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Oral Antiplatelet Therapy After PCI:
Optimizing Outcomes in Clinical Practice
Assessing Platelet Reactivity with
Point-of care Systems
Christian Valina
Herz-Zentrum Bad Krozingen
Assessing Platelet Reactivity with
Point-of care Systems
Platelet-function tests
What kind of POC-tests are available?
Differences in test results
Assessing Platelet Reactivity with
Point-of care Systems
Platelet-function tests
What kind of POC-tests are available?
Differences in test results
Platelet-function tests
Test principle
Tests
Cessation of bleeding from a standardized
wound in vivo
Bleeding time
Aggregometry
Light transmission aggregometry (LTA)
Multiplate® WBA
VerifyNow®
Platelet counting method (e.g. Ichor-plateletworks®)
Thrombovision T® guide
Flow cytometry
Detection of activation markers ex vivo
Ex vivo stimulation and detection of activation markers
VASP phosphorylation
Shear dependent platelet function within whole PFA-100®
blood
IMPACT® -CPA
Placor PRT-7000®
Global haemostasis tests
Thrombelastography (TEG®)
Thrombelastometry (ROTEM®)
Haemostasis Analysis System®
Thromboxane measurements
Serum thromboxane B2
Harrison, Hämostaseologie 2009; 29: 25
Platelet function testing: Some Problems
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No definitive screening test
Methodological variability within each technique
Labor intensive
Costly
Time consuming
Requirement of fair degree of expertise and experience to
perform and interpret
• Often requirement of additional expensive specialist tests
• Lack of a standardized definition of suboptimal platelet
response
Assessing Platelet Reactivity with
Point-of care Systems
Platelet-function tests
What kind of POC-Devices are available?
Differences in test results
Point-of-care-testing: What should they can?
• Bed-side testing
• No sample preparation
• Ready-to-use
• Easy to use
• Rapid read out
• Short Turn-around-Time (TAT)
Point-of-care-testing: Test Principles
POC-System
VerifyNow®
Multiplate® WBA
Test principle
Aggregometry
PFA-100®
IMPACT® -CPA
Placor PRT-7000®
Shear dependent platelet function
within whole blood
Thrombelastography (TEG®)
Global haemostasis tests, monitoring
Thrombelastometry (ROTEM®) of rate and quality of clot formation
Haemostasis Analysis System®
Ichor-Plateletworks®
Platelet counting pre- and
postactivation
HemoStatus®
Platelet procoagulant activity
VerifyNow®
• Whole blood (citrated) without further sample preparation
• No need for time-consuming centrifugation steps
• Turbidimetric based optical detection of platelet aggregation
stimulated by a specific agonist
• Disposable cartridges contain fibrinogen-coated beads and
platelet activator (3 cartridges available: aspirin, P2Y12,
GPIIb/IIIa)
VerifyNow® Technology
Results Screen VerifyNow P2Y12 Assay
Print
PRU result is ‘P2Y12-mediated
platelet aggregation’ via
adenosine diphosphate (ADP)
pathway
Base result is ‘Maximal platelet
aggregation’ via Thrombin Receptor
Activating Peptide (TRAP) pathway
which is independent of aspirin and
clopidogrel
VerifyNow® P2Y12 results can then be
reported as % platelet inhibition
VerifyNow P2Y12 PRU
Correlation of VerifyNow® with LTA
500
400
300
200
r2= 0.434
p< 0.0001
n=562
100
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60
80
RPA ADP 5 µM, %
100
Multiplate® system
(“multiple platelet function analyzer”)
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Whole blood (hirudinized)
Multiple electrodes in the disposable test cell (4 electrodes form 2 independent
sensor units), multiple channels of the instrument (5).
Detects the effects of the platelet inhibitors Aspirin®, clopidogrel and GpIIb/IIIa
antagonists, and also the newer direct ADP receptor antagonists.
No luminescence available, low shear system, does not simulate normal
haemostasis.
Continuously records platelet aggregation.
Increase of impedance by the attachment of Platelets onto the Multiplate®
sensors is transformed to arbitrary aggregation units (AU) and plotted against
time.
Three parameters:
– Area under the aggregation curve (AUC).
– Aggregation is the height of the curve. V
– Velocity is the maximum slope of the curve.
Platelet Function Assay 100 (PFA-100)
• Analyzer device and disposable
cartridge
- 40mbar
160µm
• Whole blood
• Measurment of time to occlusion
of aperture in mebrane coated
with collagen/ADP or
collagen/epinephrin under high
shear stress conditions
• Cannot distinguish
thienopyridene effect
Flow
direction
Thromboelastography (TEG)
Haemoscope's TEG® 5000 system
• Small sample of blood (typically 0.36 ml), is placed into a gently rotating
cuvette (imitates venous flow and activate coagulation) => Sensor shaft
inserted into the sample => a clot forms between the cup and the sensor.
• Speed and strength of clot formation is measured.
• Patterns of changes in strength and elasticity in the clot provide
information.
• Four values that represent clot formation are determined by this test:
– the R value (or reaction time): represents the speed of clot formation
– the K value: end or R until the clot reaches 20mm
– the angle and
– the MA (maximum amplitude). clot strength
• Coagulation Index (CI) (or overall
assessment of coagulability).
Assessing Platelet Reactivity with
Point-of care Systems
Platelet-function tests: Advantages of POC-Systems
Platelet-function tests: What kind of POC-tests are available?
Differences in test results
Differences in test results:
Are they measuring the same?
• Low shear systems (e.g. Multiplate) does not simulate
normal haemostasis
• Different stimulation reagents and dosages
• Is „baseline aggregation“ really „baseline“?
• „Units“:
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% platelet inhibition or P2Y12 reaction units (VerifyNow)
Arbitrary aggregation units (Multiplate)
Closure time (PFA-100)
Maximum aggregation, residual aggregation, … (LTA)
Platelet reacitivity index (VASP-P)
• Cut-off values
Assessing Platelet Reactivity with
Point-of care Systems
Platelet-function tests: Advantages of POC-Systems
Platelet-function tests: What kind of POC-tests are available?
Differences in test results
Cut-off values
VerifyNow: Cut off levels for „low response“
• Trenk, 2008; TRIGGER (enrolling)
> 208 PRU
• Godino, 2009
> 213 PRU
• Price et al., 2008
≥ 235 PRU
• ARMYDA-PRO, GRAVITAS (enrolling)
≥ 240 PRU
• Paniccia et al., 2007
≥ 264 PRU
Assessment of On-Clopidogrel Platelet
Reactivity by LTA and VerifyNow
LTA
17.6 ± 16.2 %
n=307
VerifyNow
161.6 ± 90.5
n=307
VerifyNow® PRU
Assessment of On-Clopidogrel Platelet Reactivity
Correlation Between LTA and VerifyNow
n=307
r2=0.441
Assessment of On-Clopidogrel Platelet Reactivity
LTA versus VerifyNow by ROC Analysis
AUC: 0.833
Sensitivity for PRU 208: 0.53
Specificity for PRU 208: 0.88
Cut off levels for „low response“
• LTA:
> 62% (Angiolillo, max. aggregation, ROC)
• TEG:
> 50% (5mM ADP)
>70% (10mM, ADP)
• VASP platelet reactivity index: >48%
• …..