General discussion and summary
percentage of increased RP was independently related to postoperative myocardial injury and 30-day mortality in patients undergoing major noncardiac surgery, aged â&#x2030;Ľ 60 year. Increased percentage RP may reflect extensive cardiovascular disease in patients. Future prospective studies with consequent adjustment of cardiovascular risk management after RP measurement, should determine the clinical relevance. Potentially RP can complement or replace platelet reactivity testing in future tailored antiplatelet therapy. 2. Another challenge in accurate platelet reactivity testing is that, due to the heterogeneity in platelet reactivity tests, there is no clear definition of high platelet reactivity. This leads to difference in prevalence of high platelet reactivity between studies studying the same patient population. For patients with peripheral arterial disease undergoing PTA a large variance in proportion of high platelet reactivity existed between the VerifyNow, VASP- assay and flow cytometry (Chapter 4). Frequency of high platelet reactivity despite aspirin or clopidogrel treatment was also different in patients undergoing carotid endarterectomy, when measured with either flow cytometry or VerifyNow (Chapter 7). 3. To further optimize platelet reactivity testing a consensus should be made about the usage of either venous or arterial blood. Recently a study compared platelet reactivity measured with LTA, VerifyNow and PFA-100 in blood from the coronary artery-, femoral artery and femoral vein, showing wide differences between the utilized tests as well as between coronary and venous blood.3 The results of a study from the Antonius Ziekenhuis evaluating the difference in platelet reactivity, measured by VerifyNow, in venous or arterial blood can be expected soon. 4. Future research should also focus on potential variability in platelet reactivity and the consequent timing of testing; data have demonstrated that the mean platelet reactivity across a population is constant in different samples. 4 In contrast the same study shows when evaluating each patient individually, that 15.7% of patients taking clopidogrel 75 mg and 11.4% of patients taking 150 mg had a change in their responder status when tested at 2 different time points (p < 0.001). In this thesis we observed a large variance of high platelet reactivity in patients with PAD when testing <24 hours or > 24 hours after intervention in the same patient (Chapter 4). Studies on healthy subjects who are not on APT, have shown that platelet reactivity can vary significant over time. 5,6 These findings suggest that many physiological factors, other than medications, may affect platelet function even in normal individuals. For patients on clopidogrel treatment, one can only speculate which factors might contribute to intra- individual platelet reactivity; potential factors might include either true alterations in platelet reactivity due to fluctuations in platelet production and expression of the P2Y12 receptor, changes in hepatic metabolism (based on CYP2C19 mutated alleles) altering the level of clopidogrel bio activation, unrecognized noncompliance, or artefactual changes in measured platelet reactivity due to technical issues affecting the platelet reactivity tests.
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