Use of Aspirin in normalization of recombinant human erythropoietin-mediated hyper-reactivity of platelets in rats

• Published in: Indian journal of pharmacology 2014-05, Vol.46 (3), p.328-333
• Main Authors: Soni, Hitesh M, Vekaria, Amit M, Rath, Akshyaya C, Belemkar, Sateesh, Jain, Mukul R
• Format: Article
• Language: English
• Subjects: Anemia; Animals; Aspirin; Aspirin - pharmacology; Bleeding Time; Blood platelets; Blood Platelets - drug effects; Cardiovascular diseases; Drug therapy; Epoetin Alfa; Erythropoietin; Erythropoietin - pharmacology; Health aspects; Humans; Kidney diseases; Male; Pharmacology; Physiological aspects; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Platelet Count; Rats, Wistar; Recombinant Proteins - pharmacology; Risk factors; Rodents
• ISSN: 0253-7613; 1998-3751
• DOI: 10.4103/0253-7613.132187

The cytokine erythropoietin is the primary stimulator of erythropoiesis and recombinant human erythropoietin (rHuEPO), which is widely used in the treatment of anemia associated with advanced chronic kidney disease (CKD). Adverse cardiovascular outcomes have been observed during clinical trials of anemia correction with rHuEPO in CKD patients. We investigated the effects of short-term, high-dose treatment with rHuEPO on platelet reactivity and effects of aspirin on platelet reactivity in healthy rats. Animals received three daily dose of rHuEPO (25 μg/kg s.c.). Platelets were isolated after 48 h of last dose of rHuEPO to study the arachidonic acid-induced platelet aggregation. Aspirin (75 mg/kg p.o.) was given to animals just before 1 h of isolation of platelets. In rats, treatment with rHuEPO increased platelet reactivity and platelet count. The increased platelet reactivity was paralleled by decreased time-to-occlusion (TTO) in arterial thrombosis model, and decreased bleeding time after tail transection in rats. Treatment with rHuEPO followed by single dose of aspirin showed significant reduction in TTO and bleeding time as compared with aspirin-treated group. These findings suggest that rHuEPO increases platelet reactivity and aspirin normalizes the hyper-reactive platelet and may reduce the cardiovascular events associated with rHuEPO in CKD patients.