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Development
of Factor
Alan
By
Classic
hemophilia
nosed
A
cryoprecipitate.
rhagic
events.
canine
factor
carriers.
bred
VIII:C.
miniature
Schnauzer
The
exposure
mean
at the
286.3
U.
mals
have
mean
factor
animals
at
of inhibitor
developed
VIII
derived
female
treatment
and
a mating
to
obligate
Brittany
factor
despite
bodies
recognize
VIII:C.
They
inhibitor
precipitate
was
hemostatic
animals
wk
oped
ani-
receiving
a
antibodies
philia
complicated
purebred
factor
VIII:C.
included
hemophilic
Omaha,
NE.
a purebred
spaniel
a single
purebred
mechanisms
development
(11.4).
native
VIII
modes
of
replacement
tion. The
in their
and
alter-
management
to conventional
have
received
considerable
incidence
of inhibitors
is highest
factor
atten-
inherited
a suggested
compatibility
more intensive
propensity
association
loci was
study.56
In recent
years,
program
of hemophilic
not
we
development
of
this article,
development
we present
ofantibodies
factor
subsequently
bleeding
cuticle
VIII
factor
VII
with
Whereas
the
have
developed
a breeding
dogs in order
to facilitate
the
deficiencies.78
VIII:C
has
bypassing
information
to factor
therapy.
hemostasis,
In
relating
to the
VIII:C
in a defined
arm of our breeding
program
where
transfusion
exposure of all the animals
concerned
has been confined
to
homologous
proteins.
been
From
the
AND
METHODS
Animals
The
Alpha
shown
in
constructed
kindly
tree
of the
I. The
Fig.
facility
provided
Hematology
Blood,
Fund,
Vol. 63,
breeding
at
by Drs.
Research
animals
currently
program
was
Queen’s
University,
W.
and
Bowie
at the
No. 2 (February),
Mayo
1984:
available
using
D. Fass
Clinic,
pp.
initiated
of the
Rochester,
45 1-456
for
study
is
in a specially
breeding
MN.
Ontario,
of
These
Address
©
was
hemophilic
uncle
and
regular
MO).
as previously
to
with
I 2 mm.
silver
after
cuticle
in
evaluating
time
for
to
the
defects
CBT
should
integrity
not be
practice.
of
primary
coagulation
in primary
was
of the
in clinical
discrete
the
treated
administration
as used
tests
sensitive
still
and
In animals
bleeding
time,
described,7
Cuticles
nitrate,
the
is
of
Queen
June
3N6,
/ 984 by Grune
Pathology.
Medicine.
Kingston
General
from
factor
hemostasis
and
Hospital.
the Medical
Corporation.
Los
Animal
Kingston,
Research
Council
Angeles.
CA.
and
‘s University.
at IXth
International
Stockholm,
6, 1983;
Sweden,
accepted
requests
Richardson
K7L
and
by grants
reprint
Pathology.
stock
Department
with
beagle
Schnauzer
a pretreatment
Therapeutic
in part
Hemostasis,
Submitted
family
a purebred
miniature
(see below),
The
Departments
Presented
and
by
mated
purebred
30 mm
bleeding
‘s University
Ontario,
Canada.
Supported
in part
c
with
of collodion.
specifically
CBT
of
obtained
were
Louis,
the
assessed.
Queen
the Dean
used.
latter
Davis
ad libitum
reduced
application
skin
from
Richard
1
The
Schnauzers
to her
St.
cauterized
repeated
Its role
of (anada.
MATERIALS
the
the
not
Care,
then
back
performed
was
were
I preparation
confused
was
replacement
and
(111.8).
(CBT)
time
by the
same
on water
Purina,
of observation
time
to
Dr.
bitches
female
mated
(Ralston
bleeding
factor
performed
also
of
directed
of hemo-
antibodies
Schnauzer
carrier
maintained
All
occurrence
crossbreds
(111.1 ). The
Time
protected
with
by
chow
by
were
hemophilic
was
the
devel-
female
Clinic
miniature
sire
were
at that
of
recovery.
of
miniature
The obligate
purebred
animal
period
VIlI:C
(111.2, 111.3, 111.4, 111.5),
carriers
hemophilic
animals
cuticle
the
cryo-
factor
chance
hemophilic
Mayo
obligate
Bleeding
The
but
I
purebred
beagle
puppy/dog
canine
subsequently
The
bitches
to the
(11.1).
the
This
All
Cuticle
in hemophil-
for inhibitor
developwith
major
histo-
confirmed
with
(111.8).
dry
iacs with severe
disease,3
but this may relate
only to
reduced
exposure
to factor
VIII
therapy
in patients
with mild disease.4
Familial
studies
have demonstrated
an apparent
ment,
but
mated
of
correction
development
and
were
The
Brittany
it represents
one of the
current
management
of
both
the
pathogenetic
the
carrier
donated
mating
tis B, by multiple
transfusion,
most serious
problems
in the
hemophilia.2
Consequently,
protein.
porcine
and
VIII:C
VlII:C
anti-
of a concentrate
a
factor
factor
(11.4),
animals
stock
optimal
by
male
original
Infusion
in
not
should
facilitate
further
studies
pathogenesis
and management
4 obligate
hemophilic
infusion
resulted
to this
but
mm-
the
immunoglobulins.
ineffective
porcine
this complication
at elucidating
the
same
NTI BOD I ES TO FACTOR
V I I I :C develop
in
approximately
I 0% of all patients
with classical
hemophilia
A (factor
VIII:C
deficiency)
who receive
factor
VIII replacement
therapy.’
Together
with the
risk of transmission
of infective
agents,
such as hepati-
involved
receiving
case.
IgG
negligible.
and
the
A
was
a purebred
human
development.
defect
includes
each
and
hemostatically
VIII
group
between
canine
factor
U. This
and
In
nonprecipitating
at 30 mm
porcine
male
female.
both
are
A
Greenwood
hemophilic
carrier
Following
VIII
10.3
hemophilic
Schnauzer
Hemophilia
and Ronald
Schnauzer
iature
of
With
Greenwood,
recovery
pure-
was
remaining
of 1 .5 x i0
from
of
to a normal
antibodies.
dosage
hemor-
a hemophilic
development
The
with
antibodies
Penny
miniature
pro-
sporadic
offspring
of
diag-
produced
potent
the
first
was
treated
for
mating
respectively.
not
initially
male
age
time
crossbreeding
were
the
Hoogendoorn,
a breeding
were
developed
All
from
and
required.
animals
resulting
spaniel.
and
as
Five
Hugh
and
All
Antibodies
in Dogs
VIII:C
Deficiency)
deficiency)
dog
Inbreeding
animals.
Tinlin,
VIII:C
Schnauzer
established.
hemophilic
canine
Shawn
(factor
in a miniature
gram
16
R. Giles,
VIII:C
(Factor
to
Dr.
Laboratory,
Congress
of Thrombosis
I 983.
September
A.
R.
Queen
2. 1983.
Giles.
Department
‘s University,
of
Kingston.
Canada.
& Stratton.
Inc.
0006-4971/84/6302-003l$Ol.00/0
451
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
GILES
452
ET
AL.
1.
Inhibitor
Ft Treated
t
I.i
12
to Canine
Vlll:c
with Canine Cryoppt
Death
VIII.’C
All
Replacement
hemophilic
animals
hemorrhagic
part
of an experimental
treated
with
Labs.,
protocol
porcine
Nottingham,
powder,
which
was
ately
prior
blood
as previously
the
canine
content
against
of Hyate
This
Blood
provided
formula.7
canine
(see
control
specification)
was
studies
factor
for
w/v),
taken
assays
was
anticoagulated
9 vol of blood to
by a two-syringe
with
I vol anticoagulant.
technique.
The
pool plasma
reference
(collected
standard
factor
Vlll:C
canine
factor
VlIl:C
was
pooled
canine
plasma
with
activity/mI
hr at 37#{176}C.
When
units
(BU)
the
incubation
and
ofthe
antibodies
and
human,
were
same
were
by the
and
used
residual
When
In each
Vlll:C
species
They
was
porcine
in each
factor
case.
the
standard
derived
according
were
of the
factor
was
asthat
gel diffusion
of
defined
technique
VllI:C.
used
test
curve
to criteria
used
to
in assaying
of factor
incubation.
established
as precipitating
plasma
found
were repeated,
plasma
in the
The
by Biggs
or nonprecipi-
of Ouchterlony,’2
Both
of
for 2
following
was
a source
initial
to
in Bethesda
level
the assays
for canine
using
as a
I U of
plasma
animal
in the
used
volumes
expressed
VlIl:C
using
and
antisera
as previously
prepared
VIII:C
serum
chromatography.’
immunoglobulin
homogeneity
anti-canine
Ltd.,
inhibitory
activity
sulfate
Individual
class
rabbit
collected
by ammonium
(Miles-Yeda
Vlll:C
from
inhibitors
against
for factor
by
class-specific
Israel).
was then
Each
in the Bethesda
assay,
described.
canine,
concentrates
RESULTS
All
the
animals,
to treat
factor
Normal
inhibitors
equal
a particular
case,
activity
classified
coworkers.’#{176}”
tating
dilutions
an inhibitor
the
was
presence
to canine
factor
Vlll:C,
human
or porcine
plasma
incubation.
VlIl:C
The
for
hemophilic
canine
animals,
affected.
hemorrhagic
in human
hemophilia
throsis
in the hind
animals
have
had
below).
The factor
sodium
to contain
by incubating
varying
identified,
animals)
considered
plasma.
described.9
factor
25 normal
and
identified
by determining
have an inhibitor
substituting
both
residual
from
throughout
checked
are severely
spontaneous
All blood
prothrombin
partial
thromboplastin
time, thrombin
clotting
time,
Vlll:C
assays
were
performed
as previously
described.7
initial
U
of porcine
accordingly.
coagulation
reassayed
ofFactor
exchange
I U
to 0.125
dose
time,
canine
of
Assays
(3.8%
were
were
anionic
immunoglobulin
was
that
equivalent
the
and
were
Vlll:C
factor
material
suggested
described,
fractions
with
dog colony.
VlIl:C
porcine
below)
fractions
of hemophilic
Characterization
Immunoglobulin
animals
Pedigree
immunoelectrophoresis
whole
quality
a
Fig. 1 .
precipitation
immedi-
canine
Male
from
lyophilized
dose
reconstituted
plasma
In the
from
Random
as
were
prescribed
suggested
of the
a
injection
prepared
the
given
Speywood
as
for
case,
produced
was adjusted
Hemophilic
Immunoglobulin
Inhibitor
animals
(Hyate.
water
was
Assay
VIll:C.
Coagulation
was
was
Some
Male
Normal
cryoprecipitate
this
concentrate
with
a standard
canine
Results).
In each
(manufacturer’s
VIII
citrate
samples
U.K.).
normal
factor
factor
VIII
described.7
5 U/mI.
pooled
canine
factor
cryoprecipitate
of
(see
Cryoprecipitate
using
with
In addition,
reconstituted
to use.
determined
treated
as necessary.
Female
Hemophilic
D
U
Therapy
were
events
Carrier
.
J11.i Beagle
Factor
for
Mm. Schnauzer
Mm. Schnauzer
Brittany
Spaniel
who
all
have levels
hemorrhagic
according
the general
male
and
they
similar
female,
suffer
to those
from
seen
A. Scalp
hematomas
and hemarlegs are the most frequent,
but two
major
intnaabdominal
bleeds
(see
VIII:C
levels are <1% in all but two
cryoprecipitate.
adjusted
following
both
Clinically,
events
of <4%.
events
The
dose
Initially,
we elected
aggressively
with
administered
was
to the assessment
of clinical
risk
principles
established
in clinical
practice.’4
The therapeutic
protocol
used included
the
collection
of postinfusion
plasma
specimens
for factor
VIII assays.
Although
not always
processed
immediately,
they were
for retrospective
Development
stoned
at
evaluation.
oflnhibitor
-70#{176}C and
to Canine
were
Factor
available
VI1I.C
As can be seen from Fig. I , 5 of I 5 available
affected
animals
have
developed
inhibitors
to canine
factor
VIII:C.
This was first recognized
in one animal
who
failed
canine
to show
an
cryoprecipitate
adequate
given
therapeutic
for
response
a hemanthrosis
to
in a
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FACTOR
hind
Vlll:C
leg.
ANTIBODIES
453
Subsequent
revealed
specimens
VIII:C
recovery
and
inhibitor
assays
demonstrated
of a potent
Subsequently,
body.
of postinfusion
factor
postinfusion,
presence
assay
negligible
anti-canine
factor
inhibitor
assays
30
the
VIII:C
were
mm
anti-
(9
z
performed
z
routinely
response
on all animals
at 3-mo intervals
or sooner
if
to therapy
appeared
to be inadequate.
The
mean
age
and
factor
VIII
exposure
at the
time
4O
0080
60
w
of first
C.)
demonstration
ofa factor
Vlll:C
inhibitor
was 10.3 ±
5.6 (SD)
wk and 286.3
±
1.56.1
U, respectively.
All
the animals
with inhibitors
are the offspring
derived
from the initial
mating
of the normal
Brittany
spaniel
(11.1)
and
the
hemophilic
purebred
miniature
Schnauzer
(11.2).
In contrast,
none
philic
animals
have
demonstrated
despite
having
received
a mean
dosage
of I .5 x IO U.
Characterization
Each
species
of Factor
inhibitor
specificity
VIII
>
I-
C.)
4
U-
a,
of the other
hemothis
propensity,
total
factor
VIII
IC
for its
Bethesda
potency
assay
and
as
per
activity
by the
unit
against
increased
volume
human
factor
VIII:C
is
level of this clotting
factor
of canine
plasma
in comparison
to
human.
In each case, the antibodies
appear
to be type
II, according
to the Biggs classification,
i.e., residual
levels ofcirculating
factor
VIII:C
(range
I%-4%)
transfusion
of factor
VIII.
A typical
example
of
the inactivation
of the antibody
Preparation
stnated
that
of factor
VIII:C
by varying
is shown
in Fig. 2.
of immunoglobulin
the inhibitory
capacity
Table
1 . Inhibitor
dilutions
fractions
demonresided
in the lgG
Assay
Performed
on Specim
18
INHIBITOR
I
I
24
30
PLASMA(uI)
identification
unavailability
could
not be deterof subclass-specific
anti-canine
antibodies.
The antibodies
developing
after
exposure
to only canine
cyroprecipitate
were nonprecipitating
against
both canine
and human
factor
VIII:C.
Similarly,
the
following
were also
factor
factor
VIII:C
activity
can always
be measured
even
following
incubation
with undiluted
inhibitor
plasma.’#{176}
Similarly,
all animals
developing
inhibitors
had detectable
after
12
Fig. 2.
Dilutions
of the inhibitor
serum
were
made in saline
and incubated
with an equal volume of pooled canine plasma for 2
hr at 37’C. The volume
of inhibitor
plasma
is plotted
against
the
factor
Vlll:C
remaining
after 2 hr. Assayed
as described
under
Materials
and Methods.
fractions.
Subclass
mined
due to the
described
under
Materials
and Methods.
The results
are shown
in Table
I. In each
case,
initially,
the
inhibitor
recognized
both canine
and human
but not
porcine
factor
VIII:C.
The
apparent
paradoxically
higher
explained
6
VOLUME
Inhibitor
was assayed
using
the
20
0
antibodies
recognizing
porcine
factor
nonpnecipitating
Response
First
to Factor
VIII:C
demonstration
of
the hemoglobin
level
In view of the lack
antibody
porcine
Each
of 5 Animals
factor
With
Assay-Bethesda
falling
from
of specificity
VIII:C,
Canine
Chico
(lV.5)
animal
VIlI:C
Pre.
46.4
0
VllI:C
Post.
#{149}
26.0
16.0
27.2
0
19.2
40.0
0
29.0
Spike
(IV.8)
13.6
35.2
0
-
Daryl
(IV.6)
3.6
ND
0
-
Vlll:C
(pre),
all measured
on same
was
Fac tor VIII: C Inhibitors
Drew(IV.7)
Anti-canine/anti-human/anti-porcine
ND,
Human
VllI:C
26.9
the
1 2 to 5
of the
Units
Porcine
Dog
development
suboptimal
response
same
animal
subseintnaabdominal
hem-
ornhage,
with
g/dl
overnight.
for
Infusion
antibody
occurred
following
the apparent
to canine
cryoprecipitate.
The
quently
developed
a catastrophic
Inhibitor
Hercules(IV.11)
VlII:C,
infusion,
species
of
Vlll:C.
In Vivo
ens From
porcine
VIII
concentrate
against
all three
0.8
sample.
not done.
All animals
animals
were
inhibitor
assays
were
tested
subsequently
were
for activity
treated
performed
with
against
canine
porcine
as described
factor
under
human
and porcine
VIII concentrate
Materials
factor
and retested
and Methods.
VIll:C
prior
to treatment
for anti-porcine
factor
with
porcine
Vlll:C
activity
factor
VIII concentrate.
2 wk following
exposure.
Three
The
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
454
GILES
treated
resulted
condition.
with
porcine
in a dramatic
Postinfusion
factor
VIII
concentrate.
improvement
in his
studies
demonstrated
recovery.
He
subsequently
had
factor
VIII
nence
porcine
clinical
2 wk later,
but an identical
protocol,
using
factor
VIII,
resulted
in an initial
suboptimal
response
and insignificant
factor
VIII:C
recovof porcine
factor
response,
although
recovery
at 30 mm
was
of that
25%
expected
time of recurrence,
a low titer antibody
recognizing
porcine
factor
VIll:C
was
now
detectable.
This
became
indetectable
for 2 days following
porcine
facton VIII infusion,
but subsequently
nose to significant
levels. We assume
that the initial
lack of response
was
associated
with the pnesence
of this newly
developed
further
The
and
that
the
subsequent
infusion,
followed
above
experience
response,
following
its saturation.
prompted
us to perform
con-
trolled
studies
using the CBT in order
to obtain
more
definitive
data
as to the in vivo activity
of different
species
of factor
VIIl:C
in the presence
of the antibody
to canine
factor
VIII:C.
The
results
of a typical
experiment
are shown
canine
cnyopnecipitate
uncomplicated
by
in Fig.
into
4. The effects
a hemophilic
inhibitor
( mins)
BLEED
STOPPED
WITH
C
TRANSFUSED
0
CANINE
CRYOPPT.
CANINE
CRYOPPT.
AgNO3
IF
2
FVIll(%)
60
of infusing
animal,
development,
was
com-
pared with an animal
with a demonstrable
inhibitor.
In
each case, an equivalent
dose of factor
VIII:C,
determined
on the basis of body weight,
was given.
Canine
cryoprecipitate
produced
prompt
connection
of the
CBT in the noninhibitor
animal,
whereas
no correc-
I
I I
llIl!l!11II1i111
HYATE
a
postinfu-
Figure
3 shows
these
events
related
to factor
antibody
activity.
It can be seen that,
at the
antibody
Bleed Time
AL.
a recur-
cry at 30 mm. Further
transfusion
VIII
resulted
in a good
clinical
sion.
VllI:C
Cuticle
This
clinical
optimal
ET
*
I I I I I I
I
HEMOPHIUAC
WITH NO DETECTABLE
INHIBITOR
HEMOPHILIAC
WITH
BU.)
INHIBITOR
DOSE CALCULATED
TO GIVE
( 2.2
50%
RISE
IN F.VlII
Fig. 4.
The effect
of treatment
with either
canine
factor Vlll:C on the cuticle
bleeding
time in hemophilic
and without
inhibitors
to canine factor Vlll:C.
or porcine
dogs with
tion
Similar-
occurred
ly, factor
in the animal
VIII:C
recovery
with
the inhibitor.
was
optimal
in the
nonin-
hibitor
animal,
whereas
no factor
VIII:C
was recovened 30 mm postinfusion
in the animal
with an inhibiton. In contrast,
infusion
ofponcine
factor
VIII concentrate into this animal
resulted
in an optimal
response
in
the CBT,
together
with
an equivalent
recovery
of
factor
VIII:C.
Similar
the infusion
of canine
results
were
cryoprecipitate
whose
clinical
course,
concentrate,
is illustrated
ton level
of 27
VIII:C
having
fallen
BU over
recovery
calculated
(> 1 2 mm)
following
in Fig.
porcine
3. Despite
to a low of 1 .75
a period
of 42
was recorded
to give a 50% increase.
was not corrected
at
this observation,
canine
factor
later.
obtained
into
no anamnestic
VlIl:C
antibody
following
the animal
factor
VIII
the inhibi-
BU
from
a high
wk, negligible
30 mm after
factor
a dose
The prolonged
CBT
I S on 30 mm. Despite
response
in the antihas occurred
13 wk
DISCUSSION
30
The development
hemophiliacs
treated
#{176}1
1)
36efl184
w
II
it
a:
t:
.-_.
2O
Anti Canine
Anti
I
EV1II:C Activity
PottineEVUIC
Activity
C
represents
one
hemophiliacs
agement
of the
today.2
I
I
to the
C
potential
for other
this complication.
:
U
I
-Iv
#{163}
May
June
July
counseling
problems
relates
with
of their
affected
Although
to factor
VIII:C
VIII
replacement
in the
not only
with
care
to the
the complication,
relatives
family
members
epidemiologic
of
man-
but
regard
in
also
to the
to acquire
data
sug-
gests a familial
tendency,
we remain
completely
ignorant
as to the
precise
pathogenetic
mechanisms
involved.
Consequently,
the occurrence
of this complication
in an animal
model
of the human
disease
I
April
major
This
of individuals
0
-
I
of antibodies
with
factor
Aug.
Se#{231}f.
Fig. 3.
The antibody
titer in Bethesda
units against
canine
and
porcine
factor
Vlll:C is shown
over time. The vertical
arrows
(1)
indicate
the transfusion
of a porcine
factor
VIII concentrate.
the
numerals
indicate
the total dose infused
(canine
U factor
Vlll:C).
The first and second
infusions
were
associated
with
optimal
clinical
response
and factor
Vlll:C recovery.
The third infusion
was
associated
with a suboptimal
clinical response
and recovery.
promotes
the opportunity
to study
nisms
involved
that
goes beyond
presented.
the possible
mechathe data
currently
Study
of the inheritance
pattern
suggests
that the
propensity
for inhibitor
development
may not be inherited in direct
association
with
the primary
genetic
abnormality,
but
rather
as
a
result
of
its
chance
From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
FACTOR
Vlll:C
association
acquired
ANTIBODIES
with
from an
455
a genetically
unaffected
expressed
function
individual,
in this case,
appears
to promote
or stabilize
the normal
the factor
VIII
complex.’7
Confirmation
function
of
of Gawnyl
the Brittany
spaniel.
We cannot
exclude
that the propensity
is associated
with
Schnauzer
(11.2) and that segregation
the possibility
the miniature
has resulted
in
and
tem
its limited
reexamine
be repeated
to
the antibody
is of
The lack of specificity
both
for
cipitate
transfusion.
It may be expected
that an antibody with this epitopic
specificity
may exert
its predominant
effect on in vivo survival
rather
than factor
VIII:C
coagulant
function.
The
practical
expression.
This
that possibility.
species
and
porcine
specificity
basic interest.
factor
have
rhage
mating
otherwise
in one
of
VlIl:C
allowed
been
animal.
a fatal
This
will
us to treat
experience
using
this preparation.’5
quently
able to confirm
the efficacy
V I I I concentrate
in more adequately
using
the CBT
model
previously
These
data
suggest
thecanine/anti-canine
what
would
intnaabdominal
is in line with
VIII
levels
with
in the canine/anti-canine
association
of detectable
negligible
recovery
subsefactor
studies
In
the
clinical
inhibitors,
described.7
that the epitope
recognized
by
factor
VIll:C
antibody
is either
not present
on is protected
in the porcine
factor
VIII:C
molecule.
Our present
data do not allow us to come to
any firm conclusions
with regard
to the canine
anti-
following
management
of
has
been suggested
response
is an
future
management.’5
it
an anamnestic
prognosis
for
hemophiliacs
support
to anecdotal
clinical
reports
necessarily
the case.’9
Results
from
previous
studies
employing
the
that clinical
response
is closely
development
canine
antibody
in animals
deficiency
closely
mimics
with
many
will be required
disease
with
studies
should
Gawryl
and
coworkers
have recently
demonstrated
that type II (Biggs classification)
anti-factor
VIII:C
antibodies
appear
to necognize an epitope
on
factor
VIII:C
at, on close
to, its
binding
site to factor
VIIIR:Ag/von
Willebrand
facton.’6 We have not yet performed
tion studies
of the canine/anti-canine
antibodies,
preparations
in progress.
similar
due to the requirement
ofcanine
factor
VIII:C.
Factor
VIIIR:Ag/von
this
that
this is not
both
this and
of canine/anti-
classical
features
complication.
allow
with
CBT support
the view
related
to postinfusion
recovery
of factor
VlII:C.7
We conclude
that the
this.
cryopre-
that failure
to mount
indicator
of a good
Our results
lend
porcine
factor
VIII:C
antibody
resulting
from
the
infusion
of the porcine
factor
VIII concentrate.
Our
impression
is that it is recognizing
a different
epitope
with different
functional
properties,
but further
studies
to confirm
sysfactor
Of additional
interest
was the absence
of an anamnestic
antibody
response
in the face of negligible
factor
VlIl:C
recovery
following
the infusion
of canine
cryoprecipitate
in one animal
with a low titer antibody.
hemorclinical
We were
of porcine
controlled
coworkers’
findings
could explain
the
factor
of the
VIII:C
human
Consequently,
us to both
further
investigate
the
patho-
genetic
mechanisms
involved
and to derive
information
that may be used to more
effectively
manage
hemophiliacs
with this difficult
complication.
characterizafactor
VIII:C
ACKNOWLEDGMENT
for
relatively
pure
Such studies
are
Willebrand
factor
We
should
porcine
like
factor
to thank
VIII
illustrations:
and
Speywood
free
Laboratories
Stan
of charge;
Kathy
Fluhrer
for the
Morton
for typing
the
for
supply
of
drawing
the
manuscript.
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1984 63: 451-456
Development of factor VIII:C antibodies in dogs with hemophilia A (factor
VIII:C deficiency)
AR Giles, S Tinlin, H Hoogendoorn, P Greenwood and R Greenwood
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