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

Abstract

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.

“Super” SERPINs—A stabilizing force against fibrinolysis in thromboinflammatory conditions

“…Misalignment between the internal and external clock, for instance during daylight saving time, have been associated with increased risk of MI ( 113 ). A recent study on acute MI determined a correlation between tPA and PAI-1 levels with highest levels recorded in the morning ( 114 ), in agreement with earlier studies ( 66 – 68 , 70 ). However, treatment with the anti-platelet drug clopidogrel gave rise to elevated levels of PAI-1 in those acute MI patients resistant to clopidogrel, but not clopidogrel-sensitive patients ( 114 ).…”

“…A recent study on acute MI determined a correlation between tPA and PAI-1 levels with highest levels recorded in the morning ( 114 ), in agreement with earlier studies ( 66 – 68 , 70 ). However, treatment with the anti-platelet drug clopidogrel gave rise to elevated levels of PAI-1 in those acute MI patients resistant to clopidogrel, but not clopidogrel-sensitive patients ( 114 ). These interesting data suggest that increased evening PAI-1 may relate to platelet activation and underscore the diurnal changes that occur both naturally in this SERPIN and in response to drugs.…”