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Pro-Coagulant and Pro-Thrombotic Effects of Paclitaxel Mediated by Red Blood Cells.

Title
Pro-Coagulant and Pro-Thrombotic Effects of Paclitaxel Mediated by Red Blood Cells.
Author
배옥남
Keywords
paclitaxel; anti-cancer drug; thrombosis; red blood cells; phosphatidylserine exposure; microvesicle release
Issue Date
2018-09
Publisher
WILEY
Citation
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, v. 118, No. 10, Page. 1765-1775
Abstract
Background Paclitaxel is one of the most widely used anti-cancer drugs, but numerous case reports of thrombotic events in the cancer patients using paclitaxel raise concern over its pro-thrombotic risk. Materials and Methods We investigated whether paclitaxel can elicit pro-thrombotic properties in red blood cells (RBCs) through phosphatidylserine (PS) exposure and microvesicle (MV) release. Results In freshly isolated human RBCs, paclitaxel induced thrombin generation through PS exposure and MV release, whereas either coagulation factors or platelets were unaffected. Paclitaxel-induced PS exposure in RBC was mediated by scramblase activation which was induced by calcium-independent protein kinase C (PKC). activation. Paclitaxel also increased RBC-endothelial cell adhesion and RBC aggregate formation which can also contribute to thrombosis. Indeed, intravenous administration of paclitaxel to rats induced PS exposure and PKC. activation in RBCs in vivo which ultimately promoted venous thrombus formation. Conclusion These results demonstrated that paclitaxel may elicit pro-thrombotic properties in RBCs through PS exposure andMV release, which can ultimately promote thrombus formation.
URI
https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0038-1670659http://repository.hanyang.ac.kr/handle/20.500.11754/106171
ISSN
0340-6245; 2567-689X
DOI
10.1055/s-0038-1670659
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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