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Platelet Function Testing in High-risk Coronary Artery Disease Patients—An Update
platelets expose their surface receptors, which allows them to attach adhesion and aggregation in response to shear stress and agonists in
to artificial surfaces.
46,47
IPA measures the change in electrical the membrane forming a platelet plug that occludes the aperture. The
resistance or impedance between two electrodes set at a fixed time taken to occlude the hole is the closure time (CT), a measure of
distance into a blood sample. As the current passes, platelets adhere overall platelet-related hemostasis, and this interval will be elongated
depending on platelet activity. CEPI CT is sensitive to ASA therapy, while
the CADP CT is unaffected by ASA and clopidogrel.
60,61
The use of two
different cartridges with distinct agonists allows us to distinguish
between platelet function alterations due to intrinsic defects (CADP)
Data suggest that a generalized
and those due to therapy with antiplatelet drugs (CEPI). Even if this
persistent platelet reactivity phenotype
method is less specific for ASA monitoring than other assays, PFA-100
has been widely used in clinical studies for identification of ASA
exists that might enhance thrombotic risk.
responsiveness in cardiovascular patients.
62
Several studies have
reported a high prevalence of ASA-resistant patients.
34,60,63
This assay
provides a global assessment of non-vascular primary hemostasis, and
therefore has the advantage of taking different mechanisms for platelet
to electrodes and, in response to classic agonists, other platelets activation into account. It has been demonstrated that different
aggregate around those attached to the electrodes, increasing the determinants, such as high levels of von Willebrand factor (vWF),
electrical impedance. The extent of the increase in impedance is fibrinogen, or erythrocytes, tend to shorten CEPI CT.
64,65
So, the PFA-
recorded in Ohm. The use of whole blood allows platelet function to 100™ CT could potentially serve to detect high RPR despite aspirin
be assessed under more physiological conditions that also take into therapy, and thereby predict the risk for ischemic events.
66–68
In a
account the contributions of other blood elements that may affect comparison study performed in ACS patients, Paniccia et al.
34
reported
platelet function. Another important difference compared with LTA is a high concordance between LTA and PFA-100 CEPI test results,
that IPA takes place on surfaces. In LTA, platelets aggregate with each identifying the same patients with or without RPR. In addition, Marcucci
other in the liquid phase, which presumably happens only in severely et al.
67
demonstrated that RPR revealed by CEPI test is a significant and
ill patients (i.e. heparin-induced thrombocytopenia type II [HIT II] and independent predictor of MACEs in patients with AMI undergoing
disseminated intravascular coagulation [DIC]), whereas physiological primary PCI. In a recent review, Reny et al.
69
reported that in
coagulation and platelet aggregation in vivo usually take place only on cardiovascular patients on ASA RPR measured with CEPI, CT is
surfaces (vascular injuries, inflamed vessels, atheromatous plaques). associated with recurrent ischemic events (with an odds ratio [OR] of
2.1). In addition, in a systematic review of 53 studies Crescente et al.
63
IPA has many advantages, including small sample volume and reported a similar result—notwithstanding the heterogeneity of the
immediate analysis with no sample manipulation, loss of time, or studies analyzed—but concluded that better standardization and
possible failure of subpopulation. Until now, the aggregometers for control of methodological variables for this test might reinforce the
IPA (Chronolog device, US) utilized reusable electrode units, so after observed association with clinical vascular events.
each test the electrodes had to be carefully rinsed and wiped. The
need to clean and ensure the integrity of electrodes made IPA difficult VerifyNow System
to use in clinical practice. Now, a five-channel computerized IPA The VerifyNow system (Accumetrics, US) is a POC turbidimetric-based
device (Multiple Platelet Function Analyzer, Multiplate-Dynabyte, optical detection device that measures platelet aggregation in a
Germany) has become available that has disposable ready-to-use system cartridge containing fibrinogen-coated beads and a specific
cuvettes with two independent sensor units. The increase in
impedance is detected in each sensor unit and calculated as area
under the curve (AUC). As IPA may use different agonists (similar to
Impedance platelet aggregometry has
LTA), it is suitable for both diagnosis and monitoring of antiplatelet
therapy. Now, some partial studies have monitored the effect of
many advantages, including small sample
antiplatelet therapy with either the old aggregometers
48–52
or the
volume and immediate analysis with no
Multiplate,
53–57
but a comparison with LTA including AA, ADP, and
collagen as agonists and the choice of a cut-off value to discriminate
sample manipulation, loss of time, or
patients with or without RPR is necessary.
possible failure of subpopulation.
New Choices for Platelet Function Tests
Platelet Function Analyzer-100 agonist.
70
The instrument measures changes in light transmission, and
The Platelet Function Analyzer-100 (PFA-100) (Dade Behring, US) thus the rate of aggregation in whole blood. The VerifyNow system
assesses platelet function in whole blood, simulating primary allows the rapid assessment of RPR without the requirement of a
hemostasis under shear stress conditions by using proper specialized laboratory because no laboratory instrument handling or
cartridges.
58,59
Blood is aspirated at a high shear stress rate through a blood manipulation is required. This methodology is specific to the
defined aperture cut into a collagen-coated membrane (C) filled with monitoring of antiplatelet therapy, comprising three different assays
either EPI (CEPI cartridge) or ADP (CADP cartridge). Platelets undergo each sensitive to targeted drugs: IIb/IIIa assay with thrombin receptor
US CARDIOLOGY 77
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