Assessment of clopidogrel non-response by the PFA-100® system using the new test cartridge INNOVANCE® PFA P2Y

Birgit Linnemann (1) , Jan Schwonberg (1) , Andreas R. Rechner (2) , Helen Mani (1) , Edelgard Lindhoff-Last (1)

1 Division of Vascular Medicine, Department of Internal Medicine
2 Assay Development Hemostasis

Until now, the PFA-100® system has been considered unsuitable for monitoring clopidogrel efficacy. The authors evaluated platelet function in peripheral arterial occlusive disease (PAOD) patients using a new PFA-100® test cartridge (product name: INNOVANCE® PFA P2Y*) specifically designed for this purpose. Twenty-two stable PAOD patients on antithrombotic therapy with clopidogrel alone ( = 22) and 18 patients undergoing a peripheral catheter intervention, preliminarily treated with 100 mg/day of aspirin followed by co-administration of clopidogrel (loading dose 300 mg, maintenance dose 75 mg/day), were enrolled in this study. Defining non-responsiveness to clopidogrel as an aggregation response within the reference range (90% central interval), four (18.2%) non-responders using light transmittance aggregometry (LTA) induced by 5 µM adenosine diphosphate (ADP) and six (27.3%) non-responders using LTA induced by 2 µM ADP (LateAggr >72.1% and >42.9%, respectively) were identified. INNOVANCE® PFA P2Y* determined six (27.3%) non-responders (CT < 87 s). Agreement between the two aggregometry assays and INNOVANCE® PFA P2Y* on the definition of clopidogrel response and non-response exceeded 70%. Only three patients were uniformly identified as clopidogrel non-responders by all three assays. When clopidogrel was co-administered with aspirin, two (11.1%) non-responders to clopidogrel were detected with INNOVANCE® PFA P2Y*, whereas ADP-induced LTA found all patients to be responsive. INNOVANCE® PFA P2Y* appears to be suitable for monitoring the effect of clopidogrel on platelet function. Its sensitivity in detecting responsiveness or non-responsiveness to clopidogrel is comparable to ADP-induced LTA. Additional prospective studies are needed to clarify the clinical relevance of the test results and classification obtained with INNOVANCE® PFA P2Y*.

Mots clés: Clopidogrel; Antiplatelet therapy; Non-response; PFA-100® system; INNOVANCE® PFA P2Y

Birgit Linnemann, Jan Schwonberg, Andreas R. Rechner, Helen Mani, Edelgard Lindhoff-Last. Assessment of clopidogrel non-response by the PFA-100® system using the new test cartridge INNOVANCE® PFA P2Y. Annals of Hematology, 2010, 89 (6), pp.597-605. ⟨10.1007/s00277-009-0881-9⟩. ⟨hal-00497395⟩