@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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    <dc:contributor>Abel, Kristin</dc:contributor>
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    <dc:creator>Kirkeby, Agnete</dc:creator>
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    <dc:contributor>Kjalke, Marianne</dc:contributor>
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    <dcterms:issued>2008</dcterms:issued>
    <dcterms:title>High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO)</dcterms:title>
    <dc:contributor>Johansson, Pär I.</dc:contributor>
    <dc:contributor>Leist, Marcel</dc:contributor>
    <dcterms:abstract xml:lang="eng">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 &gt;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.</dcterms:abstract>
    <dc:contributor>Bochsen, Louise</dc:contributor>
    <dc:contributor>Kirkeby, Agnete</dc:contributor>
    <dc:contributor>Bjørn, Søren E.</dc:contributor>
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    <dc:creator>Theilgaard-Monch, Kim</dc:creator>
    <dc:creator>Gerwien, Jens</dc:creator>
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    <dcterms:bibliographicCitation>First publ. in: Journal of the International Society on Thrombosis and Haemostasis ; 99 (2008). - pp. 720-728</dcterms:bibliographicCitation>
    <dc:creator>Kjalke, Marianne</dc:creator>
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    <dc:contributor>Torup, Lars</dc:contributor>
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    <dc:contributor>Gerwien, Jens</dc:contributor>
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    <dc:creator>Leist, Marcel</dc:creator>
    <dc:creator>Johansson, Pär I.</dc:creator>
    <dc:creator>Bjørn, Søren E.</dc:creator>
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    <dc:language>eng</dc:language>
    <dc:creator>Torup, Lars</dc:creator>
    <dc:contributor>Theilgaard-Monch, Kim</dc:contributor>
    <dc:creator>Abel, Kristin</dc:creator>
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