ITC VerifyNow System Platelet Reactivity Test - Manual (Page 8)

Introduction - 1
Page 4 14439.C 03/2013 VerifyNow System User Manual | USA
1.1.1 Aspirin Test
Acetylsalicylic acid (aspirin) has a significant antiplatelet effect by blocking the production of
thromboxane A2 (TXA2). A potent platelet agonist, thromboxane A2 is released by activated platelets
and acts to cause vasoconstriction and amplify platelet recruitment by binding to thromboxane receptors
on the surface of circulating platelets. In an activated platelet, arachidonic acid is converted by cyclo-
oxygenase (COX-1) to prostaglandin G
2
(PGG
2
) and PGH
2
and then to TXA2. Aspirin affects platelet
function by irreversibly inhibiting the cyclo-oxygenase (COX) activity of prostaglandin (PG) H-synthase,
which in turn blocks the metabolism of arachidonic acid to TXA2. The primary pharmacological effect
of aspirin on platelets is to decrease the activation of the GP IIb/IIIa receptor and activation of other
platelets.
VerifyNow Aspirin Test is a qualitative test to aid in the detection of platelet dysfunction due to aspirin
ingestion in whole blood for the point-of-care or laboratory setting. The test incorporates the agonist
arachidonic acid to activate platelets, and it measures platelet function based upon the ability of
activated platelets to bind to fibrinogen. Fibrinogen-coated microparticles aggregate in whole blood in
proportion to the number of activated platelet GP IIb/IIIa receptors. If aspirin has produced the expected
antiplatelet effect, such aggregation will be reduced. The VerifyNow Aspirin Test reports the extent of
platelet aggregation as aspirin reaction units (ARUs). Given an ARU range of 350-700, ARU values less
than 550 are consistent with aspirin-induced inhibition of platelet function, whereas values greater than
or equal to 550 ARUs are not consistent with aspirin-induced inhibition.
NOTE: The Aspirin Test is not for use in patients with underlying congenital platelet abnormalities, patients with non-
aspirin induced acquired platelet abnormalities or in patients receiving non-aspirin anti-platelet agents. Refer to the
VerifyNow Aspirin package insert for information to be considered for patients receiving NSAIDS. The Aspirin Test
may be used in patients treated with selective COX-2 inhibitors, e.g. celecoxib (Celebrex ® ).
1.1.2 PRUTest
P2Y12 inhibitors (e.g. thienopyridines) are a class of therapy that has significant antiplatelet effect
by inhibiting adenosine diphosphate (ADP)-mediated platelet activation. Platelet activation by ADP
plays a key role in the development of arterial thrombosis. When secreted by activated platelets from
storage granules, the ADP activates additional platelets in circulation through two G protein-coupled P2
receptors, P2Y1 and P2Y12. P2Y12 inhibitors irreversibly inhibit ADP binding to the P2Y12 receptor on
the platelet surface. By blocking this receptor, these agents interfere with additional platelet activation,
degranulation, and - by inhibiting the modification of the glycoprotein IIb/IIIa receptor— aggregation.
The VerifyNow PRUTest is a whole blood test used in the laboratory or point of care setting to measure
P2Y12 receptor blockade. The test incorporates the agonist ADP to activate platelets. The VerifyNow
PRUTest also uses PGE1 to increase intraplatelet cAMP and reduce the contribution of the P2Y1
receptor on activation. This makes the test more specific for the effects of ADP on the P2Y12 receptor. It
measures platelet function based upon the ability of activated platelets to bind to fibrinogen. Fibrinogen-
coated microparticles aggregate in whole blood in proportion to the number of activated platelet GP IIb/
IIIa receptors; and if the P2Y12 inhibitor has produced the expected antiplatelet effect, such aggregation
will be reduced. The VerifyNow PRUTest reports the extent of platelet aggregation in P2Y12 reaction
units (PRU). PRU reports the amount of ADP-mediated aggregation specific to the platelet P2Y12
receptor, and is calculated as a function of the rate and extent of platelet aggregation in the ADP
channel.
NOTE: Refer to the VerifyNow PRUTest package insert for information to be considered for
patients receiving anti-platelet agents.