function testing is not embedded into schedule clinical practice because zero

function testing is not embedded into schedule clinical practice because zero optimal easy reproducible and multipathway platelet aggregation check could be accomplished in vitro. platelet receptor occupancy was in conjunction with better electrocardiographic and angiographic result.3 Finally in STEMI individuals undergoing major percutaneous intervention (PCI) higher degrees of platelet aggregation inhibition by abciximab were recently found to be associated with better myocardial reperfusion.5 Therefore measuring platelet function in patients with an acute coronary artery syndrome is gaining interest to select patients at high risk of an unfavourable thrombotic event. In the study by Van Werkum et al. in this edition of the Journal platelet function is usually measured in patients with an acute coronary syndrome randomised to abciximab high-dose tirofiban or placebo. Only 40 to 50% of platelets were inhibited in the abciximabtreated patients whereas platelet inhibition reached 80% in the patients treated with high-dose tirofiban.6 The authors refer to studies using TARGET trial dosing in which low-dose tirofiban achieved only 60 to 66% platelet inhibition and resulted in more procedure-related ischaemic events than abciximab which produced 90 to 95% platelet inhibition (using optical light aggregometry).7 8 Therefore Van Werkum et al. used the high-dose tirofiban instead for comparison with abciximab and placebo. Nevertheless even in the high-dose tirofiban there was still considerable platelet aggregation in vitro (20% of platelets). In early dose-finding studies a level of platelet aggregation inhibition of >80% was strived for.9 10 The study results of Van Werkum et al. show striking similarities with a previous study which used the same platelet function test.11 Again only Iguratimod 46% platelet aggregation inhibition was found in the abciximab group and 86% platelet aggregation inhibition in Iguratimod the high-dose tirofiban group. The explanation for this ‘drug resistance’ might be related to the dose of the drug or the underlying disease. This lack of optimal platelet inhibition could be described as glycoprotein IIB/IIIA ‘resistance’. However does resistance against an antiplatelet therapy exist? Platelet function assessments and resistance In the past years the terms aspirin resistance and clopidogrel resistance have emerged to describe different phenomena: 1) inability to prevent thrombotic complications 2 a platelet aggregation inhibition measured by in vitro platelet function assessments below certain cut-off values 3 insufficient inhibition of plasma or urinary biochemical markers for platelet aggregation. ‘Resistance’ as a description of interindividual variability in the outcome of a platelet function test is usually incorrect because the definition of resistance is dependent on a cut-off value. The cut-off values for aspirin or clopidogrel Iguratimod resistance are highly variable in the literature. Above all most of the cutoff values are defined by measuring healthy volunteers. The response of sufferers with unpredictable coronary artery disease or myocardial infarction is certainly however not the same as the outcome of the platelet function check in healthful volunteers.12 In the environment of the acute coronary symptoms hyperaggregable platelets circulate which require more extensive antiplatelet therapy. For instance in one of the most recent articles by Gurbel et al. the cut-off value for Rabbit Polyclonal to CXCR7. the bleeding time measured by PFA-100 collagen cartridge was 193 seconds.13 This value however is derived from the manufacturers and is based on a normal value in healthy volunteers. Since these values can hardly be extrapolated to patients with coronary artery disease defining aspirin or clopidogrel resistance based on Iguratimod cut-off values derived from healthy volunteers is usually inadequate. Another argument against describing the interindividual platelet aggregation response to an antiplatelet drug as ‘resistant’ is the normal pharmacodynamic and pharmacokinetic variability.14 It seems more likely that this interindividual response to aspirin and clopidogrel is a normally divided bell-shaped reaction depending on both pharmacodynamic and pharmacokinetic variability and the underlying disease and type of platelet function test used rather than a separate group of patients unable to respond to the drug.15 Therefore also.