High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO)
High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO)
Date
2008
Authors
Kirkeby, Agnete
Torup, Lars
Bochsen, Louise
Kjalke, Marianne
Abel, Kristin
Theilgaard-Monch, Kim
Johansson, Pär I.
Bjørn, Søren E.
Gerwien, Jens
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Journal of the International Society on Thrombosis and Haemostasis ; 99 (2008), 4. - pp. 720-728. - ISSN 0340-6245
Abstract
The haematopoietic hormone erythropoietin (EPO) has neuroprotective properties and is currently being explored for treatment of stroke and other neurological disorders. Short-term, high-dose treatment with EPO seems to improve neurological function of stroke patients but may be associated with increased thrombotic risk, whereas alternative non-erythropoietic neuroprotective derivatives of EPO, such as carbamylated EPO (CEPO), may be devoid of such side-effects.We investigated the effects of short-term, high-dose treatment with EPO and CEPO on platelet function and haemostasis in healthy mice and rats. Animals received three daily doses of EPO or CEPO (50 μg/kg), and blood was compared with respect to alterations in haematology and platelet reactivity. In rats, treatment with EPO increased the haematocrit to >50% and the mean platelet volume by 37%,while CEPO had no effect on these parameters.Platelets from EPO-treated rats showed an increased sensitivity to thrombin receptor agonist peptides and elevated plasma levels of soluble P-selectin (sP-selectin) were found in treated mice. Further indicators of platelet hyperreactivity in EPO, but not CEPO-treated animals, were significantly increased aggregatory responses to collagen in whole blood and platelet-rich plasma (PRP).The increased platelet reactivity was paralleled by a decreased bleeding time after tail transection in rats. Samples from EPO-treated rats showed an attenuated response to ADP in whole blood aggregometry and thrombelastography (TEG) platelet mapping but not in apyrase-treated PRP, suggesting involvement of ADP receptor desensitization. These findings suggest that while EPO affects various aspects of platelet function, CEPO is devoid of such effects.
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570 Biosciences, Biology
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ADP,collagen,P-selectin,MPV,stroke
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KIRKEBY, Agnete, Lars TORUP, Louise BOCHSEN, Marianne KJALKE, Kristin ABEL, Kim THEILGAARD-MONCH, Pär I. JOHANSSON, Søren E. BJØRN, Jens GERWIEN, Marcel LEIST, 2008. High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO). In: Journal of the International Society on Thrombosis and Haemostasis. 99(4), pp. 720-728. ISSN 0340-6245. Available under: doi: 10.1160/TH07-03-0208BibTex
@article{Kirkeby2008Highd-7382, year={2008}, doi={10.1160/TH07-03-0208}, title={High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO)}, number={4}, volume={99}, issn={0340-6245}, journal={Journal of the International Society on Thrombosis and Haemostasis}, pages={720--728}, author={Kirkeby, Agnete and Torup, Lars and Bochsen, Louise and Kjalke, Marianne and Abel, Kristin and Theilgaard-Monch, Kim and Johansson, Pär I. and Bjørn, Søren E. and Gerwien, Jens and Leist, Marcel} }
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