Diurnal Oscillations of Fibrinolytic Parameters in Patients with Acute Myocardial Infarction and Their Relation to Platelet Reactivity: Preliminary Insights.

There is limited information about diurnal changes in fibrinolysis parameters after acute myocardial infarction (AMI) and their relationship with on-treatment platelet reactivity. The aim of this study was to assess tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-1), α2-antiplasmin (α2-AP) activity, and plasmin-antiplasmin (PAP) complexes in 30 AMI patients taking dual antiplatelet therapy (DAPT), i.e., acetylsalicylic acid and clopidogrel. Fibrinolytic parameters were assessed at four time points (6 a.m., 10 a.m., 2 p.m., and 7 p.m.) on the third day after AMI using immunoenzymatic methods. Moreover, platelet reactivity was measured using multiple-electrode aggregometry, to assess potential differences in fibrinolytic parameters in low/high on-aspirin platelet reactivity and low/high on-clopidogrel platelet reactivity subgroups of patients. We detected significant diurnal oscillations in t-PA and PAI-1 levels in the whole study group. However, PAP complexes and α2-AP activity were similar at the analyzed time points. Our study reveals a potential impact of DAPT on the time course of fibrinolytic parameters, especially regarding clopidogrel. We suggest the presence of diurnal variations in t-PA and PAI-1 concentrations in AMI patients, with the highest levels midmorning, regardless of platelet reactivity. Significantly elevated levels of PAI-1 during the evening hours in clopidogrel-resistant patients may increase the risk of thrombosis.

Diurnal variations in tissue factor and tissue factor pathway inhibitor concentrations in relation to on-treatment platelet reactivity: an analysis of patients with acute myocardial infarction.

The aim of the study was to evaluate diurnal changes of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) concentrations in relation to on-treatment platelet reactivity. The study group included 51 patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention and dual antiplatelet therapy. TF and TFPI concentrations were assessed using enzyme-linked immunosorbent assay kits. We found a significant increase of TF concentration in clopidogrel-resistant, but not clopidogrel-sensitive, patients at 10.00 a.m. (410.66 pg/mL) in comparison with 6.00 a.m. (250.99 pg/mL), 14.00 p.m. (255.12 pg/mL) and 19.00 p.m. (267.58 pg/mL). Moreover, TF concentration at 10.00 a.m. was 30% higher in clopidogrel-resistant than clopidogrel-sensitive patients (p = .043). We failed to demonstrate diurnal variation in TFPI concentration in clopidogrel-resistant patients. However, TFPI concentration in clopidogrel-sensitive patients was significantly higher at 10.00 a.m. as compared with other sampling points (p < .05). We observed a marked elevation in TF concentration at 10.00 a.m. only in aspirin-resistant patients and a significant increase in TFPI concentration at 10 a.m. only in aspirin-sensitive patients. Our findings suggest the presence of diurnal variations in TF and TFPI concentrations in AMI patients, with the highest thrombotic risk in patients with high on-treatment platelet reactivity in the midmorning.

Increased morning ADP-dependent platelet aggregation persists despite dual antiplatelet therapy in patients with first ST-segment elevation myocardial infarction: Preliminary report.

BACKGROUND: Numerous trials have reported on the morning increase in the occurrence of myocardial infarction, stroke and sudden cardiac death. Similarly, enhanced morning platelet aggregation has been observed in healthy individuals and in subjects with coronary artery disease without adequate antiplatelet treatment. The purpose of the study was to assess circadian variation in platelet aggregation in patients with first ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary interventions (pPCI) and dual antiplatelet therapy. METHODS: Fifteen consecutive patients (12 men and 3 women) were prospectively recruited into the study. Blood samples were collected at 6.00 a.m., 10.00 a.m., 2.00 p.m. and 7.00 p.m. on the third day of hospitalization. Aggregation in response to arachidonic acid and adenosine diphosphate (ADP) was assessed in the whole blood on a new generation impedance aggregometer. RESULTS: A morning increase of 75% in ADP-dependent platelet aggregation was noted in the study population (p < 0.04). In contrast, we failed to show any significant diurnal variation in arachidonic acid-mediated platelet aggregation. The magnitude of the morning surge in platelet aggregation after ADP stimulation did not correlate with its baseline level. CONCLUSIONS: Increased morning ADP-dependent platelet aggregation persists despite dual antiplatelet therapy in patients with first STEMI undergoing pPCI. The clinical significance of this finding remains to be demonstrated.