Principles,
Indications, and Limitations of the Platelet
Function Analyzer
Christopher J. Stasik, DO
Coagulation Resource Committee
In the past, screening for primary hemostatic
disorders, particularly von
Willebrand disease (vWD), was performed using the
manual bleeding time
method. Bleeding time testing has been criticized
for being invasive, poorly
reproducible and insensitive. Screening tests with a
higher sensitivity for platelet
dysfunction and von Willebrand disease (vWD) have
been unavailable until now.
The introduction of the automated platelet function
analyzer (PFA-100â, Dade
Behring, Deerfield, Illinois) has provided an
alternative to the manual bleeding
time method with increased sensitivity for platelet
dysfunction, particularly with
regard to vWD.
The coagulation cascade in vivo is stimulated by
vessel wall injury and continues
toward the formation of a platelet plug under the
influence of various stimulators
of platelet adhesion and aggregation. Well-known
stimulators of this process
include epinephrine, adenosine diphosphate (ADP),
collagen, thrombin and
thromboxane A2. The PFA-100 simulates the conditions
following vascular wall
injury. Whole blood (citrate anticoagulated) is
aspirated from a reservoir through
a capillary and a biologically active membrane. The
membrane, coated with
either collagen/epinephrine or collagen/ADP,
contains a central aperture
(simulating vessel wall injury). As blood flows
through the aperture, platelets
begin to adhere and aggregate. The time until the
aperture is completely
occluded by the platelet/red blood cell thrombus is
termed the “closure time.”
It has been shown that the PFA-100 is more
sensitive for screening patients for
vWD (except type 2N) than the manual bleeding time.1
Since the closure time
has been shown to fully correct following
desmopressin acetate (DDAVPâ)
treatment, the PFA-100 may also be used for
therapeutic monitoring of treated
vWD.1 Abnormal closure times may be seen in various
other platelet disorders,
however sensitivity and specificity are not high
enough to justify use of the PFA-
100 as a routine screening tool in these cases.2 The
closure time in congenital
platelet disorders varies depending on the severity
of the disease. Severe forms,
such as Glanzmann thrombasthenia, Bernard-Soulier
syndrome and platelet-type
vWD, result in a markedly prolonged closure time. It
is currently recommended
that platelet aggregation studies be performed in
addition to the PFA-100 for a
thorough evaluation of platelet function.
While a normal PFA-100 closure time effectively
rules out moderate to severe
vWD, mild type 1 vWD may not impact the closure time
and further testing with
ristocetin cofactor activity and von Willebrand
factor antigen should be carried out
when clinical suspicion is high.3 Prolongation of
the closure time must be
evaluated within the appropriate clinical context.
Thrombocytopenia (platelet
count below 150,000/uL) and a decreased hematocrit
(<35%) may prolong the
closure time because formation of a platelet/red
cell thrombus is directly
dependent upon these factors. Test results with both
the collagen/epinephrine
and the collagen/ADP membranes should be prolonged
in vWD; however,
isolated closure time prolongation with the
collagen/epinephrine cartridge occurs
in patients taking aspirin. Clopidogrel (Plavixâ)
and ticlopidine (Ticlidâ) do not
cause an abnormal PFA-100 result. Bleeding due to
coagulation factor
deficiencies cannot be detected using the PFA-100.
In summary, the PFA-100 is a more sensitive
screening test than the manual
bleeding time for the diagnosis of von Willebrand
disease (types 1, 2A, 2B, and
3) and may be useful for other specific platelet
function disorders. The test uses
stimulators of platelet aggregation and adhesion in
an environment that simulates
an injured blood vessel wall. The time until
complete occlusion of blood flow
through an aperture (closure time) is the measured
end point. In addition to vWD
screening, the PFA-100 is also indicated for
monitoring treatment efficacy of
DDAVP in vWD patients. False-positive closure time
prolongation may be seen
with thrombocytopenia (<150,000/uL) or a low
hematocrit (<35%). Aspirin
therapy will prolong the closure time with the
collagen/epinephrine cartridge, a
feature that allows the PFA-100 to be used as a
screen for coagulopathy due to
aspirin effects. Coagulation factor defects or the
use of Ticlid and Plavix, do not
prolong the closure time. Thorough evaluation of
platelet dysfunction should
include platelet aggregation studies in addition to
the PFA-100.
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