title: Use of Aspirin in normalization of recombinant human erythropoietin-mediated hyper-reactivity of platelets in rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Pharmacology, Zyd us Research Centre, Sarkhej-Bavla, Moraiya, Ahmedabad, Gujarat, India ; Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors.forename: Hitesh M
authors.initials: HM
authors.lastname: Soni
authors.affiliation: Departments of Pharmacology, Zyd us Research Centre, Sarkhej-Bavla, Moraiya, Ahmedabad, Gujarat, India ; Department of Pharmacology, School of Pharmacy and Technology Management (Shirpur Campus), Narsee Monjee Institute of Management Studies University, Mumbai, Maharashtra, India.
authors.forename: Amit M
authors.initials: AM
authors.lastname: Vekaria
authors.affiliation: Departments of Pharmacology, Zyd us Research Centre, Sarkhej-Bavla, Moraiya, Ahmedabad, Gujarat, India.
authors.forename: Akshyaya C
authors.initials: AC
authors.lastname: Rath
authors.affiliation: Department of Pharmacology, School of Pharmacy and Technology Management (Shirpur Campus), Narsee Monjee Institute of Management Studies University, Mumbai, Maharashtra, India.
authors.forename: Sateesh
authors.initials: S
authors.lastname: Belemkar
authors.affiliation: Departments of Pharmacology, Zyd us Research Centre, Sarkhej-Bavla, Moraiya, Ahmedabad, Gujarat, India.
authors.forename: Mukul R
authors.initials: MR
authors.lastname: Jain
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects*; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010976:Platelet Count; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D001241:Aspirin
keywords: Aspirin; chronic kidney disease; platelet; rat; recombinant human erythropoietin