Accumetrics VerifyNow

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Accumetrics VerifyNow
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Outline

• Review of platelets and thrombosis
• How does Aspirin/Plavix work
• How does the test work
• What is Aspirin/Plavix resistance
• How will the test be used clinically
• Limitations

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What are we trying to do?
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Formation of platelet plug
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What do activated platelets look like?
EM of dormant platelets
Activated platelets
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How do you activate platelets?
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Basic principle of test

• Incubate the following
• Human fibrinogen-coated beads
• Platelet agonist
• Buffer and Preservative
• Anticoagulated (3.2 Citrate) Blood sample from
  patient
• Measure
• Light transmittance (activated platelets will
  aggregate beads leading to increased light)

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VerifyNow Aspirin Test

• Agonist is Arachidonic Acid
• Report results as
• gt 550 ARU (Aspirin Reaction Units) No platelet
  disfunction
• lt 550 ARU Platelet disfunction consistent with
  aspirin
• Results should be interpreted with other
  laboratory and clinical data available to the
  clinician.

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Expected Values
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Test limitations

• The beads can degrade after prolonged exposure to
  room air
• Patients with inherited (i.e. VWD) or acquired
  platelet disorders have not been studied
• Patients receiving other antiplatelet agents may
  not be tested (GPIIb/IIIa inhibitors, Plavix,
  Motrin)

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P2Y12 Assay

• Instead of Arachidonic Acid, use ADP
• As a control for baseline platelet function, have
  a separated channel with iso-TRAP (Thrombin
  Receptor Activating Peptide) and
  fibrinogen-coated beads.
• Report P2Y12 Reaction Units (PRU)
• Inhibition (Base PRU) x 100
• Base
• Results in no interference with Aspirin, other
  NSAIDS.

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Expected values
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GPIIb/IIIa Assay

• Use iso-TRAP as activator (Thrombin Receptor
  Activating Peptide)
• Reports as Platelet Aggregation Units (PAU)
• No interference from aspirin, Plavix, heparin,
  warfarin, NSAIDs

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1/5 Americans uses Aspirin
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Why is Aspirin recommended?
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Coronary Events after Stenting
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New evidence suggests that for many Americans
taking aspirin, the pills do little if any good.
Recent studies have found that anywhere from
5-40 of aspirin users are nonresponsive or
resistant to the medicine. That means that
aspirin does not inhibit their blood from
clotting, as it is supposed to do.
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Variability in Aspirin response
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So what?
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136 patients for elective PCI, using VerifyNow
Assay
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In summary

• ?Aspirin/Plavix responders seem to do better with
  therapy than nonresponders?

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Mechanisms for Resistance

• Non-compliance or failure to prescribe
• Low absorption (Plavix)
• Variation in liver enzymes (P450-3A4) that
  metabolize drugs (Plavix)
• Interaction with other drug (Aspirin and Motrin,
  statins and Plavix)
• Genetic polymorphisms (COX-1, P2Y12,vWF)
• Platelet hyper-reactivity
• Increased norepinephrine

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Possible Uses

• Educate patient on importance of compliance
• Eliminate interfering medication (ibuprofen)
• Increase dose
• Switch medication
• Help decide whether someone on Asprin/Plavix is
  safe to go to the OR (assess risk of bleeding)

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Remaining Problems

• Various definitions different criteria/methods
  -gt wide range (5-40)
• How stable is this phenomenon over time?
• Are there specific populations at risk (women,
  diabetics)?
• What is the best test (Optical platelet agg,
  VerifyNow, PFA-100, Bleeding time, urinary
  thromboxane)???
• What is the clinical approach to Aspirin/Plavix
  resistance?
• Will this lead to more lives saved?