High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO).

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

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 tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Kirkeby, A, Torup, L, Bochsen, L, Kjalke, M, Abel, K, Theilgaard-Mønch, K, Johansson, PI, Bjørn, SE, Gerwien, J & Leist, M 2008, 'High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO).', Thrombosis and Haemostasis, bind 99, nr. 4, s. 720-8.

APA

Kirkeby, A., Torup, L., Bochsen, L., Kjalke, M., Abel, K., Theilgaard-Mønch, K., Johansson, P. I., Bjørn, S. E., Gerwien, J., & Leist, M. (2008). High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO). Thrombosis and Haemostasis, 99(4), 720-8.

Vancouver

Kirkeby A, Torup L, Bochsen L, Kjalke M, Abel K, Theilgaard-Mønch K o.a. High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO). Thrombosis and Haemostasis. 2008;99(4):720-8.

Author

Kirkeby, Agnete ; Torup, Lars ; Bochsen, Louise ; Kjalke, Marianne ; Abel, Kristin ; Theilgaard-Mønch, Kim ; Johansson, Pär I ; Bjørn, Søren E ; Gerwien, Jens ; Leist, Marcel. / High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO). I: Thrombosis and Haemostasis. 2008 ; Bind 99, Nr. 4. s. 720-8.

Bibtex

@article{1bfec93058aa11dd8d9f000ea68e967b,
title = "High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO).",
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 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.",
author = "Agnete Kirkeby and Lars Torup and Louise Bochsen and Marianne Kjalke and Kristin Abel and Kim Theilgaard-M{\o}nch and Johansson, {P{\"a}r I} and Bj{\o}rn, {S{\o}ren E} and Jens Gerwien and Marcel Leist",
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-Activated",
year = "2008",
language = "English",
volume = "99",
pages = "720--8",
journal = "Thrombosis et diathesis haemorrhagica",
issn = "0340-6245",
publisher = "Schattauer",
number = "4",

}

RIS

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 -

ID: 5142656