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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
- Authors
- Kim, Keunyoung; Chang, Youn-Kyeong; Bian, Yiying; Bae, Ok-Nam; Lim, Kyung-Min; Chung, Jin-Ho
- Ewha Authors
- 임경민
- SCOPUS Author ID
- 임경민
- Issue Date
- 2018
- Journal Title
- THROMBOSIS AND HAEMOSTASIS
- ISSN
- 0340-6245
2567-689X
- Citation
- THROMBOSIS AND HAEMOSTASIS vol. 118, no. 10, pp. 1765 - 1775
- Keywords
- paclitaxel; anti-cancer drug; thrombosis; red blood cells; phosphatidylserine exposure; microvesicle release
- Publisher
- GEORG THIEME VERLAG KG
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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.
- DOI
- 10.1055/s-0038-1670659
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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