Pro-Coagulant and Pro-Thrombotic Effects of Paclitaxel Mediated by Red Blood Cells
- 주제(키워드) paclitaxel , anti-cancer drug , thrombosis , red blood cells , phosphatidylserine exposure , microvesicle release
- 주제(기타) Hematology; Peripheral Vascular Disease
- 설명문(일반) [Kim, Keunyoung; Chang, Youn-Kyeong; Bian, Yiying; Chung, Jin-Ho] Seoul Natl Univ, Coll Pharm, Seoul, South Korea; [Bae, Ok-Nam] Hanyang Univ, Coll Pharm, Ansan, South Korea; [Lim, Kyung-Min] Ewha Womans Univ, Coll Pharm, Seoul, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 GEORG THIEME VERLAG KG
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000156633
- 본문언어 영어
- Published As http://dx.doi.org/10.1055/s-0038-1670659
초록/요약
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.
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