Modulation of platelet activation in chronic kidney disease patients on erythropoiesis-stimulating agents.

BACKGROUND: Clinical trials demonstrate either no benefit or increased risk of cardiovascular events and mortality in patients with chronic kidney disease (CKD) targeted for higher hemoglobin levels, who are treated with erythropoiesis-stimulating agents (ESAs). The mechanism underlying this observation remains unexplained. METHODS AND RESULTS: We assessed platelet activation by measuring soluble P-selectin (sPsel), CD40 ligand (CD40L), and circulating microparticles (CMP) in patients with CKD. Higher hemoglobin levels were associated with increased Psel levels in patients on ESAs but not in ESA-naïve anemic and nonanemic patients. Psel positively correlated with CMP and CD40L in both anemic and nonanemic patients. Multivariate linear regression analysis revealed an association between increased Psel levels and hemoglobin concentration in patients receiving ESAs. CONCLUSIONS: Anemic CKD patients on ESAs demonstrate increased levels of markers of platelet activation. These observations suggest a potentially complex interplay between platelet activation, impaired kidney function, and treatment of CKD anemia with ESAs.

Pharmacokinetics of enoxaparin in patients undergoing percutaneous coronary intervention with and without glycoprotein IIb/IIIa therapy.

The pharmacokinetic profile of enoxaparin was established in a substudy involving 1054 patients undergoing percutaneous coronary intervention. Patients enrolled in the National Investigators Collaborating on Enoxaparin 1 (NICE-1) trial received enoxaparin as a 1.0-mg/kg intravenous bolus. Patients enrolled in the NICE-4 trial received enoxaparin as a 0.75-mg/kg intravenous bolus followed by abciximab as a 0.25-mg/kg bolus and a 0.125-mcg/kg/min 12-hour infusion. Blood samples were collected at six time points over 12 hours and analyzed for plasma anti-Xa, anti-IIa, and Heptest (Haemachem Inc., St. Louis, MO) activity using specific and sensitive assay methods. Data were similar in both trials. Plasma anti-Xa, anti-IIa, and Heptest activity peaked shortly after the enoxaparin bolus and declined in parallel over the ensuing 12 hours. Area under the curve and peak activity were greatest for Heptest activity and least for anti-IIa activity. Values for clearance, volume of distribution, volume of distribution at steady state, and elimination rate constant were on the order of 10 mL/h/kg, 48 mL/kg, 45 mL/kg, and 0.22/h, respectively. These measures suggest that the use of abciximab in combination with enoxaparin during percutaneous coronary intervention is unlikely to affect the pharmacokinetics of enoxaparin.