Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Thrombosis and Haemostasis |
| Vol/bind | 99 |
| Udgave nummer | 4 |
| Sider (fra-til) | 720-8 |
| Antal sider | 8 |
| ISSN | 0340-6245 |
| Status | Udgivet - 2008 |
Bibliografisk note
Keywords: Adenosine Diphosphate; Animals; Bleeding Time; Blood Proteins; Collagen; Dose-Response Relationship, Drug; Erythropoietin; Erythropoietin, Recombinant; Male; Mice; Neuroprotective Agents; P-Selectin; Platelet Activation; Platelet Aggregation; Rats; Rats, Sprague-Dawley; Receptors, Proteinase-ActivatedCitationsformater
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High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO). / Kirkeby, Agnete; Torup, Lars; Bochsen, Louise; Kjalke, Marianne; Abel, Kristin; Theilgaard-Mønch, Kim; Johansson, Pär I; Bjørn, Søren E; Gerwien, Jens; Leist, Marcel.
I: Thrombosis and Haemostasis, Bind 99, Nr. 4, 2008, s. 720-8.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO).
AU - Kirkeby, Agnete
AU - Torup, Lars
AU - Bochsen, Louise
AU - Kjalke, Marianne
AU - Abel, Kristin
AU - Theilgaard-Mønch, Kim
AU - Johansson, Pär I
AU - Bjørn, Søren E
AU - Gerwien, Jens
AU - Leist, Marcel
N1 - Keywords: Adenosine Diphosphate; Animals; Bleeding Time; Blood Proteins; Collagen; Dose-Response Relationship, Drug; Erythropoietin; Erythropoietin, Recombinant; Male; Mice; Neuroprotective Agents; P-Selectin; Platelet Activation; Platelet Aggregation; Rats; Rats, Sprague-Dawley; Receptors, Proteinase-Activated
PY - 2008
Y1 - 2008
N2 - 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 microg/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.
AB - 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 microg/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.
M3 - Journal article
C2 - 18392330
VL - 99
SP - 720
EP - 728
JO - Thrombosis et diathesis haemorrhagica
JF - Thrombosis et diathesis haemorrhagica
SN - 0340-6245
IS - 4
ER -