counts
were
normal
in 23
symptoms
of abnormal
bleeding.
No information
is
18.
VI
To date, 25 children
mal in two members
seven
others,
and no
have been born in this generation.
The platelet
(VI-8,
VI-9).
No symptoms
of abnormal
bleeding
information
is available
regarding
the remaining
counts
were
16.
were
related
norby
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
234
BITHELL,
DIDISHEIM,
following
studied
eosinophil
counts,
counts
were
by
the
Clot
and
observed
range
of
of
by
in
mented
cells
evidenced
( IV-23,
for
their
cytosis
of the
The
platelets
#{149}1921
family
were
phase
contrast
members
and
somes
of IV-23
Utilizing
carried
with
blood
clot
platelets,22
five
siliconed
serum
blood
red
smear,
serologic
test
of
globulin,
serum
in
stained
segneutro-
the
glass
red
cell
complete
results
for
count,
urinalysis,
syphilis
and
(V.D.R.L.),
alkaline
the
in
the
Eosinophil
had
signifipoikilo-
members
of
and
obtained
the
under
from
the
affected
and
appearance
preparations
were
other-
no
platelets
specific
were
demonstrated
isologous
or
and
following
the
Arimura.18
but
unaffected
The
coagulation
clotting
test
time.
time,
chromo-
quantitative
of these
for
total
phosphatases,
occult
were
the
cell
blood
protein
fasting
levels
of
VIII
(antitime,
and
normal.
additional
red
serum
of
Factor
thrombin
tests
were
whole
normal
isologous
studies
on the
assay
globulin),
time,
plasma
following
studies
qualitative
utilizing
Supplementary
hemoglobin,
stool
found
bodies.
in V-31
normal
tube
included
The
significant
appearance.
generation
prothrombin
time.
the
IV-23
thrombocytopenic
and
on
of
demonstrated
were
Minnich,
in number
cells
been
normal.
marrow
the
white
members
occasions.
in number
bone
Factor
V (accelerator
plasma
recalcification
acid
inwas
normally
whose
preparations
aspirates
either
obtained
had
several
thrombocytopenic
),4
were
for
four
size
statistically
of V-31
normal
results:
clotting
cells,
the
counts
by
500
of Howell-Jolly
and
The
members
values
smear
presence
methods,13”7
normal
factor),
tube
were
of Harrington,
normal
I (fibrinogen
Normal
packed
the
lysis,
thromboplastin
and the one-Stage
hemophilic
V-32,
counting
family
removed
at surgery
No agglutinins
for
thrombocytopenic
Factor
and
for
eosinophilia
blood
Marrow
technic
were
by
on
the
the
platelets.
standard
out
Lobe
normal
family,
was
are
smears
of
eosinophilia
megakaryocytes
in the
the
sites.
thiombocytopenic
( V-31 )
normal
wise normal.
The spleen
histologic
abnormalities.
by
five
unaffected
microscope.
surrounding
members
of
and
both
revealed
demonstrable
the
samples.
test
recorded’7
coded
were
tabulated
separate
times
except
made
the
Significant
morphologically
and
few
.05),
cells
in
values
separate
of
1. Platelet
tourniquet
neutrophils
members,
member
=
red
on
different
evidenced
members
(p
counts
The
of
were
of
V-33)
.05)
in unaffected
with
counts
V-29,
(p
basophilia
four
members
thrombocytopenic
counts
cant
from
Four
V-28,
age
The
three
table
Cronkite,1#{176} and
smear.
bleeding
at
in
of the
studies,
hypersegmentation.
cell
smears.
remaining
The
in normal
slight
white
different
family
independent
thrombocytopenic
Differential
four
made
found
found
and
quantitatively.15
Hypersegmentation
were
are
blood
determinations
were
all
peripheral
several
WINTROBE
the eight
members
counts,
hemostatic
of Brecher
method.’7
separate
observers.
present
phils
of
on
counts
method
determined
neutrophils
500
dependent
lobe
the
a standard
three
were
obtained
of the platelet
of the
was
out
mean
by
examination
retraction
carried
data
results
neutrophil
performed
confirmed
are
laboratory
here.
The
AND
DATA
LABORATORY
The
family
CARTWRIGHT
tests:
indices,
volume
(guaiac
and
blood
of
peripheral
method),
albumin
sugar,
and
blood
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
INHERITED
235
THROMBOCYTOPENIA
Table
1.-Pertinent
Platelets
(per mm3
Patient
(Pedigree
Number)
Laboratory
x 10)
No. of
Counts
Range
IV-23
26-74
3
IV-24
200-250
3
V-28
V-29
32-40
V-30
300-320
47-58
61
265-318
52-76
Normal
Reported
Bleeding
Time
(Minutes)
0
>15
5
0
0
>15
4
0
0
>15
3
58
0
1041
15.8
4171
10.3
4201
20
3
55
0
3
36
1-4
4451
2.2
6
1+
Eosinophils
(per mm’
x 10’)
10.4
1+
0
Family
Percentage
of
Neutrophils
with More than
4 Lobes
2.4
1381
8.9
216
6
>15
5.9
159
11.7
936
Range
(95%
Confidence
0-4001
Limits)
140-440
#{176}Clotretraction
serum
expressed
flncludes
counts
15-adulthood.
SAges
8-14.
urea
40-94
is expressed
in 4 hours.
SAges
as
obtained
nitrogen,
over
serum
0-1+
a percentage
a period
bilirubin,
of
of
fecal
serum
ova
globulins
and
plete
blood
and
the
major
for
parasites.
phenotype
or
to
groups
of
V-28-33
of
theoretical
maximum
( random
Coombs
test
common
of
foods,
stool
chest
and
the
apparent
indirect),
examination
with
for
A
between
and
electro-
skeleton.
correlation
compatible
specimen),
and
cells,
paper
immuno-electrophoresis
thrombocytopenia,
were
0-600
volume
stool
(direct
erythematosus
antibodies,
of
no
absence
0-3.25
urobilinogen
roentgenograms
revealed
presence
blood
antibodies
and
the
1-11
4 years.
urine
urobilinogen
(2-4
p.m.
excretion),
reticulocyte
count,
preparation
for lupus
phoresis
of serum
proteins,
nuclear
binding
of
on the
Tourniquet
Teat
0
41
V-33
Clot
Retraction
(Per cent*)
55
22-50
V-32
Data
in
any
all
comfactor
instances
the
legitimacy.
DIscussIoN
of
the
humans
Many
are
illustrated
reports
have,
history
of
fruitful
in those
in
and
of necessity,
one
of
which
on
may
may
generation
affect
more
thrombocytopenia,
a result,
when
it is not
critically
common
or
hypoplastic
“auto-immune”
or
laboratory
data.
of
and
etiologic
or more
that
examined,
symptomatic
as
history
Furthermore,
a sibship,
surprising
death
exist
family
of diseases
are
hemostatic
defect,2
or one of the congenital
varieties
In the present
family,
the bone
marrow
findings
are
more
secondary
of the
another
penia.3
amegakaryocytic
of
value
with
The
presence
member
in
can
a
is most
result
however,
variety
by
which
patible
the
the
one
in
Most
supplemented
invariably
the
of a large
than
As
i.e.,
supplied
result
disorders
approach
family,
limits
genetic
family
an
sublethal,
present
externally
of
thrombocytopenia.
of one
kindred,
which
be the
of a kindred.
hereditary
the
study
inherited
a study
are
in
the
on
their
condition,
a reliance
which
on
in
disorder
asymptomatic
imposes
relied
varieties
The
in
literature
symptoms
thrombocytopenia
factors
encountered
in the
bleeding
childhood.
virtually
problems
some
more
than
reports
com-
thrombocytopenia,’
of thrombocytoinconsistent
with
variety
of
congenital
thrombocytopenia.
variety
of
congenital
thrombocytopenia,
a
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
236
BITHELL,
which
occurs
in infants
purpura,
oif
cannot
born
the
and
physical
the
negative
of mothers
explain
fected,
whereas
thrombocytopenia
the
mother
or purpura.
examination
of thrombocytopenia,
incomplete
form
of the
Conversely,
clinically
chronic
volunteer
have
been
carefully
laboratory
and
of
several
present
probability;
males,
mented
and
two
counts
were
The
further
probable
two
instances
in
the
deceased,
11-2,
the
trait
in
No counts
deceased.
The
small
but
of
had
cytopenic
the
parents
numbers
involved
in
number
parent
(11
X2
=
is
living
and
the
six are
females.
both
of
IV-9
study
render
would
be
abnormal
and
all
who
are
treatment
to be
or on
of
bleeding.
V-21,
statistical
(23
and
Although
corresponds
with
a known
> .9)
is
the
propositus
expected
of inheritance,
on sibships
It
In
parents
apparent
IV-3,
docuplatelet
parent.
history
a
af-
whcm
responsible.
affected
this
=
support
three
justified.
on
an
who
p
basis
with
for
males
obtained
member
The
presence
on the
individuals
those
and
.05,
families
available
to
family
exhibits
is
Ill-il
thrombocytopenic
only
inheritance
had
of
is negligible.
appears
were
mode
only
members,
excluded
are
of IV-1,
of persons
cases
include
ITP
involved
impressive
on
a documented
five
of
and
an
be
the
is
counts
111-8
of
kindred
reported
members
cytopenic,
assuming
a dominant
that
observed,
whether
computed
contain
resemble
individuals
frequently
Few
of these
families
including
mode
available
the
or an
which
pur-
thrombocytopenia.23’2527
of ITP
could
explain
the
Of
trait
platelet
father
exclude
anomaly
the
physicians,
a dominant
pedigree,
this
The
autosomal
which
the
this
kindred,
thrombocytopenic
are
tenuous,
an
that
children,
the
by outside
that
family
indefinable,
females.
in
supplied
conclusion
this
can
although
affected
thrombocytopenia
is af-
history
of
members
thrombocytopenia
thrombocytopenic
reviews
for
kindred
this,
Sufficient
information
concerning
simple
single-factor
genetic
hypothesis.
fected
a history
father
together
Heggelin
disorder
wherein
affected
of abnormal
bleeding.15’23’24
in the
statistical
the
studies,
as the
of hereditary
with
idiopathic
members
studied,
of thrombocytopenia
or
since
normal
and gives
no
expectancy
of affected
life
whose
history
suggests
a hereditary
basis
possibility
that the coincidental
occurrence
of its
WINTROBE
syndrome.15
the
ITP,
a common
a family
history
family,
as well
that cases
confused
Individually,
.
AND
thrombocytopenia
this
and
Fanconi
it is probable
mild have
been
( ITP)
pura
in
is hemostatically
The normal
form
CARTWRICHT
with
disorder
a secondary
are
DIDISHEIM,
thromboclosely
thrombo-
sibships
members,
X2
to
which
.34,
=
p
=
The
authors
thesis
in the
the
following
presently
the
known
occurrence
a pattern
penia
that
of
that
or
the
base
reported
evidence:
thrombocytopenia
preliminary
family
(a)
causes
conclusion
is the result
the
exclusion
of symptomatic
of thrombocytopenia
excludes
congenital
numbers
their
the
or
coincidental
sex
are
of affected
predictable
secondary
occurrence
as
an
individuals
by
that
the
inherited
of other
in several
thrombocytopenia
and
of
a simple
hemorrhagic
dia-
thrombocytopenia
hemostatic
defects
thrombocytopenia;
members
of three
of idiopathic
explanation;
and the
genetic
and
pattern
hypothesis.
on
or
(b)
generations,
thrombocyto(c)
the fact
of occurrence
Table
2
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
INHERITED
237
THROMBOCYTOPENIA
Table
2.-Summary
of Reports
Hypothesized
Mode of
Inheritance
Author
Severity
Symptoms
Prognosis
A.
Roberts
and
Varieties
Autosomal
of inherited
Megakaryocytes
with
Recessive
early
Numbers
death
decreased
1 case,
and
Schaar’
Sex-linked
Severe;
early
death
Normal
? Sex-linked
Mild;
Normal
life
Findings
normal
expectancy
in
normal
case.
Not
in 2 cases
Aldrich
others7
Ancillary
Inhcritance
Severe;
Smith6
Thrombocytopenia
of
and
in
1
examined
Leukopenia.
Anemia
Allergies.
Eosinophilia
numbers
case.
Not
in I
Eosinophilia
examined
in 6 cases
B. Varieties
Witts’#{176}
Autosomal
with
Mild;
life
Wooley”
Autosomal
Mild;
Autosomal
report
normal
Mild;
Autosomal
examined
None
Normal
None
expectancy
life
Present
J,,herittencc
Not
expectancy
life
Quittner’
Doesinv,it
normal
normal
Not
examined
None
expectancy
Mild; normal
Normal;
life
rounding
expectancy
few
sur-
Eosinophilia
platelets
Hypersegmented
Neutrophils
Quick
and
Hussey’3
Autosomal
Moderate;
ameliorated
Not
examined
Platelets
morphologically
in
adolescence
and
functionally
abnormal
Larrain
and
Etcheverry’4
Autosomal
Mild;
ameliorated
in
adolescerce
Numbers
increased,
but without
sur-
Morphological
abnormalities
rounding
platelets
platelets
in 2 cases
summarizes
reports
sented.
not
Two
included.4’5
At least
two
been
described.
ten
siblings
of
only
one
generation
trait
was
responsible,
the
possibility,
plete
form
both
the
cytopenia.
In
cytopenia,
recurrent
termination
family
died
was
studied.
remote,
Fanconi
has
recessive
recently
The
an
otitis
which
was
bears
mode
reported
of
could
bloody
a recessive
Smith,6
hemorrhage,
that
are
from
an
observed
unaffected
resemblance
to
has
in which
been
four
this
thrombo-
invariably
mothers
syndrome,
confirmed
of seven
with
incom-
thromboby
an
of
inherited
as an
characterized
and
trait
four
compatible
such
the
are
although
fatal
by male
with
allergic
symptoms
and
symptoms
and th eosinophilia,
inheritance
a family
as
disorder,
diarrhea,
inherited
form
and
concluded
explain
is pre-
preliminary
findings
a syndrome
no
of
childhood
underlying
associated
of the allergic
family
Roberts
blood
described
media,
by
authors
ancillary
syndrome,
Aldrich7
described
early
that
evidence
in only
inherited
reported
in
the
and was frequently
With
the exception
sex-linked
Schaar8
thrombocytopenia
thrombocytopenia
comparable
presented
of
sexes
life,
in which
been
the
but
in early
presently
the
1954,
literature
have
In
albeit
of
the
which
varieties
have
children,
philia.
from
reports
of
antedating
eosinothe
wherein
repeatedly.
male
children
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
238
BITHELL,
were
affected
was
with
compatible
in
the
affected
cases
resemble
mild
form
the
this
beyond
the
genetic
itary
thrombocytopenia
Several
been
in the
recessive
is
reported
Two
in contrast
these
the
of
In the
normal,
thromboplastin
affected
evidenced
were
ment
no
of thrombocytopenia
suggests
that
cytopenia
and
abnormal
the
platelets
that
supposed,
mechanisms
but
ing
by
in two
the
hemorrhagic
Little,
and
sheer
pathogenesis
of
which
rendered
in one
of the
even
these
regulates
platelet
more
attractive
chronic
thrombocytopenia
by infusions
of normal
were
interpreted
second
Quick’s
an
interesting
between
to
reand
by
the
reported
in most
the
The
develop-
observation
which
inherited
with
value
thrombo-
morphologically
not
in
with
reported
be
of
one
by
to
incase
Schaar,5
alleviat-
platelet
regard
is a tenable
could
as here-
although
deficiency
recently
etiology
treatment
in
reported
a normal
said
production29
a
the
family
as rare
probably
multiple
neither
splenectom
splenectomy,
restore
be
be
and
a remission
A hereditary
of obscure
plasma.
clot
function.
antedated
of the
can
by
family,
patients
platelet
exist
family,
disorders.
morphologic
Hussey,’3
the
consumption
of
of
member
failed
course,
striking
produced
latter
speculation,
cases
may
be
Splenectomy
symptoms,
beyond
substance
is
and
members
Quit-
differ
at least
three
few exceptions,
to
and
disorder.
inheritance.28
that
With
appears
here
clinical
thrombocytopathy
dominant
excep-
family
aforementioned
The
thrombocytopenia
it is probable
are involved.
Wooleyi1
other
of
autosomal
inherited
and
years,
the
the
apparently
may
types
nor cortico-steroid
therapy
herited
thrombocytopenia.
reported
several
connection
various
and
It is apparent
tofore
genetic
by
a nosologic
platelets
the
of the
which
abnormalities
of the
disorder
With
example
benign
function.
resembling
have
observed
bleeding
span.
Quick
and
in prothrombin
observed
clear-cut
diathesis
evidenced
by
platelet
although
abnormalities
the
individuals
family
studied
but
abnormalities
generation
morphologic
and
sublethal.
trait
Witts,1#{176} Wooley,”
resembling
mechanism
authors
as indicating
deficient
by Larrain
and
Etcheverry,14
respects,
by
published
although
genetic
platelets
fourth
to be
neutrophils,
reported
the
howof hered-
a dominant
life
a
who
exceptions,
a mild
a normal
represent
varieties
hemorrhagic
hypersegmented
those
reports,”’4
to
the
the
these
as
evidenced
with
and
closely
severe
families
they
explanation,
inherited
noted
Schaar’s
syndrome
recessive
obvious
to the
represents
additional
abnormalities.
traction
was
without
was
Aldrich
With
the
inheritance
course,
that
the
described.9
thrombocytopenia
The
clinical
with
WINTROBE
eosinophilia
it is possible
for
AND
birth.
and
benign
and
been
compatible
hence
their
responsible
varieties,
respect
that
have
eosinophilia
and
trait,
patients
appears,
of
resembles
tner,’2
in
Other
apparently
of the
with
syndrome,
and
which
lion
Aldrich
examples
described,
for
disorder.
abnormality
since
recessive
Except
childhood
ever,
CARTWRIGHT
thrombocytopenia
a sex-linked
members.
of
survived
moderate
with
DIDI5HEIM,
count.
the
of
etiology
a humoral
hypothesis,
which
case3#{176}in
predictably
which
alleviated
CoNcLusIoNs
This
kindred
report
afflicted
summarizes
with
information
a mild
hemorrhagic
obtained
diathesis.
on
four
Studies
generations
carried
out
of
a
on
a
From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
INHERITED
239
THROMBOCYTOPENIA
family
of eight
members
members
and
demonstrated
three
generations.
somal
dominant
only
The
platelet
counts
mild
thrombocytopenia
reporto
Studios
in un
effectuate
penia
un
es un
parentage
gruppo
in
solmente
IN
summario
to be
additional
members
inherited
as an
of
auto-
de
de
octo
subjectos
dece-un
un
information
leve
membros
additional
membros
es transmittite
INTERLINGUA
del
affligite
familial
in cinquanta-un
thrombocytopenia
fifty-one
eleven
trait.
Le presente
de
on
in
appears
SUMMARIO
erationes
obtained
thrombocytopenia
de
geneticamente
forma
colligite
de
un
generationes.
como
un
gen-
hemorrhagic.
e numerationes
revelava
tres
in quatro
diathese
del
leve
plachettas
thrombocytoIi
pare
dominante
que
le
character
autosomaL
ACKNOWLEDGMENTS
The authors
wish to express
their
thanks
to Dr. T. L. Sutton,
Stockton,
California,
for
referring
this family
to us, to the numerous
physicians
who provided
additional
history
and laboratory
data,
and to the members
of the reported
family
for their cooperation
in
accumulating
the information
contained
in this report.
The authors
are indebted
to Sister
MAnn
Josephine,
C.S.C.,
who performed
the chromosome
studies,
and to Dr. D. C. Heiner,
for the serum
immunoelectrophoreses.
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From www.bloodjournal.org by guest on June 16, 2017. For personal use only.
1965 25: 231-240
Thrombocytopenia Inherited as an Autosomal Dominant Trait
T. C. BITHELL, P. DIDISHEIM, G. E. CARTWRIGHT and M. M. WINTROBE
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