4 Steps in the
formation of a platelet plug
-
Adhesion
-
Activation
-
Aggregation
-
Platelet Plug
Formation
Role of
anti-platelet medications is to prevent the formation of
platelet plug by preventing adhesion, activation or aggregation
of platelets.
Primary cause
of platelet dysfunction is anti-platelet medications.
Primary role
of platelet function tests is to measure/monitor anti-platelet
medication therapy.
Anti-platelet medications Mode of Action
Aspirin:
prevents the production of Thromboxane A2.
Thromboxane A2 activates the TXA2
receptors on platelets allowing them to aggregate.
Plavix:
prevents platelets from binding to one another by
blocking the ADP receptor site, P2Y12.
GPllb/llla
Inhibitors: prevent
platelets from aggregating by blocking the final site of
platelet aggregation, the GPllb/llla receptor.
Bleeding
Time: Cannot
be used to reliably identify patients who have recently ingested
aspirin.
Light
Transmittance Aggregometry:
(gold
standard) A platelet agonist is added to platelet-rich plasma (PRP)
to initiate platelet aggregation. The change in turbidity of
the PRP is a measure of the platelet function.
Particle
Counters:
Platelet function in whole blood can be
comprehensively evaluated by flow cytometry
Urine
Thromboxane metabolite:
Thromboxane B2
is a stable and abundant metabolite of Thromboxane A2
that has platelet aggregation properties. Aspirin inhibits the
production of Thromboxane A2. A decrease in urinary
thromboxane indicates increased platelet inhibition activity.
Shear based
Assay:
Measures the
amount of time it takes blood drawn through a fine capillary to
block a membrane coated with collagen and epinephrine (CEPI) or
collagen and ADP (CADP).
(Dade Behring
PFA 100 uses this technology)
Aggregation
based Assay:
Measures the
mechanical property of a developing clot by determining the time
until initial fibrin formation.
(Thromboelastograph
TEG Platelet Mapping)
The VerifyNow
system consists of the platelet function assays,
VerifyNow
Aspirin Assay:
measures platelet
dysfunction due to aspirin. Aspirin affects platelet function
by irreversibly inhibiting an enzyme involved in the production
of Thromboxane A2 that ultimately activates the GPllb/llla
receptors involved in platelet aggregation.
The assay is
based on the ability of activated platelets to bind fibrinogen.
Fibrinogen-coated microparticles aggregate in whole blood in
proportion to the number of unblocked platelet
GP llb/llla
receptors. Light transmittance increases as activated platelets
bind and aggregate fibrinogen-coated beads. The instrument
measures this change in optical signal and reports results in
Aspirin Reaction Units (ARU)>
This is a CLIA
waived assay test.
VerifyNow
P2Y12 Assay:
measures platelet P2Y12 receptor blockade by Plavix. The assay
is based on the ability of activated platelets to bind
fibrinogen. Fibrinogen-coated microparticles aggregate in whole
blood in proportion to the number of unblocked platelet GPllb/llla
receptors. ADP/PGE1 is incorporated into the assay
channel to induce platelet activation without fibrin formation.
Light transmittance increases as activated platelets bind and
aggregate fibrinogen-coated beads. The instrument measures this
change in optical signal and reports results in P2Y12 Reaction
Units (PRU).
In a like
manner, a second activator, iso-TRAP (Thrombin Receptor
Activating Peptide) and fibrinogen-coated microparticles are
incorporated into a second channel for assay. The instrument
measures the change in transmittance in this channel calculates
the baseline platelet function for the sample, and reports the
percent inhibition result for the sample.
VerifyNow
llb/lllb Assay:
an automated,
turbidimetric, whole- blood assay designed to assess platelet
function based upon the ability of activated platelets to bind
to fibrinogen coated beads.
The detection
well of the VerifyNow™ IIb/IIIa assay device contains all of the
necessary reagents to perform this analysis. Within the well is
an activator that induces the platelet to change the
conformation of the GP IIb/IIIa receptor to a form that binds
fibrinogen. Additionally, the detection well also contains
fibrinogen-coated microbeads that bind to activated GP IIb/IIIa
receptors. The GP IIb/IIIa receptors on activated platelets will
bind to the fibrinogen-coated microbeads and cross-link to other
microbeads resulting in a clearing of the beads and platelets
within the detection well. The instrument uses light
transmittance to measure the rate at which this clearing occurs
and reports results in Platelet Aggregation Units (PAU)
Use of VerifyNow in Bleeding Mgmt.
- Alternative
to Bleeding Time
-
Preoperative Screen
- Promote
cost-effective use of blood products
- Management
of Anti-Platelet Therapy with Aspirin, Plavix and GPllb/llla
inhibitors
Every test
cartridge for each assay has built in wet quality control |
