Platelets
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Platelet activation/aggregation in sickle cell disease (SCD) may promote tissue ischemia, suggesting that antiplatelet therapy may be useful. However, the assessment of platelet function and the effect of antiplatelet therapy in blood from SCD patients may be confounded by hemolysis with the release of adenosine 5'-diphosphate (ADP). Here we evaluate the levels of platelet activation markers in SCD adolescents vs. normal controls and compare, by multiple methods, the effect of in vitro blockade of the platelet ADP receptor P2Y₁₂ by prasugrel's active metabolite, R-138727. ⋯ R-138727, in a concentration-dependent manner, inhibited platelet function in both SCD patients and healthy subjects as judged by ADP-stimulated light transmission aggregation, VerifyNow P2Y₁₂ assay, multiple electrode aggregometry, and flow cytometric analysis of platelet vasodilator-stimulated phosphoprotein, activated GPIIb-IIIa and P-selectin. The R-138727 IC₅₀s for each assay were not significantly different in SCD vs. healthy subjects. In summary: (1) The high circulating levels of platelet-monocyte and platelet-neutrophil aggregates demonstrate in vivo platelet activation in SCD and may be useful as markers of the in vivo pharmacodynamic efficacy of antiplatelet therapy in SCD. (2) The similar in vitro R-138727 IC50s in SCD and healthy subjects suggest that the prasugrel dose-dependence for platelet inhibition in SCD patients will be similar to that previously observed in healthy subjects.
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Abstract In this study, we aimed to evaluate the mean platelet voulme (MPV) levels of trauma patients who were admitted to our emergency department. Of the total 232 trauma patients, 40 females and 192 males over the age of 18 years were included in this study. Of them, 102 patients were mild trauma [Glasgow Coma Scale (GCS) 15-13)], 40 patients were moderate (GCS 12-9) and 90 patients were severe trauma (GCS 8-3) patients. ⋯ KMPV and kPlt were not correlated (p<0.05, r=0.124). Initial RTS and seventh day RTS values were significantly different (p<0.05). MPV may be helpful for emergency physicians for predicting the severity of trauma.
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Abstract Platelets play an important role in abdominal sepsis and P2Y12 receptor antagonists have been reported to exert anti-inflammatory effects. Herein, we assessed the impact of platelet inhibition with the P2Y12 receptor antagonist ticagrelor on pulmonary neutrophil recruitment and tissue damage in a model of abdominal sepsis. Wild-type C57BL/6 mice were subjected to cecal ligation and puncture (CLP). ⋯ Notably, ticagrelor completely inhibited formation of platelet-neutrophil aggregates and markedly reduced thrombocytopenia in CLP animals. In addition, ticagrelor reduced platelet shedding of CD40L in septic mice. Our data indicate that ticagrelor can reduce CLP-induced pulmonary neutrophil recruitment and lung damage suggesting a potential role for platelet antagonists, such as ticagrelor, in the management of patients with abdominal sepsis.