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.

[Efficiency and safety of using the modified protocol for the administration of the domestic class III antiarrhythmic drug for the relief of paroxysmal atrial fibrillation].

AIM: Evaluation of the efficacy and safety of the modified refralon administration protocol for the relief of paroxysmal atrial fibrillation (AF). MATERIALS AND METHODS: The study included 39 patients (19 men, mean age 6312.8 years). All patients, after excluding contraindications in the intensive care unit, were injected intravenously with refralon at an initial dose of 5 mg/kg. If AF was preserved and there were no contraindications, after 15 min, repeated administration was performed at a dose of 5 mg/kg (total dose of 10 mg/kg). After another 15 min, while maintaining AF and the absence of contraindications, the third injection of the drug was performed at a dose of 10 mg/kg (total dose of 20 mg/kg). In the absence of relief and the absence of contraindications, another injection of refralon at a dose of 10 mg/kg was performed after another 15 min (in this case, the maximum total dose of 30 mg/kg was reached). After each injected bolus and before the introduction of the next one, the ECG parameters and the general condition of the patient were assessed. The patient was monitored for 24 hours to exclude the arrhythmogenic effect and other possible adverse events. RESULTS: Restoration of sinus rhythm (SR) was noted in 37 patients out of 39 (95%). Of these, 19 people (48.7%) had SR recovery after the administration of a minimum dose of refralone of 5 mg/kg. The effectiveness of the total dose of 10 mg/kg was 76.9%, the dose of 20 mg/kg was 89.7%, and the dose of 30 mg/kg was 95%. Only two patients did not recover HR after administration of the maximum dose of refralon 30 mg/kg. Pathological prolongation of the QTc interval (500 ms) was recorded in 5% of patients. Not a single case of ventricular arrhythmogenic action (induction of Torsade de pointes) has been reported. Bradyarrhythmias (pauses, bradycardia) were registered in 13% of cases, were of a transient nature. CONCLUSION: Refralon has a high efficiency of relief (95%) of paroxysmal AF, while in almost half of cases (48.7%), SR recovery is achieved using the minimum dose of refralon 5 mg/kg. Despite the prolongation of the QTc500 ms recorded in 5% of cases, none of the patients developed Torsade de pointes after administration of the drug.