Assessment of platelet functional activity in healthy individuals and patients receiving antiplatelet therapy. Possible inconsistencies between aggregation and flow cytometry tests.

Platelet functional activity was assessed in healthy volunteers (HV, n=92), patients with stable angina pectoris (SA, n=42) and acute coronary syndrome (ACS, n=73), treated with acetylsalicylic acid (ASA) + clopidogrel and ASA + ticagrelor, respectively. In all HV and patients we have compared parameters of platelet aggregation (maximum light transmission and velocity, Tmax and Vmax) and parameters, characterizing exposure of platelet activation markers, evaluated by flow cytometry. HV platelets were activated by 10 µM, 1 µM TRAP, and 20 µM, 5 µM, 2.5 µM ADP; patient platelets were activated by 10 µM TRAP and by 20 µM and 5 µM ADP. Strong and significant correlations between the aggregation and flow cytometry parameters (the r correlation coefficient from 0.4 up to >0.6) most frequently were registered in HV platelet during activation by 1 µM TRAP and in SA patients during platelet activation by 20 µM and 5 µM ADP. However, in many other cases these correlations were rather weak (r < 0.3) and sometimes statistically insignificant. In HV the differences in PAC-1 binding parameters between platelets activated by 10 µM TRAP (the strongest agonist) and all ADP concentrations were negligible (≤ 10%), while CD62P binding (at all ADP concentrations) and LTA parameters for (5 µM and 2.5 µM ADP) were significantly lower (by 40-60%). Antiplatelet therapy in patients decreased all parameters as compared to HV, but to varying extents. For 10 µM TRAP the MFI index for PAC-1 binding (40-50% decrease) and for both ADP concentrations the Tmax values (60-85% decrease) appeared to be the most sensitive in comparison with the other parameters that decreased to a lesser extent. The data obtained indicate a possibility of inconsistency between different LTA and flow cytometry parameters in assessing platelet activity and efficacy of antiplatelet drugs.

Assessment of platelet function after discontinuation of ticagrelor.

BACKGROUND: Patients presenting with acute coronary syndromes (ACS) are often treated by percutaneous coronary intervention (PCI) with insertion of coronary artery stents and a majority receive dual antiplatelet therapy (DAPT), usually a combination of a COX-1 inhibitor (aspirin) and a P2Y12 inhibitor (eg ticagrelor). Not seldom the question arises as to when DAPT should be discontinued prior to interventional surgery. This study was done with the primary aim of investigating thrombocyte function immediately prior to and after discontinuation of ticagrelor. MATERIALS AND METHODS: In this prospective, longitudinal, observational study including 24 patients, venous blood was obtained from patients on day 0, before stopping maintenance dose of 90 mg ticagrelor twice daily, and then on days 1, 3, 5, and 8, after discontinuation. Samples were analyzed using Multiplate® and VerifyNow® . RESULTS: Prior to urgent surgery platelet aggregation >30 aggregation units (Multiplate® ) and >208 P2Y12 reaction units (VerifyNow® ) have been shown to correlate with reduced risk of peri- and postoperative bleeding risk. On day 3 after ticagrelor discontinuation, 100% (P = .016) and 67% (P=<.001) of patients had reached these levels on Multiplate® and VerifyNow® , respectively. On day 5, the corresponding figures were 100% (P = .016) and 78% (P=<.001). CONCLUSION: Discontinuation of ticagrelor for 3 days resulted in return of adequate platelet function in all patients on Multiplate® and in a majority of patients on VerifyNow® , indicating a lower bleeding risk. A bedside test for platelet function may be considered if time to anticipated surgery is less than 5 days after ticagrelor discontinuation.

Is ticagrelor worth its high cost and side-effects?

Ticagrelor is a reversible P2Y12 receptor antagonist that is more potent than clopidogrel. When used in combination with aspirin, it reduces cardiovascular events in patients with acute coronary syndrome. However, unbiased review of 5 randomised controlled trials indicates that although statistically significant, the clinical superiority of ticagrelor over clopidogrel is modest. Thus, identification of patients who benefit the most from ticagrelor is a priority. Besides bleeding issues, ticagrelor can frequently cause bouts of dyspnoea, which requires ticagrelor replacement by another P2Y12 receptor antagonist, with a loading dose.