Antiplatelet activity measurement at bedside

For P2Y12 inhibitors such as Clopidogrel & Ticagrelor (Platelet aggregation inhibitors).
More information at this website: http://www.accumetrics.com/en/products/verifynow-p2y12
VerifyNow Brochure: http://www.accumetrics.com/dmdocuments/system/VN-SystemOverview.pdf
VerifyNow Pocket Guide: http://www.accumetrics.com/dmdocuments/VN-PocketGuide-Interventional_OUS.pdf

PICOLO Trial: Dosing of Clopidogrel in Infants and Young Children

Li, J. et al. Circulation 2008;117:553-9.

Conlcusion: Clopidogrel 0.2 mg/kg/day in children 0-24 months of age achieves a platelet inhibition similar to that of adults with 75 mg/day.

Method:
Prospective, multicenter, randomized, placebo-controlled trial.
n=73 (50% neonates, 50% rest)
Randomized to Clopidogrel vs. Placebo in 3:1 in sequential groups.
Doses used were: 0.01 mg/kg, 0.1 mg/kg, 0.2 mg/kg, and 0.15 mg/kg. Given for 7-28 days.
Platelet aggregation was assessed by Light-Transmission Aggregometry (Maximal extent of platelet aggregation and rate of aggregation were calculated). 30-50% inhibition of 5-microMol/L ADP-induced platelet aggregation is taken as therapeutic range (similar to adults on 75 mg/day).

0.20 mg/kg daily achieved a mean of 49.3% inhibition of maximum extent of aggregation & 43.9% inhibition of rate of aggregation. Marked interpatient variability in inhibition achieved was noted within each group.

Aspirin resistance

Ref: Khaled Mansour et al. Advances in Hematology Vol 2009; Article ID 937352. 10 pages.

Tests for Platelet function &/or Aspirin resistance:

1) LTA (Light Transmission Aggregometry)

2) Point of care testing: PFA-100 device (Dade Behring, Germany)

3) Point of care testing: VerifyNow-Aspirin (Accumetrics, USA)
Aspirin reaction units > 550 is taken as evidence of Aspirin resistance.

4) Serum Thromboxane B2

5) Urinary 11-dehydro Thromboxane B2

Anti-platelet agents...to be expanded further.

Antiplatelet drugs alter the platelet activation at the site of vascular damage crucial to the development of arterial thrombosis.

Aspirin
irreversibly inhibits the enzyme COX, resulting in reduced platelet production of TXA2 (thromboxane - powerful vasoconstrictor which lowers cyclic AMP and initiates the platelet release reaction).

Dipyridamole
inhibits platelet phosphodiesterase, causing an increase in cyclic AMP with potentiation of the action of PGI2 – opposes actions of TXA2

Clopidogrel
affects the ADP-dependent activation of IIb/IIIa complex

Glycoprotein IIb/IIIa receptor antagonists block a receptor on the platelet for fibrinogen and von Willebrand factor. 3 classes:
Murine-human chimeric antibodies (e.g. abciximab)
Synthetic peptides (e.g. eptifibatide)
Synthetic non-peptides (e.g. tirofiban)

ICU: Antiplatelet agents

Cangrelor - ADP P2Y12 receptor inhibitor, 6-min half life. Immediately reversible inhibition of platelet aggregation. Continuous IV Infusion. CHAMPION trials.

Ref: NEJM Dec 2009;361(24):2382-4

Clopidogrel - ATP analogue/inhibitor, irreversible inhibition of platelet aggregation. Onset of action 1 hour. Oral administration.

Eptifibatide (Integrillin) - Gp IIb-IIIa inhibitor

Abciximab (ReoPro) - Fab fraction agains Gp IIb-IIIa receptors. Platelet inhibition lasts for 96-120 hrs (theoretically reversible)