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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cangrelor administered as an intravenous bolus plus a continuous infusion in healthy volunteers. Twenty-two healthy volunteers are randomized to receive 1 of 2 intravenous cangrelor dosing regimens: a 15-microg/kg bolus followed by a 2-microg/kg/min infusion or a 30-microg/kg bolus followed by a 4-microg/kg/min infusion. The infusion is continued for 60 minutes, and serial blood samples are obtained for evaluation of pharmacokinetic and pharmacodynamic parameters. Administration of an intravenous bolus followed by a continuous infusion rapidly achieves maximum concentrations of cangrelor that are associated with extensive platelet inhibition within 2 minutes. Moreover, extensive platelet inhibition is maintained throughout the infusion period with near-full recovery of platelet function within 60 to 90 minutes of terminating the infusion. The effect of high-dose cangrelor is more consistent and demonstrates a greater level of inhibition on adenosine diphosphate-induced P-selectin expression; how ever, no significant differences are observed between the 2 dosing regimens with regard to platelet aggregation or time to recovery of platelet function. Cangrelor administered as an intravenous bolus followed by a continuous infusion in healthy volunteers offers rapid and reversible inhibition of platelet function.

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It was concluded that PEG-coated and nonpegylated E78 NPs have potential blood compatibility at clinically relevant doses. Based on the calculated nanoparticle-to-platelet ratio, the concentration at which E78 NPs could potentially affect platelet function in vivo was approximately 1 mg/mL.

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ObjectiveTo evaluate the relationship between aspirin ingestion and postoperative bleeding complications, and to test the hypothesis that there is a subset of patients who are aspirin hyperresponders with a proclivity toward platelet dysfunction. Summary Background DataDespite numerous retrospective and prospective analyses, it is still controversial as to whether aspirin ingestion before coronary artery bypass grafting (CABG) is associated with significant postoperative bleeding. MethodsBetween January 1995 and December 1999, the records of 2,606 consecutive patients undergoing CABG were reviewed to identify patients with a history of aspirin ingestion up until the time of surgery. Aspirin ingestion was correlated with postoperative blood transfusion using multivariate analysis. In a subset of preoperative aspirin users (n ϭ 40), bleeding times were measured before and after aspirin use. Flow cytometry was performed in another cohort of patients with known heart disease (n ϭ 30) to determine the effect of aspirin on platelet surface receptors. ResultsDuring the 5-year study period, 63% of the CABG patients were identified as aspirin users. Among these, 23.1% required blood transfusions compared with 19% for the nonusers. Non-red blood cell transfusions were more common in aspirin users, as was reexploration for bleeding. Stratification of these results according to the frequency of aspirin use showed that aspirin is an independent multivariate predictor of postoperative blood transfusion only in high-risk patients. In the prospective studies, aspirin treatment resulted in a significant increase in the template bleeding time, an increase in platelet PAR-1 thrombin receptor activity, and a decrease in the binding of platelets to monocytes. ConclusionsThe findings support the hypothesis that aspirin is associated with a greater likelihood of postoperative bleeding. A platelet function testing algorithm that combines preoperative risk factor assessment, template bleeding times, and flow cytometry may allow the identification of aspirin hyperresponders who are at increased risk for bleeding.

The high-risk patient for readmission is a woman with diabetes, chronic lung disease, renal insufficiency, and preoperative atrial fibrillation who lives at a distance from the hospital. Readmission does not depend on periprocedural variables (eg, cardiopulmonary bypass time) or on postoperative complications. High procedural costs from the initial hospitalization do not predispose to readmission. These results suggest interventions that may reduce readmission.