High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO)
| Autor: | Louise Bochsen, Marcel Leist, Jens Gerwien, Lars Torup, Pär I. Johansson, Marianne Kjalke, Agnete Kirkeby, Kristin L. Abel, Kim Theilgaard-Mönch, Søren E. Bjørn |
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| Rok vydání: | 2008 |
| Předmět: |
ADP
collagen Male medicine.medical_specialty Bleeding Time P-selectin Platelet Aggregation Receptors Proteinase-Activated MPV Rats Sprague-Dawley Mice Bleeding time Internal medicine hemic and lymphatic diseases ddc:570 medicine Animals Platelet Mean platelet volume Erythropoietin Whole blood Hematology medicine.diagnostic_test Dose-Response Relationship Drug business.industry Blood Proteins Platelet Activation stroke Recombinant Proteins Rats Adenosine Diphosphate P-Selectin Endocrinology Neuroprotective Agents Hemostasis Immunology Collagen business medicine.drug |
| Zdroj: | University of Copenhagen |
| ISSN: | 0340-6245 |
| Popis: | SummaryThe 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. |
| Databáze: | OpenAIRE |
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