From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
Shortened
Platelet
By Elke
Various
defects
being
in platelet
associated
multiple
patients
and
1 5 healthy
survival
using
in vitro
averaged
controls
serum
platelet
factor
indices
T
of
1 07
to cause
overt
platelet
counts
pathological
range;
is
patients
patients
logical
impaired
although
bleeding.’
in
in the
l0/L
in
frequently
case
13%
and
platelet
observed
material,2
of
in
delayed
clot
malities
in platelet
retraction,3
and
fibnin
polymerization.”8
have
also
certain
studies,
the degree
of functional
lated with the amount
of panaprotein”#{176}
present.
Shortened
platelet
half-life
has
Abnor-
been
observed.
impairment
or of total
been
reported
patients,
attempted
increased
amounts
of circulating
reversible
parameter.
reports
platelet
aggre-
gates
in multiple
myeboma’3
determined
by the aggregation
index according
to Wu and Hoak.’4
Both main pathways
of
platelet
elimination
were tested:
we calculated
the spleenliver
hal
index
as indicator
system
tens
(RES),
of platelet
globulin,
a
ofdegradation
and
we
quantified
activation)
proposed
the
plasma
indicator
of
Included
Patients.
multiple
From
myeloma
the
AND
investigation
male,
15
Department
of
female)
Medicine
Supported
Ludwig
Submitted
Address
University
J 986
(e)
in the
one
cell
patients
showed
25
within
the
in part
Boltzmann
April
reprint
by
A ustrian
Institutefor
10. 1985;
requests
accepted
had
or steroid
paname-
intravascular
L II,
30 patients
15 healthy
University
with
controls
of
Vienna.
Research
Grant
Gerontology,
P4999
8. 1986.
13. A-1090
II. Dept
Vienna,
and
been
IgG,
with
five
at
and
standing.
with
time
In case
nor
two
light
chains.
nine
in whom
multiple
of treatment,
at
with
paraprotein
of diagnosis,
I 1 patients
administered
marrow
Twenty-
and
of
lambda
the
multiple
bone
IgA,
62.0
following
lesions.
distribution
and
patients
compounds
of
three
(2)
bone
all
and
Diagnosis
seven
patients
from
group
out of the
osteolytic
light-chain
been
obtained
patient
M-component,
(3)
kappa
of long
had
be able
involved.
least
cytostatic
four
controls
had taken
for at least one week.
weeks
before
aspirin,
indo-
anticoagulant.
Platelet-rich
plasma
was
for ten
minutes
supernatant
at
1 50 g for five
500 g for an additional
ten
minutes
tion
of the
fraction
suspended
in
supernatant
I mL
autologous
of
Tyrode
was
short
half-life
exposure
of
2.83
days
as compared
platelets
into
the
platelet
6.2,’
Labeling
reduced
pellet
Austria),
of
platelet
the
rinsed
the
performed
a
because
burden
labeled
which
while
was
Seibersdorf,
at 37 #{176}C
After
and
were
pH
at
pellet,
was selected
‘1Cr.19 The
for five minutes
platelet
buffer,
its
centnifuga-
Centnifugation
the
saved.
that
and
with
washed
minutes.
(SGAE,
isotope
by sedimentation
at 22 #{176}C
and
yielded
plasma
with 100 zCi
Uindiumoxine
gamma
radiation-emitting
obtained
radiation
suspension
inverted
with
of its
test
warm
resuspended
in autologous
plasma
cubital
Radioactivity
recovered
patient’s
vein.
tube
buffer,
and
in
whole blood one hour after reinjection
was 72% ± 6% and served as
the 100% reference
point. At least six additional
samples of whole
blood
were
collected
in EDTA-containing
test
tubes
(Greinen,
FRG)
at
precisely
recorded
intervals
after
injection
of
labeled platelets.
The intervals approximated
as closely as possible 3,
6, 9 or I 2, 24, 30 on 36, 48, 54 or 60, 72 or 84, and 96 on I 20 hours.
All samples were simultaneously
evaluated
for residual radioactivity
in a gamma
counter
(LKB Wallace,
Helsinki).
The resulting
data
were tested
for linearity,
and the optimal
regression
estimates,
derived
from
(Institute
a multiple-hit
gamma
of least squares,
of
Medical
function
model,
were
fitted
by
using SAS#{176}
on an IBM 43 41 computer
Computer
Science,
University
of
Vienna).
Only in cases of short platelet
half-life
was a nonlinear
functiondue to the fraction of residual free radioactivity
in the blood-noted
Vienna.
to Dr H. Ludwig.
of Vienna.
Garnisongasse
by Grune
& Stratton,
Inc.
No.
of two
of the disease,
of the erythnocyte
N#{252}rtingen,
were
year
marrow
Methods.
To evaluate
platelet
half-life,
the method of Hawker
et aP’ was used: 16 mL of blood were collected
without stasis; 4 mL
of 0. 1 5 mol/L
acid citrate
dextros&’
were added
simultaneously
as
neinjected
platelet
subjects.
ten
and neither
or related
the labeled
other
with
drugs
(among
and
April
first
control
with
included
bone
should
was
in the
presence
The
cases
Examinations
of the
studies
consent
years
>15%,
myeloma.
plate-
Inc.
or urinary
presented
light-chain
far
activation
develops
processes
62.6
on the
infiltration
thoroughly
of fl-thrombo-
based
( I ) serum
plasma
capacity
Informed
was
platelet
in shortened
Further
& Stratton.
age
paraprotein
initial-so
thrombocytopenia
pathophysiologic
female).
of
to
correla-
and
an
manifests
overt
age-matched
was
findings:
finally
exhausted.
six
half-life
process
that
comparable
statistical
suggest
compensatory
Median
the method
0006-4971/86/6802--0034$03.OO/O
514
male,
incubated
Austria.
the
(nine
was
METHODS
in this
(15
the
No
platelet
that
becomes
was
15,6
MATERIALS
when
finally
were
group.
findings
It seems
in the reticuloendothelevels
between
consumption
was
of
however,
control
Our
let half-life.
testing,
methacin,
correprotein5
in certain
we determined
to evaluate
this
to confirm
or to refute
previous
and
myeloma
In
pathological
conditions,
including
neoplastic
growth
of solid
tumors,
as well
as in hematological
malignancies.”2
Because
our review
of the literature
indicated
that platelet
half-life
had
so far
not been
investigated
in multiple
myeloma
We also
found
myeloma
of platelets3’5;
reduced
platelet
bleeding
time”4;
impaired
on
metabolism9
healthy
unexplained-intravascular
years
diagnosed
(n = 100): this ratio nose to 40% in terminal-stage
(n = 50). Apart
from quantitative
deviations,
pathofindings
of platelet
function
have also been reported:
adhesiveness”35;
and adenosine
diphosphateor
collagen-induced
aggregation
factor
3 release3’6;
prolonged
was
Sinzinger
indices.
of the
subjects.
enough
we found
newly
Helmuth
to elucidate
the
0 1986
by Grune
counts
severe
and
spleen-liver
only
patients,
aggregation
it is seldom
In our own
below
half-life
In myeloma
and
Myeloma
concentrations.
of the
B2. fl-thromboglobulin.
Scheithauer,
tion
with
half-life
in Multiple
those
platelet
platelet
elevated;
myeboma,
as
myeloma
kinetics
platelet
hours.
HROMBOCYTOPENIA
multiple
reported
30
platelets
significantly
the
Werner
investigated
in vivo
while
thromboxane
within
In
shortened
4 were
were
been
the
hours.
averaged
levels
have
we
measuring
73
Ludwig,
of autologous
Significantly
patients
Heinz
myeloma.
controls.
labeling
and
radioisotope.
healthy
function
with
‘11indium-oxine
Fritz,
Half-life
of Medicine.
Austria.
at the
tail
statistically
ring
well
of the
curve.
significant
below
In these
change
the
instances,
in the
half-time
slope
the
first
appearance
function-always
mark-was
defined
of a
occur-
as
the
cutoff
point.
Blood,
Vol
68,
No 2 (August),
1 986:
pp 514-520
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
PLATELET
HALF-LIFE
The
spleen-liver
reinjection
MULTIPLE
index
was
of labeled
tigraphy
in
interest,
view.
registered
obtained
515
determined
I 8 to
platelets,
anteropostenion
counts
MYELOMA
autologous
the counts
actual
IN
using
After
in the splenic
over
the
liven
the
method
globulin
described.’4
of
area
divided
to yield
and
available
platelet
Plasma
factor
were
difference
was detected.
scm-
regression
analysis,
operations
necessary
at
carried
by the
using
ulation,
technique.2’
and
I mg/mL
Two
percent
EDTA
acid
Center,
these
from
seven
ensured
anticoag-
as a blocker
of
cyclo-oxygenase.
Clinical
serum
protein
component,
the
count.
disease,
as well
calcium
Additional
and
data
of platelet
extent
evaluation
of
and
were
sex,
lesions
formula
aspirations
duration
of the
by
estimated
by Dune
and
at the
In
time
of
testing.
Statistical
or
testing
after
plasma
quantitative
frequencies.
linear
logarithmic
(<70
Mean
values
calculated.
multiple
data
contingency
correlations
of renal
all patients
for skewed
t
as
test; for
were
interconnelations
of platelet
of data,
B2 were
the
level
of
compared,
using
from
Pearson’s
on relevant
serum
creatinine
a
parameters
was
findings
of 20
the magnitude
of each data item in relation to
population.
Mean
coefficients
of variation
were calculated
for normally
distributed
data,
distributions
results
were
expressed
as percentiles.
within
as
Ratios
Table
1 . Paramete
No
rs of Platelet
significant
Functions
of
types of kinetics
platelet
half-life
obtained
example
with
a
fested
variances
and
standard
Platelet
half-life
Platelet
count
However,
in the steeper
evident
in Patients
72.96
only
certain
function.
that
the
103,O124oL
0.62
1.50
±
Aggregationindex
0.68
± 0.10
/3-Thromboglobulin
factor
Median
and
4
not significant.
Platelet-poor
tPlasma.
for
platelet
count
difference
64.64
±
18.45
26.12
±
8.05
hr
plasma.
B2
80
(<70-
156)
the
mean
platelet
and
group,
and
and
and
the
half-life
in the
amounts
that
to only
no significant
control
group
spleen-liver
indices.
were
The
aggregation
index in the control
population
approaches
the
expected
normal
index of I , while its significant
reduction
in
the patient
group
indicates
the presence
of reversible
circubating
platelet
microaggregates.
99 g/L,
With
respectively.
Multiple
Myeloma
107.33
224,600
ng/mL’
ng/mL
pg/mLt
by
is mani-
Values
Mean
for
higher
activa-
in
patient
the
was elevated
coefficients
and Healthy
platelet
to 22, 24,
ofvariation
Controls
SignifIcance
±
9.26
±
104,0844oL
hr
P<
iO
NS
1.47
± 0.26
0.95
±
0.04
24.53
±
5.94
ng/mL
10.47
±
2.98
ng/mL
P<
P<
P<
pg/mL
P <
NS
i0
108
range
Thromboxane
NS.
24.72
±
of
with
(r2 median,
.937;
at 50% of residual
each of the two
reduced
patient
Controls
(N - 15)
±
Spleen-liverindex
Platelet
evaluation
functions
accounted
of the
in the control
between
in
to
and it may well be taken
as an
Kinetics
in the other
patient
only
32 hours
are obviously
is significantly
of the mean
observed
the
slope
I makes
group
68%
In the
deviation
253,650
in
observed
in the patient
group.
In one patient,
was 103 hours;
the plot corresponds
to those
in the control
group,
of normal
findings.
platelet
half-life
of
patient
range.
linear
regression
model
were sufficiently
high
range,
.690 to .992) tojustify
interpolation
radioactivity.
Figure
2 gives one example
Patients
(N - 30)
Mean
l0)
<
to be skewed
serial
yielded
and
I 06 controls.23
normal
in controls,
blood
previous
involving
were
decrease.
Median
platelet
is 75.5 hours, ranging
from
Because the sample of 1 5 test series from our I 5 healthy subjects
was relatively
small, we compared
the data on platelet
half-life
in
these I 5 healthy controls
with age- and sex-matched
values from a
study
(P
appears
pathological
patient
group
well
slopes.
the
tion
parameters
were
significantly
group
than in healthy
controls.
In three patients,
serum
creatinine
comparable
matrix
plot
shorter
distribution
in whole
differences
function
with
the left, indicating
half-life
of the total
Table
The
statistics.
evaluated
and
three-dimensional
significantly
half-life
23 patients,
pathological.
involv-
coefficients.
influence
and determining
total
patient
mean]/SD)
semi-
correlations
Bonferroni
were
of
processed
Student’s
set
to
on thromboxane
while
by selecting
using
a single
according
correlation
Possible
while
within
corrected
test,
therefore
product-moment
from
either
results
B2 included
were
compared,
resulting
comparisons
was
chi-square
g/L
the
([X
were
Only
thromboxane
and
Pearson’s
semiquantitative
tested
of
pg/mL)
For coefficients
significance
distributed
transformation.
concentrations
values
correlations,
ing
All data were normally
evaluation.
inherently
values
varying
cell
Salmon.22
performed
the
two groups.
Platelet
half-life
in the controls
ranged
95 to 122 hours,
with a median
of 106 hours.
In only
of the 30 myeloma
patients
(less than 25%)
were the
radioactivity
x-ray
tumor
was
30 to 110 hours.
In patients
as
with
(determined
were
M-
peripheral
correlations
age,
and
total
urinary
and
for possible
bone
to the
and
levels,
scintigraphy),
marrow
included
as serum
checked
osteolytic
according
bone
methods
hemoglobin
function
whole-body
calculated
I 5 patients,
by routine
concentration
parameters
load
determined
serum
platelet
half-life
remaining
parameters
to generate
multivaniate
analysis,
multiple
myeboma
patients
than in healthy
controls
(Table
I). Figure
1 shows
the distribution
of individual
values
in
commercially
served
stepwise
discniminant
out on the IBM 43 41 computen.#{176}
Platelet
fl-thnombo-
(Radiochemical
of acetylsalicylic
and
RESULTS
Amersham,
UK, and Abbott, North Chicago,
Ill). Plasmatic
thromboxane B2 was measured
in unextracted
plasma samples using the
double-antibody
Computer-assisted
cluster
index.
Hoak, a proposed
was determined
of
evaluated,
systems
after
regions
a dimensionless
concentrations
4 were
radioimmunoassay
hours
insertion
The aggregation
index according
to Wu and
measure
of reversible
circulating
microaggregates,
by
24
computerized
<70
(max:
<70)
.001
and
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
516
FRITZ
130
ane
120
..
110
C.
S
In
‘#{176}
S
60
LU
the
between
50
factor
group.
are
of platelet
count.
control
group,
all available
shown
function
paraprotein
sex,
(all
2. The
intercor-
between
platelet
investigated.
were
associated
were
parameters
and age).
with platelet
AL
however,
in Table
intercorrelations
data
4),
are strongly
could be detected
clinical
parameters
of serum
platelet
tion, platelet
count,
correlated
significantly
=
-
lower
platelet
of the patient
correlations
results
amounts
with
range
but no correlation
and any of the
High
.1.
80
:
significant
related,
half-life
and
the 95%
pathological
90
-
within
All
.#{149}.
.3.
U)
B2, fl-thrombogbobulin,
were
ET
only
calculated
of platelet
func-
Only 3-thromboglobulin
factor
4 (r = .772).
If,
-I
by partial
40
the
Q.
30
correlation,
patient
half-life
are
20
-
10
group
with
and
PATIENTS
Fig 1 .
The median
half-life
of “‘indium
oxine-labeled
control
platelets
(n - 1 5) is 1 06 hours.
while
the median
half-life
of
platelets
from patients
with multiple
myeloma
(n = 30) is significantly shortened
to 75.5 hours (P < i0).
percentiles
for
protein,
bone
load,
serum
lesions,
tions
count,
the
creatinine,
two
creatinine,
protein,
load,
cantly
and bone
higher.
function
the
disease,
hemoglobin,
plasma
half-life,
index,
factor
thromboxane
4 showed
patients
with
In
the
24
serum
calcium,
regression
(spleen-liven
index,
ane
B2 was
sufficient
predicted
with
eliminated
were
fl-thrombogbobulin,
cell infiltration
platelet
half-life
both
22
g/L
of
total
tumor
were signifiand platelet
index,
thrombox-
and
comparing
cant
differences
according
the
in
70
half-life
heavy-chain
fell
7%
(two
below
these interesting
with cutpoints
for platelet
count.
(A)
but
compensated
platelet
HOURS
AFTER
Fig 2.
Kinetics
of radioactivity
patients:
Open circles
represent
cases with normal
platelet
half-life.
the linear function
is well fitted
The closed
circles
are derived
half-life
is severely
shortened
to
linear
(r2 = .824) with the possible
70
80
90
100
110
12C
REINJECTION
in whole
blood
from
two
a typical
clearance
function
in
Platelet
half-life
is 1 03 hours,
to the observations
(r2 = .953).
from
a patient
whose
platelet
32 hours. Again. the function
is
exception
of the lowest 25%.
classes
or
in
perfectly
to the
actual
those
diag-
count
Being
the
range
Patients
platelet
normal.
too small,
interesting
mation
comparison
in
were
no signifi-
did
stratification
types
variables
count
in
of
observed
of
(C),
peripheral
increased
ie,
of <lO”/L)
77%
healthy
then
(23
was
patients),
controls.
patients
platelet
(C)
To
trace
(A)
between
platelets.
platelet
count
abnormally
(premature
loss
of
half-life
as well
as
half-
not observed
are shown
in Table
did
not allow
overt
and
platelet
activation
normal
platelet
possibility-normal
However,
reduced
to one of three
as
half-life
platelet
fourth
subgroup
with
well
normal
or
The
assigned
as
count
for);
(B)-compensated
significantly
with
treatment,
bight-chain
while
life concurrent
with thrombocytopenia-was
our patient
sample.
The main results
group
(1)
under
the
(platelet
cases),
(B)
platelets
60
almost
model
of all variables,
between
decreased;
shortened
50
are
Neither
half-life
10
40
plane
platelet
20
30
B2,
findings,
we dichotomized
the two variables
at 90 hours of platelet
half-life
and at l0”/L
groupings:
pathologically
20
two
of measurement,
depicted
values
thrombocytopenia
observed
10
those
not shown).
80
30
not
is demonstrated
errors
observed.
discriminate
Overt
40
mean
were
to
(data
50
to
do
from
is satisfactory
(r2 = .866).
Dividing
the patients
into two subgroups,
nosed and not yet treated
and (2) patients
90
0
paramethat-as
thromboxane
half-life
fit of the
other
derived
platelet
formula,
could be
data
paraprotein
60
All
between
of random
The
variance.
half-life-they
information
of the regression
functions.
total
indicating
variable
smoothing
dimensions
linear
the
func-
of thrombox-
100).
<
=
the suspected
of platelet
of the
procedure,
interrelationship
and
3. After
(P
4
r
and
shown).
analysis,
72.6%
independent
index,
Fig
accuracy
to
factor
.05
<
in the regression
and platelet
survival
by the
of the
platelet
concentration
to explain
high
spleen-liver
with
plasma
in
of platelet
P
parameters
By including
fl-thrombogbobulin
the results
could be improved
tens
not
various
confirmed:
add
100
;
be
This
patient,
aggregation
could
parameters.
values
for the duration
of the disease,
serum
M-component,
serum
calcium,
marrow
plasma
His values
for
tion
of the
with
.424,
-
=
(data
multivaniate
significantly
of serum
and
r
is eliminated
correlations
By stepwise
tumor
g/L
specific
/3-thrombogbobubin
infiltration,
99
the
proportion
are
prediction
B2, f3-thrombono significant
devia-
and
third
total
serum
cell
platelet
respectively.
serum
serum
of
marrow
aggregation
and platelet
in
duration
M-component,
bone
platelet
platelet
globulin,
age,
shared
calculated,
the results
.463, P < .02, respectively
interdependence
CONTROLS
this
platelet
for the
compensated
not
only
in
3.
most
deci-
did
sub-
half-life-present
when
half-life
compared
values,
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
PLA’LET
HALFLIFE
IN
MULTIPLE
MYELOMA
517
Serum
Platelet
P’z:,001
count
Spleen.I,ver
82 life;
the
Significantly
gIobl
and
shorter
than
Was
in
factor
(13) and
Multiple
cation
platelet
normal
of conditions
because
values
favorable
outcome
the
sub-
trivial.
cell
infiltration
platelet
was
compensa
(data
determined
were
within
Percentages
r
by
.646
eral
platelet
(r
702)
and
cells
normal
included
in
infiltration
correlated
M-compo
tumor
index,
and duration
.784).
counts
Theoretically,
life may b traced
found
Fig
3.
Interrelations
between
Platelet
haIfIjfe.
.02
also
The
inverse
exceeded
the
thromboxane
B2.
and
fl-thrombogo1.
normal
Platelet
halflife
B2 and fl-thromboglobl.
sample
Bone
limit
with
peniph
of significa
DISCUSSION
a Pathologic
shortening
of platelet
halfto one of two basic causes:
to an intrinsic
Front:
Low
plasma
concentrations
Rear: Ihe lowest
platelet
hafflives
The plane has been derived
from
3%
in the only
significant’y
with
mass
per m2 body
of the disease
(r
correlation
the
second
from
IN
thromboxane
B2 and fl-thrombogo11
are associated
with
concomitantly
with the highe5
plasma levels of thrombozane
after smoothing
of random
errors of measurement.
-
in the bone
the
160.00
BETATHROHBOCLOBU1
=
P-z:
ofplasma
patient
marrow
plasma
cell
serum
calcium,
urine
surface,
spleen_liver
smears
from 1 1 patients
and from
four patients
clearance
.408
were
29,5 for the fIrst and
12,0 for
The values
for all 1 5 patients
ranged
91%, the highest
Percentage
determined
thrombocyopj
identifi
inconclusive
Median
marrow
subgroup
through
between
plasma
-
rP<.02
=
.453
range,
it
highly
in
is logically
impeding
was
the
State
Permitting
loss remained
r
P’(05
<,001
r=
r = .823
.8 1 9
P’z:,001
(A),
half-lives
patterns
39
=
differed
survival
not
to or
platelet
of
r
.666
/.I-thrombo
platelet
platelet
this
(C)
plasma
We did
differential
counts
of bone marrow
platelet
half-life
<90
hours
50%
to
of subgroup
with
whose
r
.05
.823
-
patients
bracket
for POSsible
of accelerated
subgroup
4. Although
two
r
.819
regard
comparing
searches
not shown)
Bone marrow
in
in the
of
(C)
r =
<,001
“normal”
controls
result
groups
tion
apparently
from
P<.001
r = .935
r
.935
p<,00,
r P<.001
=
.852
the shortest
signific
0lsease
P<.001
r=r P<.OO1
-.783
_
722
lateletlf
Thromboxane
Bone
.426
index
PnZ.00l
not
_
=
P<
Plateletfactor4
Thrombogg01,
also
r
index
Aggregaj0
but
p,,001
Urinary
of
are obseed
the actual data
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
FRITZ
518
Tab Ic 3.
Parameters
o f Platelet
Functions
A
Platelet
half-life:
Platelet
Platelethalf-life’
hr
B2t
93
/3-Thromboglobulin
1 .900
(<70-1
247,
16)
>90
68.4-16.0
29.4-7.2
2
an d Platelet
hr
Count
Significance
ioo,ooo
>
NS
P
(<70-156)
24.5-3.9
N
Half-life
C
Controls
104.6-4.2
100-60,800
96
60.5-12.8
Plateletfactor4’
Significance
B C
59.5-16.7
70,500-2
Thromboxane
hr
ioo.ooo
>
70.0-17.1
Platelet count
by Platelet
AL
C
<90
ioo,ooo
<
Grouping
B
<90
count:
A fter
ET
<
309,900-
.01
<70
Controls
NS
139,200
107.3-9.3
NS
224,600-82,200
NS
(<70-80)
<70
(<70)
P<
.001
42.9-9.9
P<
.001
24.5-5.9
P<
.001
19.1-6.0
P<
.001
10.5-3.0
7
21
15
NS, not significant.
‘Mean
SD.
-
tMedian
(range).
defect24
of the
platelet,
the
spleen
or at other
an
extrinsic
defect,
accelerated
operate
uted
to premature
ie,
sites
blood platelets
an abnormally
consumption.’5’25
observed
in our
unequivocally
destruction
of RES
environmental
platelet
loss. Extrinsic
by two fundamentally
either
rendering
tion or effecting
platelet
half-life
leading
prominent
conditions
factors,
different
or to
effecting
in turn, may
mechanisms:
also
by
more vulnerable
to degradahigh rate of intravascular
The significantly
myeloma
patients
to one
in
activity,
or the other
shortened
cannot
of these
intrinsic
impairment
clone
of megakaryocytes,
tively
inferior,
resulting
from
ment
can
due
possible
be assumed
to cause
reduced
Although
half-life
and
the absence
paraprotein
influences
environ-
platelet
survival
multiple
myeboma.
Seeing
the findings
obtained
in the light
of these
hypotheses,
it is challenging
their value in providing
possible
explanations.
of correlation
concentration
to
be
in
support
the assumption
of a fraction
present
among
with
distinctly
resulting
of pathological
normal
specimen.
different
slopes
hyperbolic
function
would
not permit
fit of a linear model to the observed
data points.
of the clearance
function
suggests
a uniform
platelets
with fairly constant
survival
times.
When
considering
external
factors
that
adverse
influences
on platelet
chemotherapy
constitutes
platelet
half-life
in patients
from
that
in patients
correlation
platelet
ment
survival
not yet
between
duration
clearance
cytostatic
drugs
appear
survival
an
also
nor
could
possible
to be responsible
myeloma.
platelets
If two survival
were
combined,
that
The
of the
not
be
lets,”35’7”#{176}which
may
negative
of
Neither
treat-
in this
regard.
it is the
as
In this
quality
determines
The spleen-liver
those
rather
the effect
indices
of platelet
amount
of paraprotein
such,
observed
in
than
Unexpected
the
from
or free light
of the previous
chains
stud-
macrogbobuwith
light-chain
specific
conclu-
the
paraprotein,
frequent.2’26
quantity
and
Possi-
of paraprotein
controls;
population.
did not differ
there
or
observation
to note
cell infiltrationwith the duration
the tumor
cells, to
it has on the platelet
in our patient
group
healthy
to
effects
it is interesting
sequestration
was
seems
detrimental
connection
of extraordinary
the other
hand,
found
concurrently
platelet
to
were
no
degradation
that
the
of
parame-
were significantly
increased,
even
still showed
normal
life spans.
On
in no patient
was reduced
platelet
half-life
with normal
values
in all parameters
of
activation.
elevated
serum
levels
ished renal clearance
We
ruled
of platelet
in patients
out
the
possibility
factors
were
with impaired
that
the
due to diminkidney
func-
tion.
on abnormal
cell dyscrasias,
to paraprotein
enhance
total
tens of platelet
activation
in patients
whose platelets
half-life
according
necessarily
rule out all
on the platelet
popula-
we excluded
cases of WaldenstrOm’s
and the number
of our patients
was too small
to permit
drawing
indications
in multiple
In previous
reports
patients
with plasma
were mostly
attributed
the
relevance
However,
not differ
of steroid
shortening
though
platelets.
confirmed.
consequences
for the
and
amounts
unable
to
the amount
of
of platelet
func-
subgroups
light chain8 could be detected.
findings,
however,
do not
of the plasma
M-component
myeboma,
expected
disease
between
parameters
into
significant
increased
we were
class
on bight-chain
type
of the paraprotein
yield any significant
results.
No association
of any
feature
of platelet
pathology
with IgG,’#{176}IgA,’
or
little
from
obvious
possibility.
under
treatment
did
stratification
(ie,
some extent,
lose their capacity
to secrete
deviant
antibody
molecules
become
more
bly
exert
to destruction.
highly
that-in
contrast
to bone marrow
plasma
panaprotein
concentration
did not correlate
of the disease.
As myeloma
progresses,
The linearity
population
of
might
susceptible
exhibited
immunogbobulin
aggregates,
polymers,
have to be considered.
Unlike
most
a satisfactory
in multiple
treated.
functhe
did
Even
of
sions
environmental
factors,
the data
collected
on serial
of radioactivity
in the patients’
blood
fail to
more
collective
in the aggregation
indices
circulating
microaggregates),
Non
linemia,
myeboma
platelet
argue
them
patient
the proposed
correlation
or urine paraprotein
and
j5,46I3
against
evaluation
being
tions
confirm
serum
tion.
in our study
to weigh
between
appears
reductions
of reversible
lambda
These
influence
to a disease-associated
which
produces
qualita-
or even defective,
platelets,
and
the distinctly
abnormal
intravascular
our
heavy-chain
molecule
observed
causes.
Both
deviant
or render
Although
tion.
platelet
be attrib-
three
aggregates
their
platelet
function
in
the observed
defects
coating
of the platetendency
to form
micro-
plc
Our findings
myeboma,
mere coating
not activated
do not support
the assumption
that
premature
elimination
of platelets
in multiis due to
or cross-linking
of inert platelets,
ie, of platelets
and not exhibiting
release
reaction.
It rather
From www.bloodjournal.org by guest on June 18, 2017. For personal use only.
PLATELET
HALF-LIFE
IN
MULTIPLE
appears
that initially
ing the platelets
takes
some intravascular
place. Our data
of such
a proposed
platelet
threshold
platelet
before
half-life.
it manifests
A
second
compensate
indicated
MYELOMA
process’5”6
activatsuggest
that the extent
activation
threshold,
519
has
to exceed
as a measurable
in the
bone
platelet
half-life
fell below
the
a certain
of
capacity
to
appears
to be
of our patients,
only
less
than
10% showed
overt
thrombocytopenia.
Unfortunately,
we had
not included
bone
marrow
examinations
in
our
them one of the two patients
with thromboprocedure
was performed
concurrently
with
merit
of platelet
does
not
function.
allow
consideration
necessity
tein
that
cells
plasma
alone
permit
not
grounds:
half-life
secrete
does
the
in general,
larger
with larger
but there is no
Our
findings
is not correlated
with
parapro-
following
amounts
conclusion:
of panaprotein,
a greater
hazard
population.
However,
the significant
high percentage
of bone marrow
tumor
this
to the
fact
correlation
between
cell infiltration
and
adequate
amounts
their premature
Even though
of platelets
in compensation
peripheral
elimination.
the magnitude
of platelet
activation
on the test
between
being
used, our interpretations
patients
and controls
observed
identical
conditions.
The
gates,
as proposed
artifacts
due
fixed
platelets
by
Wu
ofdetermining
and
Hoak,
rely on
under
microaggre-
is prone
to the passive
participation
in aggregation27
so that
to produce
of
independent
the
platelet
processes
leading
from
capacity
overt
a slight
There
extent
platelet
take
Future
investigations
are
of intravascular
and for relatively
boss to become
differential
counts
of a primarily
affected
by
labeling
experiments
observed
plasma
globulin
interrelationship
concentrations
be confirmed,
clinical
routine
the
risk
of
of the
they
marrow
platelet
should
smears.
The
population
could
allogeneic
possible
and
influences
using
marrow
infiltration
to determine
bone
normal
environmental
bone
activation,
of
a second
severe
needed
platelet
to
diminu-
apparently
place:
to a
seems
for this
thrombocytopenia,
of
in
or moderate
to compensate
must
the
possibly
also
be reflected
half-life.
pool to a large
the continuous
process
population;
and
may
depression
as a consequence
of massive
bone marrow
by myeboma
cells.
be
platelets.
being
tested
by
Should
the
between
platelet
half-life
and
of thromboxane
B2 and fl-thrombosimple
screening
assays
included
in
examinations
may
thrombocytopenia.
It
be sufficient
would
to monitor
be
of
particular
to include
in future
studies
all thrombocytopenic
without
overt
bleeding
complications,
in order
determine
the
conditions
necessary
platelet
loss. If the processes
physiology
associated
with
fully
of formaldehydethe indications
the
as
or
the
of platelet
of the platelet
periods.
For
interest
patients
findings
depends
differences
method
for
by
explaining
consumption
destruction
time,
however,
hypothesis
platelet
activate
shortening
include
low platelet
count suggests
that the progression
of the disease
may play a key role in the capacity
of the bone marrow
to
provide
exist,
agents
if more
to
survival
event
short-
confirmed
a model
the ensuing
extravascular
manifest
results
to be
propose
appears
extent
of
increased
tion
long
number
the
stimulus
pronounced
15
correlation.
the
constitute
in
small
conclusions,
a linear
platelet
concentration
but
appears
to be associated
cells in the bone marrow,
to presuppose
showing
Although
for definitive
on theoretical
ened platelet
half-life
numbers
of myeboma
feature,
need
involved
in the reduction
of platelet
half-life
and the eventual
manifestation
of thrombocytopenia
in myeloma
patients:
very early
in the course
of the disease,
some intravascular
platelet
patients-among
cytopenia-this
testing
general
while
plan
the
a
range,
investigational
of cases
as
normal
aggregation
investigators.
We tentatively
shortening
marrow’s
for increased
platelet
consumption,
by the fact that in more than 75%
platelet
elucidated,
more
lion-of
overt
become
possible.
to compensate
involved
multiple
efficient
in the
myeloma
platelet
can
treatment-on
thrombocytopenia
in
the
pathobe more
even
multiple
to
for
preven-
myeboma
may
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1986 68: 514-520
Shortened platelet half-life in multiple myeloma
E Fritz, H Ludwig, W Scheithauer and H Sinzinger
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