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Serological features of antibodies to protamine inducing thrombocytopenia and thrombosis.
[heparin-induced thrombocytopenia]
Abstract
Background
:
A
significant
proportion
of
patients
undergoing
cardiopulmonary
bypass
develop
anti-protamine
antibodies
,
with
or
without
the
association
of
thromboembolic
events
.
Methods
:
We
extensively
investigated
the
serological
features
of
protamine
antibodies
,
which
developed
in
six
patients
who
were
clinically
suspected
to
have
heparin-induced
thrombocytopenia
(
HIT
)
.
Three
patients
had
thrombotic
events
.
Sera
were
tested
by
four
different
commercially
available
immunoassays
,
a
heparin-
platelet
aggregation
test
,
and
for
their
binding
properties
to
heparin
,
platelet
factor
4
(
PF
4
)
,
complex
heparin-
PF
4
,
protamine
,
and
protamine
complex
with
heparin
.
Sera
from
four
patients
were
also
tested
for
the
capability
to
induce
platelet
activation
and
the
formation
of
platelet
-monocyte
heterotypic
aggregates
.
Results
:
The
ELISA
assay
Zymutest
HIA
was
strongly
positive
in
all
cases
,
the
HPIA
Asserachrome
was
borderline
,
and
the
gel
centrifugation
test
PaDGIA
was
positive
in
two
tested
patients
.
Platelet
aggregation
tests
were
negative
.
Using
a
variation
of
the
Zymutest
HIA
we
demonstrate
that
IgG
antibodies
bound
only
to
protamine
or
protamine
complex
with
heparin
,
but
not
to
heparin
or
PF
4
only
.
Sera-induced
platelet
P-
selectin
expression
and
the
formation
of
platelet
-monocyte
aggregates
.
Blood
samples
from
one
patient
proofed
positive
concomitantly
with
the
thromboembolic
event
.
However
,
serological
characteristics
did
not
differ
between
antibodies
associated
with
thromboembolic
events
from
those
without
.
Conclusions
:
These
data
show
that
protamine-induced
antibodies
are
specific
and
may
induce
platelet
activation
,
which
explains
their
association
with
thromboembolic
events
.
Diseases
Validation
Diseases presenting
"platelet-monocyte aggregates"
symptom
heparin-induced thrombocytopenia
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