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

Hiteshkumar Soni, Amit M. Vekaria, Akshyaya C. Rath, Sateesh Belemkar, Mukul R. Jain

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objectives: 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. Materials and 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.

Original languageEnglish (US)
Pages (from-to)328-333
Number of pages6
JournalIndian Journal of Pharmacology
Volume46
Issue number3
DOIs
StatePublished - Jan 1 2014

Fingerprint

Erythropoietin
Aspirin
Blood Platelets
Chronic Renal Insufficiency
Bleeding Time
Anemia
Erythropoiesis
Therapeutics
Platelet Count
Platelet Aggregation
Arachidonic Acid
Tail
Thrombosis
Clinical Trials
Cytokines

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Use of Aspirin in normalization of recombinant human erythropoietin- mediated hyper-reactivity of platelets in rats. / Soni, Hiteshkumar; Vekaria, Amit M.; Rath, Akshyaya C.; Belemkar, Sateesh; Jain, Mukul R.

In: Indian Journal of Pharmacology, Vol. 46, No. 3, 01.01.2014, p. 328-333.

Research output: Contribution to journalArticle

Soni, Hiteshkumar ; Vekaria, Amit M. ; Rath, Akshyaya C. ; Belemkar, Sateesh ; Jain, Mukul R. / Use of Aspirin in normalization of recombinant human erythropoietin- mediated hyper-reactivity of platelets in rats. In: Indian Journal of Pharmacology. 2014 ; Vol. 46, No. 3. pp. 328-333.
@article{ebe2f4af459f4bbe94d3aa9b5641e0f0,
title = "Use of Aspirin in normalization of recombinant human erythropoietin- mediated hyper-reactivity of platelets in rats",
abstract = "Objectives: 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. Materials and 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.",
author = "Hiteshkumar Soni and Vekaria, {Amit M.} and Rath, {Akshyaya C.} and Sateesh Belemkar and Jain, {Mukul R.}",
year = "2014",
month = "1",
day = "1",
doi = "10.4103/0253-7613.132187",
language = "English (US)",
volume = "46",
pages = "328--333",
journal = "Indian Journal of Pharmacology",
issn = "0253-7613",
publisher = "Medknow Publications and Media Pvt. Ltd",
number = "3",

}

TY - JOUR

T1 - Use of Aspirin in normalization of recombinant human erythropoietin- mediated hyper-reactivity of platelets in rats

AU - Soni, Hiteshkumar

AU - Vekaria, Amit M.

AU - Rath, Akshyaya C.

AU - Belemkar, Sateesh

AU - Jain, Mukul R.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Objectives: 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. Materials and 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.

AB - Objectives: 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. Materials and 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.

UR - http://www.scopus.com/inward/record.url?scp=84901393842&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901393842&partnerID=8YFLogxK

U2 - 10.4103/0253-7613.132187

DO - 10.4103/0253-7613.132187

M3 - Article

VL - 46

SP - 328

EP - 333

JO - Indian Journal of Pharmacology

JF - Indian Journal of Pharmacology

SN - 0253-7613

IS - 3

ER -