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Methods for the Measurement of Platelet Function

Alan D. Michelson, MD
This article discusses the advantages and disadvantages of methods for the measure-
ment of platelet function. The focus is on tests that can be used to monitor antiplatelet
activity in the setting of cardiovascular disease and potentially predict thrombosis
and bleeding. The tests described are platelet aggregometry; impedance aggregom-
etry; VerifyNow (Accumetrics, San Diego, CA); Plateletworks (Helena Laboratories,
Beaumont, TX); platelet surface P-selectin, platelet surfaceactivated glycoprotein
IIb/IIIa, and leukocyteplatelet aggregates; TEG Platelet Mapping system (Haemo-
scope, Niles, IL); Impact cone and plate(let) analyzer (DiaMed, Cressier, Switzerland);
Platelet Function Analyzer-100 (Siemens Healthcare Diagnostics, Inc., Deerfield, IL);
phosphorylation of vasodilator-stimulated phosphoprotein; serum thromboxane B2; and
urinary 11-dehydro thromboxane B2. Some of the factors that differentiate these tests are
sample volume requirements, the use of whole blood, the presence of shear, point-of-care
status, need for a technician, and expense. 2009 Published by Elsevier Inc. (Am J
Cardiol 2009;103[suppl]:20A26A)

Platelets circulate in a resting discoid form (Figure 1, lower bosis and bleeding. Methods for the measurement of platelet
left).1 Platelet activation results in the formation of filopodia function in patients are summarized in Table 1.7
and lamellipodia (Figure 1, lower middle), and then platelet
aggregation (Figure 1, upper right). The goal of antiplatelet
drug therapy is to prevent or reverse this process. Specific Platelet Function Assays
The mechanisms of action of antiplatelet drugs are well Platelet aggregometry: Turbidimetric platelet aggre-
known. Aspirin irreversibly acetylates serine 529 of cyclo- gometry in platelet-rich plasma was originally described
oxygenase1 (COX-1), resulting in inhibition of the generation of by Gustav Born8 and John OBrien.9 The end point of this
thromboxane A2 from platelets.2 However, aspirin may have assay is the change in light transmission as a result of
other mechanisms of action, such as via acetylation of fibrin- integrin IIb3 (GP IIb/IIIa) dependent platelet-to-platelet
ogen, von Willebrand factor, and other molecules.3 Thieno- aggregation in response to an agonist.10 The main advan-
pyridines (including ticlopidine and clopidogrel) irreversibly tage of platelet aggregometry is that it is the historical
inhibit platelet P2Y12 adenosine diphosphate (ADP) recep- gold standard, although Born and OBrien designed the
tors,4 and glycoprotein (GP) IIb/IIIa antagonists (including test as a measure of defective platelet function, not as a
abciximab, eptifibatide and tirofiban) inhibit the final common predictor of thrombosis. The disadvantages of platelet
pathway of platelet-to-platelet aggregation.5 aggregometry are that platelet-rich plasma needs to be
Tests of platelet function attempt to measure the point in the prepared, the test is time consuming, and a high sample
activation process reached by the platelets of an individual volume is required.
patient. Possible reasons for measuring platelet function in
patients include screening, diagnosis, monitoring antiplatelet Impedance aggregometry: Platelet aggregation can be
therapy, monitoring prohemostatic therapy, predicting throm- measured in anticoagulated whole blood by the use of im-
bosis, predicting bleeding, and assessing stored platelets.6 pedance rather than turbidimetry.6,10 Impedance is the same
This article discusses methods for the measurement of method that is used in a Coulter counter. Although imped-
platelet function and describes their advantages and disad- ance aggregometry and turbidimetric aggregometry are con-
vantages. The discussion focuses on platelet function tests ceptually measuring the same thingintegrin IIb3 (GP
that can be used in the setting of cardiovascular diseases to IIb/IIIa) dependent platelet-to-platelet aggregationthe
monitor antiplatelet therapy and potentially predict throm- size of the platelet aggregates measured by impedance ag-
gregometry is smaller than that of the platelet aggregates
measured by turbidimetric aggregometry. The major advan-
Center for Platelet Function Studies, University of Massachusetts Med- tage of impedance aggregometry is that it is more physio-
ical School, Worcester, Massachusetts, USA. logic, in that it is a whole blood assay that does not require
Statement of author disclosure: Please see the Author Disclosures the separation of platelet-rich plasma. However, impedance
section at the end of this article. aggregometry still requires a fairly high sample volume, and
Address for reprints: Alan D. Michelson, MD, Center for Platelet
Function Studies, University of Massachusetts Medical School, 55 Lake the assay is still time consuming and expensive because a
Avenue North, Worcester, Massachusetts 01655. technician needs to monitor the agonist-induced aggregation
E-mail address: michelsa@ummhc.org. over a number of minutes.

0002-9149/09/$ see front matter 2009 Published by Elsevier Inc. www.AJConline.org


doi:10.1016/j.amjcard.2008.11.019
Michelson/Methods for the Measurement of Platelet Function 21A

Figure 1. Platelet shape change and aggregation. Scanning electron micrograph of resting (lower left), partially activated (lower middle), and fully activated
platelets (upper right), showing the accompanying shape changes, formation of filopodia and lamellipodia, and platelet aggregation. (Image provided courtesy
of John W. Weisel, Chandrasekaran Nagaswami, and Rustem I. Litvinov, Department of Cell and Developmental Biology, University of Pennsylvania School
of Medicine, Philadelphia, Pennsylvania.) (Reprinted with permission from Elsevier/Academic Press.)1

VerifyNow: VerifyNow (Accumetrics, San Diego, CA), platelet surface, but it is in a resting conformation. With
formerly known as the Ultegra rapid platelet function ana- platelet activation, the conformation of the integrin IIb3
lyzer, is a point-of-care device that, as with turbidimetric changes, and a specific monoclonal antibody, PAC-1, only
aggregation and impedance aggregation, is based on inte- binds to integrin IIb3 when it is in this activated confor-
grin IIb3 (GP IIb/IIIa) dependent platelet aggregation.11 mation.13 Thus, a PAC-1negative platelet is a resting plate-
However, platelet aggregation is augmented by the presence let, and a PAC-1positive platelet is an activated platelet.
of fibrinogen-coated beads (Figure 2).11 Dissimilar to turbi- When platelets are activated, they degranulate, and P-selec-
dimetric aggregation, but similar to impedance aggregation, tinwhich is normally present on the -granule membrane,
the VerifyNow assay is performed in anticoagulated whole not the platelet plasma membrane becomes exteriorized on
blood. Other advantages of the VerifyNow assay are that it is the platelet surface.14 Thus, a P-selectinnegative platelet is a
simple and rapidly performed and requires only a small sample resting platelet, and a P-selectinpositive platelet is an acti-
volume. Furthermore, it is a true point-of-care device in that no vated platelet. In addition, P-selectinpositive platelets very
pipetting is required. Although the VerifyNow assay has a rapidly bind to leukocytes via their constitutively expressed
limited hematocrit and platelet count range, this applies to counter receptor, P-selectin GP ligand 1.14,15 Therefore, cir-
many tests of platelet function. culating leukocyteplatelet aggregates (especially mono-
Plateletworks: Plateletworks (Helena Laboratories, cyteplatelet aggregates) are a more sensitive marker of in
Beaumont, TX) is another device that is based on integrin vivo platelet activation than are circulating P-selectinpos-
IIb3 (GP IIb/IIIa) dependent platelet aggregation.6 It is a itive platelets.15
conceptually simple method in which the platelet count is The advantages of the flow cytometric measurement of
compared in samples with and without agonists. Minimal platelet function by platelet surface P-selectin, activated inte-
sample preparation is required, and it is a whole blood grin IIb3, and/or leukocyteplatelet aggregates are that
assay. The main disadvantage of Plateletworks is that it is these assays require a very low sample volume, and they are
not well studied. whole blood assays. Furthermore, these assays have been stan-
dardized such that fixed samples can be mailed to a core
Platelet surface P-selectin, platelet surfaceactivated laboratory; this is particularly useful in multicenter clinical
GP IIb/IIIa, and leukocyte-platelet aggregates: Platelet trials.16 The disadvantages of these assays are that sample
surface P-selectin, activated integrin IIb3 (GP IIb/IIIa), preparation is required, and they require an expensive machine
and leukocyteplatelet aggregates can be measured by flow (a flow cytometer) and an experienced technician. These as-
cytometry.12 Integrin IIb3 is normally present on the says are therefore currently mainly research tools.
22A The American Journal of Cardiology (www.AJConline.org) Vol 103 (3A) February 2, 2009

Table 1
Methods for the measurement of platelet function in patients
Test Basis Advantages Disadvantages

Turbidimetric aggregometry Platelet aggregation Historical gold standard High sample volume
Sample preparation
Time consuming
Impedance aggregometry Platelet aggregation Whole blood assay High sample volume
Sample preparation
Time consuming
VerifyNow* Platelet aggregation Simple, rapid Limited hematocrit and
Point-of-care (no pipetting required) platelet count range
Low sample volume
Whole blood assay
Plateletworks Platelet aggregation Minimal sample prep Not well studied
Whole blood assay
Platelet surface P-selectin, Activation-dependent changes in Low sample volume Sample preparation
platelet surface-activated GP platelet surface Whole blood assays Requires a flow cytometer and
IIb/IIIa, leukocyte-platelet Fixed samples can be mailed to a core experienced technician
aggregates laboratory
TEG Platelet Mapping system Platelet contribution to clot strength Whole blood assay Limited studies
Clot information Requires pipetting
Impact cone and plate(let) Shear-induced platelet adhesion Simple, rapid Requires pipetting
analyzer Point of care Instrument not widely used
Low sample volume
No sample prep
Whole blood assay
Shear
PFA-100 In vitro cessation of high shear Simple, rapid Dependent on von Willebrand
blood flow by platelet plug Point-of-care factor and hematocrit
Low sample volume Requires pipetting
No sample prep Does not correlate well with
Whole blood assay clopidogrel therapy
Shear
VASP Activation-dependent signaling Dependent on clopidogrel target, Sample preparation
P2Y12 Requires a flow cytometer and
Low sample volume experienced technician
Whole blood assay
Blood samples can be mailed at room
temperature to a core laboratory
Serum thromboxane B2 Activation-dependent release from Directly dependent on aspirins target, Indirect measure
platelets COX-1 Not platelet specific
Urinary 11-dehydro Stable urinary metabolite of Directly dependent on aspirins target, Indirect measure
thromboxane B2 creatinine thromboxane B2 COX-1 Not platelet specific
ratio

COX-1 cyclooxygenase-1; GP glycoprotein; PFA platelet function analyzer; TEG thromboelastography; VASP vasodilator-stimulated
phosphoprotein.
* VerifyNow (Accumetrics, San Diego, CA).

Plateletworks (Helena Laboratories, Beaumont, TX).

TEG Platelet Mapping system (Haemoscope, Niles, IL).

Impact cone and plate(let) analyzer (DiaMed, Cressier, Switzerland).

Platelet Function Analyzer-100 (Siemens Healthcare Diagnostics, Inc., Deerfield, IL).
Modified with permission from Circulation.7

TEG Platelet Mapping system: Although thromboelas- to measure the 2 processes in the 1 assay.18 An additional
tography (TEG) was invented 50 years ago, it has recently advantage of the TEG Platelet Mapping system is that it is
been updated to a more platelet-specific test in the form of a whole blood assay. Its disadvantages are that it is not a
the TEG Platelet Mapping system (Haemoscope, Niles, true point-of-care instrument in that it requires pipetting,
IL).6 The particular advantage of the TEG Platelet Mapping and there are a limited number of published studies involv-
system is that, in addition to measuring platelet function, it ing this assay.18
specifically measures the platelet contribution to clot
strength. Although platelet function and coagulation are Impact cone and plate(let) analyzer: The Impact cone
often considered separately, they are, of course, completely and plate(let) analyzer (DiaMed, Cressier, Switzerland) was
interrelated processes.17 Therefore, it may be advantageous originally developed in Israel by David Varon and Naphtali
Michelson/Methods for the Measurement of Platelet Function 23A

Figure 2. Determination of platelet function with the VerifyNow system (Accumetrics, San Diego, CA). The mixing chamber contains a platelet agonist
(thrombin receptoractivating peptide (TRAP) [iso-TRAP], arachidonic acid, or adenosine diphosphate [ADP]) and fibrinogen-coated beads. After antico-
agulated whole blood is added to the mixing chamber, the platelets become activated. The activated glycoprotein (GP) IIb/IIIa receptors on the platelets bind
via the fibrinogen on the beads and cause agglutination of the platelets and the beads. Light transmittance through the chamber is measured and increases
as the agglutinated platelets and beads fall out of solution. Direct pharmacologic blockade of GP IIb/IIIa receptors with a GP IIb/IIIa antagonist or the
prevention of their expression by the inhibition of arachidonic acidinduced or ADP-induced platelet activation diminishes agglutination in proportion to the
degree of platelet inhibition achieved. (Reprinted with permission from Elsevier/Academic Press.11)

Savion. The end point of this assay is shear-induced platelet the PFA-100 are that the closure time is very dependent on von
adhesion. This is potentially quite advantageous because Willebrand factor levels and hematocrit. Although initial pipetting
shear is very important for platelet function,19 particularly in of the blood sample is necessary, the sample is simply inserted
the setting of coronary artery disease (CAD).20 Although into a cassette, a button is pressed, and a rapid readout is obtained.
turbidimetric aggregometry and impedance aggregometry The PFA-100 has 2 available cartridges: a collagen epineph-
are performed in stirred samples, the shear rate in these rine cartridge and a collagenADP cartridge. The PFA-100
assays is an order of magnitude below the shear rate that is has been widely used to study aspirin response.6,23 Surpris-
relevant to CAD. The research version of the Impact ana- ingly, the PFA-100, even with the collagenADP cartridge,
lyzer has an adjustable shear rate, and, in the clinical ver- is not sensitive to clopidogrel therapy.
sion, the shear rate is directly relevant to that in CAD.21
Phosphorylation of vasodilator-stimulated phospho-
Additional advantages of the Impact are simplicity, rapid
protein: Phosphorylation of vasodilator-stimulated phos-
readout, low sample volume, no sample preparation, and the
phoprotein (VASP) for the measurement of P2Y12 antago-
fact that it is a whole blood assay. The disadvantages of the
nism is available commercially as a flow cytometry kit
Impact are that it is not a true point-of-care instrument
(BioCytex, Marseilles, France).12 Prostaglandin E1 binds to
because it requires pipetting. Additionally, although there
its inositol phosphate receptor on the platelet surface and
are a number of published studies describing this assay,21
signals through a G stimulatory protein and adenylyl cy-
the instrument is not widely used.
clase to convert adenosine triphosphate to cyclic adenosine
Platelet Function Analyzer-100: The Platelet Function monophosphate and then, through protein kinase A, to con-
Analyzer100 (PFA-100; Siemens Healthcare Diagnostics, vert VASP to phosphorylated VASP (VASP-P) (Figure 3).24
Inc., Deerfield, IL) also has the advantage of including a ADP binds to its P2Y12 receptor on the platelet surface and
physiologically relevant shear rate.22 This device has been signals through a G inhibitory protein to inhibit prostaglan-
referred to as an in vitro bleeding time (not an ideal term), din E1induced signaling through adenylyl cyclase. P2Y12
but the concept is that of an in vitro method for looking at antagonists (for example, the active metabolite of clopi-
cessation of blood flow in a high-shear environment, as dogrel) inhibit this ADP-induced effect. Therefore, in the
determined by the closure time of an aperture by the for- presence of both prostaglandin E1 and ADP, VASP-P is
mation of a platelet plug. In addition to shear, the advan- directly proportional to the degree of P2Y12 antagonism
tages of the PFA-100 are its simplicity, rapid readout, low (Figure 3). VASP-P is measured by whole blood flow cy-
sample volume, no requirement for sample preparation, and tometry, using permeabilization and a monoclonal antibody
the fact that it is a whole blood assay. The disadvantages of specific for the phosphorylated form of VASP.
24A The American Journal of Cardiology (www.AJConline.org) Vol 103 (3A) February 2, 2009

Table 2
Platelet function tests for monitoring aspirin
Thromboxane as the end point
Serum thromboxane B2
Urinary 11-dehydro thromboxane B2
Arachidonic acid as the stimulus
Platelet aggregometry (turbidimetric)
Platelet aggregometry (impedance)
VerifyNow* aspirin assay
Plateletworks
Platelet surface-activated glycoprotein IIb/IIIa, platelet surface
P-selectin, leukocyte-platelet aggregates (flow cytometry)
TEG Platelet Mapping system
Impact cone and plate(let) analyzer
Other
Platelet Function Analyzer100

* VerifyNow (Accumetrics, San Diego, CA).



Plateletworks (Helena Laboratories, Beaumont, TX).

TEG Platelet Mapping system (Haemoscope, Niles, IL).

Impact cone and plate(let) analyzer (DiaMed, Cressier, Switzerland).

Platelet Function Analyzer-100 (Siemens Healthcare Diagnostics, Inc.,
Deerfield, IL).
Adapted with permission from Eur Heart J.28

and it may not be entirely platelet specific.26 The potential


effects of renal function are obviated by measuring the ratio
of urinary 11-dehydro thromboxane B2 to creatinine.27
Figure 3. Vasodilator-stimulated phosphoprotein (VASP) assay for the
measurement of P2Y12 antagonism. AC adenylyl cyclase; ADP
adenosine diphosphate; ATP adenosine triphosphate; cAMP cyclic
adenosine monophosphate; PGE1 prostaglandin E1; PKA protein
Approach to Monitoring Antiplatelet Therapy
kinase A; VASP-P phosphorylated vasodilator-stimulated phosphopro- Platelet function tests for monitoring aspirin: Consid-
tein. (Adapted with permission from Elsevier/Academic Press.24) ering this cornucopia of available platelet function tests,
how should the effects of aspirin be monitored? There are 3
categories of available tests (Table 2).28
The advantages of the VASP assay are that it is depen- First, thromboxane could be used as the end point, with
dent on the target of clopidogrel (P2Y12), and it involves an assay of either serum thromboxane B2 or urinary 11-
low sample volume and whole blood assays. In addition, dehydro thromboxane B2. The advantage of this approach is
quite remarkably, citrated blood samples can be mailed at that aspirin specifically inhibits platelet COX-1 and, there-
room temperature to a core laboratory; this is particularly fore, thromboxane generation. A possible disadvantage is
useful in multicenter clinical trials.16 The disadvantages of that nearly all patients who are compliant with taking aspi-
the VASP assay are sample preparation and the requirement rin are inhibited as judged by serum thromboxane B2 or
for a flow cytometer and an experienced technician. urinary 11-dehydro thromboxane B2 assays but not neces-
sarily as judged by other assays.3,29
Serum thromboxane B2: Thromboxane A2 is released
Second, arachidonic acid can be used as the stimulus.
from platelets in an activation-dependent manner, after
The advantage of this approach is that arachidonic acid
which it is rapidly converted to its stable metabolite, throm-
results in specific signaling through COX-1, the point of
boxane B2.25 The advantage of measuring serum thrombox-
inhibition by aspirin. Again, the assumption is that all of the
ane B2 is that it is directly dependent on aspirins target,
effects of aspirin result from its inhibition of COX-1, which
COX-1. The disadvantages of measuring serum thrombox-
might not be entirely true.3,29 With arachidonic acid as the
ane B2 are that it is an indirect measure in the sense that
stimulus, one of a number of end points could be chosen,
platelets are not directly assayed, and it may not be entirely
including turbidimetric platelet aggregometry, impedance
platelet specific.26
platelet aggregometry, the VerifyNow aspirin assay,
Urinary 11-dehydro thromboxane B2: Urinary 11-de- Plateletworks, platelet surfaceactivated GP IIb/IIIa, plate-
hydro thromboxane B2 is a stable urinary metabolite of let surface P-selectin, leukocyteplatelet aggregates, the
thromboxane A2.25 The advantage of measuring urinary TEG Platelet Mapping system, and the Impact cone and
11-dehydro thromboxane B2 is that it is directly dependent plate(let) analyzer. However, older studies of the Veri-
on aspirins target, COX-1. The disadvantages of measuring fyNow (Ultegra rapid platelet function analyzer), including
urinary 11-dehydro thromboxane B2 are that it is an indirect the widely quoted study by Chen et al,30 used propyl gallate,
measure in the sense that platelets are not directly assayed, not arachidonic acid, as the stimulus.
Michelson/Methods for the Measurement of Platelet Function 25A

Table 3 turbidimetric platelet aggregometry, impedance platelet ag-


Platelet function tests for monitoring clopidogrel gregometry, the VerifyNow P2Y12 assay, Plateletworks,
P2Y12-specific tests platelet surfaceactivated GP IIb/IIIa, platelet surface P-
VASP phosphorylation (flow cytometry) selectin, leukocyteplatelet aggregates, the TEG Platelet
ADP-stimulated tests
Mapping system, and the Impact cone and plate(let)
Platelet aggregometry (turbidimetric)
Platelet aggregometry (impedance) analyzer.
VerifyNow* P2Y12 assay
Plateletworks Platelet function tests for monitoring GP IIb/IIIa
Platelet surfaceactivated GP IIb/IIIa, platelet surface P-selectin, antagonists: GP IIb/IIIa antagonists can be monitored by 2
leukocyte-platelet aggregates (flow cytometry)
categories of tests (Table 4). First, because GP IIb/IIIa antag-
TEG Platelet Mapping system
Impact cone and plate(let) analyzer onists block the final common pathway of platelet aggrega-
tion,5 inhibition of platelet aggregation can be assessed by one
ADP adenosine diphosphate; GP glycoprotein; TEG throm- of a number of end points: turbidimetric platelet aggregometry,
boelastography; VASP vasodilator-stimulated phosphoprotein.
* VerifyNow (Accumetrics, San Diego, CA). impedance aggregometry, VerifyNow thrombin receptoracti-

Plateletworks (Helena Laboratories, Beaumont, TX). vating peptide assay, or Plateletworks. Second, because plate-

TEG Platelet Mapping system (Haemoscope, Niles, IL). let aggregation cannot occur without a conformational change
in integrin IIb3 (GP IIb/IIIa), flow cytometry can be used to

Impact cone and plate(let) analyzer (DiaMed, Cressier, Switzerland).
Adapted with permission from Eur Heart J.28 measure a conformational change in platelet surfaceactivated
GP IIb/IIIa reported by monoclonal antibody PAC-112,13 or a
Table 4 ligand-induced binding site.32,33
Platelet function tests for monitoring glycoprotein (GP) IIb/IIIa
antagonists
Platelet aggregation
Platelet aggregometry (turbidimetric) Point-of-Care Assays
Platelet aggregometry (impedance)
VerifyNow* TRAP assay Point-of-care assays (also referred to as point-of-service
Plateletworks
Activation-dependent conformational change in GP IIb/IIIa by flow
assays) have potentially great advantages. For example,
cytometry they help with immediate decision making about the type
Platelet surfaceactivated GP IIb/IIIa (PAC-1) and dose of antiplatelet therapy in the interventional cardi-
Ligand-induced binding site ology suite. A rigorous definition of a point-of-care assay is
TRAP thrombin receptor-activating peptide. an assay that meets all of the following criteria: use at or
* VerifyNow (Accumetrics, San Diego, CA). near the patient bedside; easy to use, requiring no special

Plateletworks (Helena Laboratories, Beaumont, TX). skills; no sample processing; no pipetting; rapid readout.
The only currently available device that fits these criteria is
VerifyNow.11 However, 2 other devices are in develop-
Third, the PFA-100 has been widely used to study the ment: T-Guide (ThromboVision, Houston, TX), based on
response of platelets to aspirin.31 Unlike the first 2 catego- agonist-induced laser light scattering; and PRT (PlaCor,
ries in Table 2, the PFA-100 is not COX-1 specific. Is that Plymouth, MN), based on a finger stick capillary blood
a disadvantage or could it be an advantage if aspirin also has sample with no exogenously added agonist.
nonCOX-1mediated inhibitory effects3,29 on platelets?

Platelet function tests for monitoring clopidogrel:


How should the effects of clopidogrel be monitored? There Conclusion
are 2 categories of available tests (Table 3).28 First, only the
VASP phosphorylation assay is specific with regard to sig- A wide variety of tests are available for the measurement of
naling through P2Y12 and therefore to the platelet inhibitory platelet function, and each has its advantages and disadvan-
effects of clopidogrel (Figure 3). Second, ADP can be used tages. The most specific tests for the effect of aspirin are
as the stimulus. The alternative approach is to add ADP and directly dependent on COX-1 (ie, the measurement of
look at one of a number of end points. However, it is thromboxane or the use of arachidonic acid as a stimulus).
important to consider that ADP binds to its platelet surface However, it remains unclear whether the measurement of
P2Y1 receptor as well as to its platelet surface P2Y12 re- the potential nonCOX-1 effects of aspirin may also be
ceptor24 and that the active metabolite of clopidogrel only important to measure. The most specific test for the effect of
inhibits at P2Y12, not P2Y1.4 Therefore, the effects of ADP clopidogrel is the VASP phosphorylation assay. Point-of-
on platelet function reflect not only the inhibitory effects of care assays for the measurement of the effects of aspirin and
clopidogrel on P2Y12 but also the unblocked effect of ADP- clopidogrel (eg, VerifyNow Aspirin Assay and VerifyNow
induced signaling through P2Y1. With ADP as the stimulus, P2Y12 Assay) have great practical advantages in the clinical
one of a number of end points could be chosen, including setting.
26A The American Journal of Cardiology (www.AJConline.org) Vol 103 (3A) February 2, 2009

Author Disclosure pared with high loading- and maintenance-dose clopidogrel in patients
with planned percutaneous coronary intervention: the Prasugrel in
Comparison to Clopidogrel for Inhibition of Platelet Activation and
The author who contributed to this article has disclosed the
Aggregation-Thrombolysis in Myocardial Infarction 44 trial.
following industry relationships. Circulation 2007;116:29232932.
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