For personal use only. on February 3, 2015. by guest www

From www.bloodjournal.org by guest on February 11, 2015. For personal use only.
EFFECT
THE
OF
ROCYTE
CELLS
RED
STASIS
OF
FRAGILITY,
BLOOD
WITH
AND
IN
VARICOSE
VEINS
ACCOMPANYING
OTHER
BLOOD
ON
STUDIES
ELEMENTS
ERYTH-
COMPARING
WITH
CUB1TAL
VEIN
BLOOD
BJSTAcYR.
METTIER,M.D.,JOHNC.
F.
ALICE
I
T HAS been demonstrated
by Fahraeus’4
tendency
to bcccme
spheroidal
in shape
perature.
G#{228}nsslen,5 Haden6
and Castle
and
red cells are
Haden
found
lutions
tonic,
and
more
that
become
and that
fragility
susceptible
normal
red
of the
stated
that
temperature.
one-half
hours
During
evidence
fragility.
blood
of stasis
stasis
volume
red
was
hemolysis
suspended
to
that
under
some
conditicns,
Waller12
and Cormick’3
fcuEd
blood
fcllcwing
tourni4uet
removed
frCm
the cubital
capillary
blood
into the
and
Castle8
before
and
the
first
appeared
temperature
develo#{231}ment
red blood
cells have
a
in vitro
at body
ternshown
that spheroidal
than
are
in graded
is increased
by stasis
found
that
between
hemolysis
at body
the
AND
normal
corpuscles.
hypotonic
salt so-
as the solution
becomes
more
between
the volume
thickness
Ham
necessary
Spontaneous
of blood
due
cells.
red cell fragility
These
investigators
fragility
appeared.
hours of stasis.
cell
to osmotic
cells when
that
normal
after standing
Daland7
have
progressively
more
globular
there
is a direct
relationship
further
body
M.D.,
WEAVER,
BA.
MCBRIDE,
there
of
spheroidal
Tsai,
Lee
and
hypoindex
Wu#{176}
have
of the blood
in vitro
at
one-half
and two and
manifestation
of increased
after
approximately
twelve
is also
an increase
in packed
cells.8’
‘#{176}“
There
is
also
in vivo
stasis
produces
increased
red cell
an increase
in red cell fragility
in capillary
stasis,
but Wailer
found no increased
vein under
conditions
of stasis
except
veins.
fragility
after
in blood
expressing
There
is evidence
that concentration
and stasis of red blood
cells occur normally
in the spleen.’1’6
Red cells obtained
from the spienic
vein were found
to be more
fragile
when
suspended
in hypotonic
salt solutions
than
red cells from blood
in
other
veins.8’
9 As further
proof
that in vivo stasis
may cause red cells to become
more fragile,
Tsai and co-workers9
found
that osmotic
fragility
ofred
cells removed
from
both
the
splenic
and
renal
veins
increased
produced
by occlusion
of the veins and arteries
Ham and Castle1’
‘#{176}
have attached
great
on red cells and consider
this factor
to be the
the anemias
due to hemolysis.
They
believe
probably
the mechanism
producing
increased
anemias
with
increased
might
secondarily
account
increased
shown
the
red
the Divisicn
of
stasis
Frcm
that
red cell fragility,
for some
red cell
cells
Medicine
usually
of
and
hemolytic
fragility.
progressively
that
blood
also,
that
anemias
A number
become
less
the University
fragile
of California
1033
following
stasis
of the spleen
and kidney.
importance
to the effects
of stasis
common
denominator
in many
of
erythrostasis
destruction
in the spleen
in the hemolytic
an unusual
degree
in which
there
of investigators9
to hypotonic
Medical
School,
of erythrois normal
1924
salt
San
is
or
have
solutions
Francisco,
Cal.
From www.bloodjournal.org by guest on February 11, 2015. For personal use only.
1034
STASIS
following
as being
OF
BLOOD
splenectomy.
Ham
due to the removal
AND
ERYTHROCYTE
FRAGILITY
and Castle interprett
the beneficial
effect ofsplenectomy
of the organ
in which
a large degree
of red cell stasis
( and thus increased
fragility)
splenomegaly
on the basis
respect
to erythrostasis.
occurs.
They explain
of a probable
increase
certain
anemias
in normal
splenic
In an attempt
to evaluate
further
the effect of in vivo stasis
anism
for increasing
red cell fragility,
the present
investigation
to measure
out any
of stasis
ment
the
of
the
leg
osmotic
fragility
known
hemolytic
in varicose
veins
blood
with
possibility
definitely
‘
again
ripheral
is very
veins
cells
sluggish.
as having
of a given
blood
‘coming
up each
McPheeters
blood
veins
Rice26
cell remaining
time perhaps
studied
Ochsner
a circulation
in
patients
2.0
the
and
of its
Mahorner25
own.
with-
the
the
degree
move-
visualize
They
consider
in the venous
system
of the
to the opening
of the saphenous
one of the unhappy
ones
superficial
venous
system.”
and
from
with
with
as a possible
mechwas undertaken
tendency
or other
blood
dyscrasia.
Although
is not known
it seems well established
that
in varicosities
varicose
becomes
in the
it
of red
associated
function
to fall
direction
through
the
of blood
flow
the
leg inwhere
opened
sluices
pe-
in leg
varicosities
and
discussed
in detail
the movement
of lipiodol
injected
into the varicosities
of
two
patients
with
a positive
Trendelenburg
test. One subject
was recumbent
and
the other
sitting
with
legs horizontal.
In both cases the injected
lipiodol
remained
stationary
lowing
never
until
the patient
which
the lipiodol
moved
centrally.
tensed
the abdominal
muscles
or moved
the
was seen to move distally.
In their
experience
However,
Schmier27
and
Heller28
observed
feet,
the
that
foldye
injected
radio
opaque
material
moved
in a central
direction.
Heller
determined
the specific
gravity
of blood
removed
from
the varicose
vein under
observation
and then injcctcd
radio
opaque
dye of the same specific
gravity.
He found
in patients
having
varicose
veins
and competent
valves
that
the circulation
was directed
centrally
but at a slower
rate than in the normal
control.
In patients
with incompetent
the flow was nearly
stationary
but after
the patient
remained
standing
time a very slow upward
flow developed.
Coughing
or straining
rapidly
the flow and forced
the opaque
substance
distally.
He also noted
that
patient
first
the varicose
stands
vein.
blood
stagnates
stasis
does
after
While
in the
being in a supine
position
there
is no definite
proof
varicose
vein
for
hours
there
that
is a surge of blood
down
a significant
quantity
of
is evident
it
valves
for some
reversed
when
the
that
abnormal
erythro-
occur.
MirruoD
The
patients
least
fifteen
and
used
in this
of California
University
minutes.
immediately
study
Medical
Blood
afterward
had
all
Center.
was
then
been
drawn
a similar
previously
Each
sample
patient
from
was
examined
in the
requested
to stand
a tortuous
was
dilated
obtained
Varicose
superficial
the cubital
from
Vein
Clinic
of the
quietly
for
a period
of
vein,
usually
vein
without
on the
the
aid
at
calf,
of a
tourniquet.
The
following
cells.
(a)
count
(Rees
All
The
of the
studies
packed
and
Ecker
laboratory
were
cell
made
volume.
method29).
determinations
on the
()
()
two
specimens
Plasma
were
of blood:
ned blood
Hemoglobin,
protein
(Falling
performed
by
(i)
count,
The
osmotic
white
drop method).
one
of us.
blood
of the red
fragility
count
and
platelet
From www.bloodjournal.org by guest on February 11, 2015. For personal use only.
S.
The
valves
Whi.
were
table
i. One
obvious
of the
not
R.
long
saphenous
tested).
The
patient
blood
.r
METTIER,
(Di)
dyscrasia
veins
clinical
had
VEAVER
were
degree
a varicose
in any
C.
incompetent
and
There
neither
patients
A.
F.
in each
of tortuosity
ulcer.
of the
AND
was
McBR1DE
of the
dilatation
1035
patients
tested
of each
evidence
(Sp.
patient
,
Di.
,
and
is indicated
of congestive
heart
in
failure
nor
studied.
RESULTS
1
.
1-lypotonic
termined
of the
fragilit,y.
on
red
blood
blood
The
resistance
the
cubital
from
cells
from
the
of the
and
varicose
red
blood
varicose
veins
was
not
of
RedCellCount
Arm
Re
4.07
Fr
4.17
McM
!
Varicose
4.2.3
Cell
Volume
----
---
Arm
hypotonic
different
Total
of saline
patients.
from
Protein
Red
---
--
--
\Taricose
solutions
healthy
the
Arm
Cell
Varicose
of red cells
-
Vanicosity
44
42.
42.
44
6.70
7.32.
4.2.8
42.
42.
7.39
7.77
.48-36
6.87
.44-34
.48-34
.48-34
St
4.03
4.33
40.5
40.5
Ke
Sp
5.2.1
5.10
4.36
48
48
6.15
6.66
6.39
6.6
.46-.36
I
.46-32.
.46-36
4.33
47
47
Va
4.72.
5.43
45
44
6.i
5.73
.46-34
.44’.3a
46
6.49
.41-30
.41-32.
#{149}
.50-38
.50-36
.47-32.
Di
4.2.8
4.63
46
Sc
4.40
4.34
44.5
Whe
4,45
4.49
Bro
4.08
Ma
4.89
4.59
47
47
Le
4.37
4.52.
44
44.5
6.32.
6.52.
.48-36
.48-38
41
42.
6.i8
6.49
.41-32.
.44-32.
45
44
Bni
4.2.3
Os
4.60
Win
Mo
4.53
4.88
-
4.2.7
Jo
obtained
Red
creased
the
veins
the
varicose
cell count,
pressure
pected
cubital
in both
range
packed
in
to produce
( a) Our
as
being
results
show
with
million
(b) Surprisingly
*Statistical
Medical
Center.
analyses
cell
a small
the
red cells.*
enough
of
but
cubital
the
.48-38
our
5.63
52.
6.39
7.14
data
107.19
i).
In
and
the
each
protein,
the
vein
varicose
vein
cells
or platelets
increase
blood.
Statistical
is indicative
cell
were
volume
made
red
blood
white
transudation
white
significant
.44-34
.41-32.
++
.41-32.
cell
fragility
fell
within
the
specimens.
hemoglobin,
fluid
.44-34
+++
‘
109.53
patient
cubital
+++
++++
++
++
.44-34
.46-34
5.46
1
.44-32.
.50-38
of the
packed
.46-32.
.46-34
cause
vein
This
6.aa
6.15
serum
fragility,
.41-30
43
should
veins
hemoconcentration
compared
.io8
cell volume,
varicose
increase
in red cells,
red
with
cubital
vein blood.
veins
vein
.41-32.
5.90
891.5
(table
5.87
.48-38
41.5
88a.5
5.94
.48-38
4.55
91.11
.41-32.
6.01
49
88.94
.41-32.
.44-32.
5.94
40.5
49
.44-32.
6.36
47
37
4.55
6.o8
6.18
.46-36
48
++++
6.i
6.i
4.82.
4.43
from
normal
43
47
4.75
4.7’
‘
Wil
2..
4.39
4.72.
Whi
40
43.5
4.2.3
4.75
46
6.42.
of
.44-32.
.44-34
6.87
Degree
Varicose
Arm
4.18
39,5
de-
fragility
fragility
Fragility
_________
--
4.2.0
-
was
The
I
______
Packed
________________
to
otherwise
19
significantly
TABLE
Name
cells
veins
blood.
in red
of varicose
by Dr. John
the
However,
in blood
degree
vein
and
platelet
count.
tissues
which
would
Erb
from
blood
calculations
of a minor
cell count
into
cell
count
show
and
varicose
veins
as compared
from
the mean
varicose
difference
of hemoconcentnation.
blood
C. Talbot
was
only
suggestively
of the University
in-
be cx-
Tickense3#{176} found
in blood
P < o.a,
The
higher
of California
no
From www.bloodjournal.org by guest on February 11, 2015. For personal use only.
6
103
than
STASIS
cubital
blood
in
packed
increase
would
( c) There
(P
the
(P slightly
be expected
veins
was
significance
cubital
volume
that
the
vein
packed
apparent
no
ERYTHROCYTE
If. as result
cell
A more
AND
result,
of stasis,
and
volume
increase
>o.a).
of this
a.a).
would
a suggestive
was
BLOOD
<
cell
somewhat
( d) There
OF
added
would
in total
technic
some
to
red
a certain
increase
serum
accurate
FRAGILITY
out
protein
cell
swelling
amount
of proportion
in varicose
or a larger
series
had
occurred
same
of hemoconcentration
to the
veins
would
red
compared
it
cell
increase.
with
cuhital
be necessary
to establish
cells
varicose
increase.
significant
difference
in hemoglobin,
platelets,
or white
in the
and
samples.
COMMENT
As
mentioned
progression
straining
earlier,
It seems
pressure.
veins
the
of blood
centrally
and coughing
and
does
necessary
not
likely,
an attempt
that
to establish
cell
roughly
the
minutes
after
the
injection.
leg until four minutes
of the arm in a period
slow
and
that
increased
that
Dye
did
not
injection
minutes.
a slow,
through
which
has
fragility
a measurable
in the
ofa
tube.
with
minutes
leveled
veins
Jr.,
marked
after the
off fifteen
of the
dye
dye
In
of blood
J. Hopper,
patient
to reach the
shown
that
arm vein of normal
subjects
appears
in samples
of blood
within
thirty
seconds
and levels off within
three
to four
shown
test
quantity
Doctors
varicose
and failed
It has been
varicose
been
in the
vein blood
until two
increased
and finally
appear
steady
of blood
following
the intra-abdominal
of blood
to
duration
in the cubital
gradually
following
of thirty
movement
we, in collaboration
with
the following
experiment:
injected
into a varicose
vein
No dye appeared
The dye concentration
injection.
indicates
veins with
refluxes
which
increase
comparable
swelling
remains
in the varicose
vein,
and C. J. Mudrick,
performed
Evans
blue dye (Ti8i4)
was
varicosities.
the
stagnation
red
of evidence
in varicose
other
activities
then,
produce
to produce
preponderance
opposite
concentration
injected
in an
taken
from the other
minutes.3’
Obviously
arm
our
experiment
in one patient
and without
controls
has no comparative
value
but it
does indicate
that in this patient
a certain
amount
of stasis
occurred
in the vancosity
for about fifteen minutes.
Further
exp:niments
on this problem
are in progress.
Our
data
stasis
in
fragility
permit
hemolytic
under
erythrostasis
diseases.
We
that
the
regarding
the lack
the importance
of increased
conditions
that
in varicose
of a moderate
are inclined
the hemolytic
agglutinins
as stasis,
no final conclusions
diseases.
However,
and
trauma,
states
of stasis
degree
to agree
does
with
occur
not
the
cell
veins
suggests
that
play a major
part in most hemolytic
viewpoint
of Dameshek
and Miller32
are due to a number
inherited
red
and possibly,
of the factor
of
red cell osmotic
ofdifferent
abnormalities
chemical
and
causes
with
hormonal
occurrence
of hemolysis.
It seems likely
that several
For example,
in the presence
of hemolytic
disease,
such
such
as hemolysins,
supplementary
changes
augmenting
factors
increased
are operating
stasis
and
factors
the
at once.
increased
trauma
to the red cells might
be expected
to produce
some increase
in the degree
of hemolysis.
It also seems likely
that in order for stasis
appreciably
to augment
hemolysis
in any given
hemolytic
syndrome
it is necessary
for stagnation
to occur
over a prolonged
did not appear
period
of time.
until stasis
had
hours
hemolysis
and
that
did
Tsai9 showed
been present
not
begin
until
that increased
red blood
for one-half
hour to two
about
twelve
hours
cell fragility
and one-half
of stasis.
Also
in
From www.bloodjournal.org by guest on February 11, 2015. For personal use only.
5,
our
did
the
R.
J.
METTIER,
C.
WEAVER
AND
A.
experiment
and in Wailer’s’2
a degree
of stasis
not produce
a significant
increase
in fragility
amount
of stasis
present
in congestive
failure
F.
McBRIDE
1037
beyond
that normally
existing
in blood
from veins.
Therefore,
or produced
by increased
blood
viscosity
caused
by the increase
in globulin
in infections
as suggested
would
hardly
seem sufficient
to produce
hemolysis.
It is probable
is the
only
crease
The
in hemolysis,
might
absence
of a greater
vein
blood
cm.
50
organ
in the
is difficult
of water
result
mild
stasis,
of the
Beecher33
colloid
findings
of Erb
platelets,
and
as compared
with
cubital
vein
crease
in red cells in the varicose
red cells were not significantly
SUMMARY
I.
Blood
from
varicose
in order
to determine
would
increase
red
veins
but our
factors
and
pressureof
veins
experiments
are involved
fragility
showed
which
there
in blood
evidence
have not
is no significant
from
varicose
compared
hemoglobin,
in red
with
cubital
packed
cell
in varicose
vein
blood
cell
fragility
as compared
a suggestive,
but not significant,
in the varicose
vein samples.
centration.
4. White
same
values
cells,
platelets
The
and
in varicose
vein
vein
blood
volume,
in the
with
blood
in .o patients
hemoglobin
cell
blood
vein
specimen,
cubital
from
veins.
cells,
inconper
There
cu.
was
volume
and
a mild degree
serum
protein
of hemocon-
were
found
to have
cubital
vein.
determinations
as in blood
veins
de-
white
varicose
from
increase
in packed
evidence
indicates
blood
inthe
CONCLUSIONS
dicating
that
the theory
that
minor
degrees
of intravascular
erythrostasis
tribute
substantially
to some of the hemolytic
anemias
is untenable.
3. There
was a small
but statistically
significant
elevation
in red cells
mm.
veins
whether
or not the degree
of stasis
present
in varicose
cell fragility.
Corollary
studies
consisted
of comparative
terminations
of red cells,
platelets
and serum
proteins.
2_, There
was no increase
and
However,
our finding
of a significant
is at variance
with
their conclusion
that
than
in the cubital
vein.
AND
was
in varicose
filtration
in varicose
Tiefensee3#{176} that
red cell
blood.
vein
higher
blood
in-
we found
a gross
of the
a significant
fluid at the venous
end of the capillary
be carried
off by the lymphatics.
This
in marked
hemoconcentration
hemoconcentration.
Obviously,
cells,
to cause
than
found
pressure
normal
resorption
of tissue
and all tissue
fluid must
in white
sufficient
of hemoconcentration
to understand.
been adequately
explored.
Our results
confirm
the
increase
in which
occur.
degree
in excess
concluded
that
was impossible
should
of only
body
by Castle8’
that
the spleen
the
the
REFERENCES
1
FAHRAEUS,
R. : The
suspension
stability
stability
of the
2 -:
The
suspension
-
: The
erythrocytes
3
4 BERGENHEM,
B.
,
AND
Berurchsichtingung
5 GXNSSLEN,
M. : Uber
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In-
From www.bloodjournal.org by guest on February 11, 2015. For personal use only.
1949 4: 1033-1038
THE EFFECT OF STASIS OF BLOOD IN VARICOSE VEINS ON
ERYTHROCYTE FRAGILITY, WITH ACCOMPANYING STUDIES COMPARING
RED CELLS AND OTHER BLOOD ELEMENTS WITH CUBITAL VEIN BLOOD
STACY R. METTIER, JOHN C. WEAVER and ALICE F. MCBRIDE
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