title: Evaluation of the INNOVANCE PFA P2Y test cartridge: sensitivity to P2Y(12) blockade and influence of anticoagulant.
abstract: Monitoring of platelet ADP receptor P2Y(12) inhibition may be performed by a variety of platelet function assays. Given the lack of sensitivity of the existing PFA-100® cartridge formulations to detect P2Y(12) inhibition, a new cartridge for the PFA-100 (INNOVANCE® PFA P2Y) has recently been developed. The performance of the new PFA-100 test cartridge was compared with standard collagen/ADP (CADP) and collagen/epinephrine (CEPI) cartridges, light transmission aggregometry, vasodilator-stimulated phosphoprotein, the VerifyNow® P2Y(12) assay and multiple electrode aggregometry. In this study, 20 normal blood samples anticoagulated with either citrate or hirudin were spiked with two different clinically relevant concentrations (1 and 10 µM final concentration) of the prasugrel active metabolite (R-138727, Lilly/Daiichi Sankyo) for 30 min at 37°C. Comparison of the platelet function tests demonstrated that all tests (except CADP and CEPI) were substantially inhibited by 10 µM R-138727. Intermediate results were typically obtained with 1 µM R-138727 in citrated blood. However, both MEA ADP and ADPHS tests were highly sensitive to 1 µM R-138727 in hirudin anticoagulated blood. Further comparison of citrate or hirudin blood samples (N = 5) revealed that all platelet tests (except CEPI) became more sensitive to 1 µM R-138727 in hirudinized blood. The INNOVANCE PFA P2Y cartridge proved to be sensitive to P2Y(12) inhibition and was comparable to other currently available platelet function tests. The sensitivity of all platelet function tests for detecting in vitro inhibition of P2Y(12) is markedly different depending on the anticoagulant used.
authors.affiliation: Oxford Haemophilia and Thrombosis Centre, Churchill Hospital, Oxford OX3 7LJ, UK.
authors.forename: Abbie
authors.initials: A
authors.lastname: Edwards
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Jakubowski
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Rechner
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Sugidachi
authors.forename: Paul
authors.initials: P
authors.lastname: Harrison
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D019719:Diagnostic Equipment; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology*; D011933:Reagent Kits, Diagnostic; D058925:Receptors, Purinergic P2Y12 / Q000097:blood; D013876:Thiophenes / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D010879:Piperazines; D058921:Purinergic P2Y Receptor Antagonists; D011933:Reagent Kits, Diagnostic; D058925:Receptors, Purinergic P2Y12; D013876:Thiophenes; D000068799:Prasugrel Hydrochloride