Platelets
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Randomized Controlled Trial Multicenter Study
The effects of laropiprant, a selective prostaglandin D₂ receptor 1 antagonist, on the antiplatelet activity of clopidogrel or aspirin.
Laropiprant (LRPT) is being developed in combination with Merck's extended-release niacin (ERN) formulation for the treatment of dyslipidemia. LRPT, an antagonist of the prostaglandin PGD₂ receptor DP1, reduces flushing symptoms associated with ERN. LRPT also has affinity for the thromboxane A₂ receptor TP (approximately 190-fold less potent at TP compared with DP1). ⋯ At 4 hours after the last dose, co-administration of LRPT 40 mg resulted in 3% and 41% increase in bleeding time vs. bleeding time after treatment with aspirin or clopidogrel alone, respectively. Co-administration of LPRT with clopidogrel or aspirin was generally well tolerated in healthy subjects. Co-administration of multiple doses of LRPT 40 mg and clopidogrel 75 mg or aspirin 81 mg had no clinically important effects on bleeding time or platelet aggregation.
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Platelet size, measured as mean platelet volume (MPV), is associated with platelet reactivity. MPV has been identified as an independent risk factor for future stroke and myocardial infarction. The aim of this study was to determine the association of MPV with the development of stoke in patients with atrial fibrillation (AF). ⋯ Furthermore, AF patients with an MPV over 8.85 fL had high stroke risk without anticoagulation, especially in the low thromboembolic risk group (Log-Rank <0.0001). The results of this study show that MPV was a predictive marker for stroke; its predictive power for stroke was independent of age, gender, and other CHADS(2) score components in patients with AF. These findings suggest that anticoagulation may be needed in patients with a high MPV, even if they have low to intermediate traditional thromboembolic risk (CHADS(2) score <2).
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Morning increase in the occurrence of myocardial infarction, stroke and sudden cardiac death is a well-recognized phenomenon, which is in line with a morning enhancement of platelet aggregation. We investigated whether platelet inhibition during clopidogrel and aspirin therapy varies during the day. Fifty-nine consecutive patients (45 men and 14 women) with first ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary interventions (pPCI) on dual antiplatelet therapy were prospectively enrolled into the study. ⋯ In contrast, no diurnal variation in the antiplatelet effect of aspirin was observed. In conclusion, in patients presenting with STEMI undergoing pPCI, platelet inhibition by clopidogrel is less strong in the midmorning hours. This periodicity in platelet aggregation in patients on dual antiplatelet therapy should be taken into consideration when assessing platelet function in clinical studies.
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Several antiplatelet drugs that are used or in development as antithrombotic agents, such as antagonists of P2Y₁₂ and EP3 receptors, act as antagonists at G(i)-coupled receptors, thus preventing a reduction in intracellular cyclic adenosine monophosphate (cAMP) in platelets. Other antiplatelet agents, including vascular prostaglandins, inhibit platelet function by raising intracellular cAMP. Agents that act as antagonists at G(i)-coupled receptors might be expected to promote the inhibitory effects of agents that raise cAMP. ⋯ Cangrelor and DG-041 were able to increase the ability of agents to raise cAMP in platelets as measured by increases in VASP-P. Thus, P2Y₁₂ antagonists and the EP3 antagonist DG-041 are able to promote inhibition of platelet aggregation brought about by natural and other agents that raise intracellular cAMP. This action is likely to contribute to the overall clinical effects of such antagonists after administration to man.
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Chronic obstructive pulmonary disease (COPD), an increasing global health problem, may be complicated by acute atherothrombotic events. Although systemic inflammation plays the leading role in atherothrombotic processes, platelet activation and increased coagulation together with oxidative stress can significantly exacerbate atherosclerosis in COPD patients. ⋯ Cigarette smoking had no influence on these results. The presence of systemic inflammation was clearly proved by the increase in classical inflammatory markers (CRP, WBC and segmented neutrophil count).