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Interventional Cardiology
agonist peptide (TRAP) as agonist (sensitive to GPIIb/IIIa antagonists); (VASP-P) has become available.
85
VASP-P is modulated by the cyclic
aspirin assay with AA as agonist (sensitive to aspirin); and P2Y12 adenosine monophosphate (cAMP) cascade activated by PGE1, whereas
assay with ADP as agonist (sensitive to thienopyridines) and it is inhibited by ADP through P2Y12 receptors. In this assay, incubation of
prostaglandin E 1 (PGE 1) as a suppressor of intracellular free calcium a blood sample with PGE1 with and without ADP is previously achieved.
levels to reduce the non-specific contribution of the ADP-binding VASP-P, identified by a specific monoclonal antibody, is indirectly labelled
P2Y1 receptors. and analyzed. So, VASP-P is directly proportional to the level of activation
of the platelet P2Y12 receptor, which is blocked by thienopyridines.
20,86
For aspirin assay, results are expressed as aspirin reaction units (ARU),
and for the identification of responsiveness to ASA treatment a specific The advantages of this method are that it is dependent on the P2Y12
cut-off value of 550ARU is recommended by manufacturers. This value receptor target of clopidogrel and uses low whole blood samples;
was chosen by Malinin et al.,
71
who reported a significant correlation drawbacks are that it is expensive and requires sample preparation,
between this method and EPI-induced LTA. In addition, various studies skilled technicians and the availability of a flow cytometer. Aleil et al.
85
compared this method with AA-LTA and PFA-100 CEPI CT. In stroke demonstrated that the VASP assay finds a higher inhibition by
patients on low doses of ASA
43,44
and coronary artery disease patients thienopyridine compared with LTA, probably because LTA still takes
on dual antiplatelet therapy,
34,41,52,72
a moderate agreement was place via ADP stimulation of P2Y1 in the presence of thienopyridine.
observed. Recent studies have pointed out that this method may be Adjustment of the clopidogrel loading dose according to this method
used to monitor differences in ASA concentration and preparation.
73
may improve the clinical outcome after PCI in patients who are non-
Dichiara et al.
74
correlated the ASA assay with different platelet function responsive to clopidogrel.
87
tests, demonstrating that this method is able to distinguish a
generalized high platelet reactivity. Furthermore, studies that may Plateletworks
relate RPR revealed by this assay with adverse clinical outcomes must Plateletworks (Helena Laboratories, US) is a POC whole-blood test
be still performed, so this method may be suitable to monitor and, in constituting an aggregation kit and an Ichor blood counter. The
time, to change ASA therapy. aggregation test is based on measuring the platelet count before and
after inducing platelet aggregation, using as agonists collagen, ADP, or
For the VerifyNow P2Y12 assay, results are expressed as P2Y12 reaction AA, consisting of a baseline tube and an agonist reagent tube (citrate
units (PRU). Recent small comparisons with ADP-induced LTA have been tube plus agonist).
88
Platelet aggregation is measured as the loss of
performed reporting significant relationships between methods.
75,76
An single platelets. Results are available in minutes and without any
initial report has validated this method for evaluating inhibition by manipulation of a blood sample. This assay correlates with LTA, IPA,
clopidogrel with a precision of 8%.
77
A study on a large group of ACS TEG, and VerifyNow,
89,90
and may be used to monitor antiplatelet
patients on clopidogrel performed in our department has tried to choose a therapy.
53,92
However, it is still under consideration and has not
cut-off value—244PRU—to definite RPR showing a high concordance and reported clinical outcomes.
high specificity of this method in relation to ADP plus LTA.
20
Recently, Price
et al.,
78
who chose a cut-off value of 235PRU (similar to that of our study), IMPACT Cone and Plate Technology Cone and
demonstrated that high platelet reactivity measured with the P2Y12 assay Plate(let) Analyzer
is associated with post-discharge events after PCI with drug-eluting stents Image Analysis Monitoring Platelet Adhesion Cone and Plate
(DES), including stent thrombosis. Technology (IMPACT) Cone and Plate(let) Analyzer (CPA) (Diamed,
Switzerland) is a new POC fully automated system that measures
Thrombelastography platelet adhesion and aggregation under high shear stress conditions
Thromboelastography/thromboelastometry (TEG) is now used as a bedside simulating in vitro primary hemostasis.
1,5,6,93
Whole blood is exposed to
monitor in cardiac or hepatic surgery.
79
In a rotating system comprising a shear stress by the spinning of a cone in a standardized polystyrene
pin suspended by a torsion wire in a cup, blood clotting entraps the pin, plate. After automated staining, the percentage of the well surface
promoting motion that increases as the clot strengthens and decreases as covered by platelet aggregates—representing platelet adhesion—and
the clot lyses. A thrombelastograph platelet-mapping system (Hemoscope, the average size of the aggregates (per µm
2
) are measured by image
US) has been developed to monitor antiplatelet therapy.
80–82
A weak clot is analysis software. The addition of AA and ADP ex vivo allows us to
formed by the addition of reptilase and factor XIII. By adding AA or ADP, the evaluate dual antiplatelet therapy.
94,95
This system still needs an
clot strength is increased, allowing this assay to be sensitive to dual experienced user, and additional studies must be performed to
antiplatelet therapy. This system provides a global POC test of hemostasis establish its possible role in monitoring antiplatelet therapy.
that can not only identify low responsiveness to ASA and/or clopidogrel
but also give information on clot formation and lysis.
82–84
However, studies Conclusions
on a large sample size should be performed to determine its possible role Many platelet function tests are now available for clinical use,
in monitoring antiplatelet therapy. including monitoring antiplatelet therapy, and some of these tests
have been shown to be associated with clinical outcomes in patients
Vasodilator-stimulated Phosphoprotein on dual antiplatelet therapy. In ACS patients, who present a high
Phospholorylation State variability of the response, the ultimate goal of these tests is to guide
Recently, a standardized flow cytometric assay based on the finding antiplatelet therapy to the optimal dosage for the prevention or
of a phosphorylated form of vasodilator-stimulated phosphoprotein treatment of thrombosis by minimizing side effects. The development
78 US CARDIOLOGY
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