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

Keunyoung Kim, Youn Kyeong Chang, Yiying Bian, Ok Nam Bae, Kyung Min Lim, Jin Ho Chung

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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)ζ 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 PKCζ 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 and MV release, which can ultimately promote thrombus formation.

Original languageEnglish
Article number180180
Pages (from-to)1765-1775
Number of pages11
JournalThrombosis and Haemostasis
Volume118
Issue number10
DOIs
StatePublished - 2018

Keywords

  • anti-cancer drug
  • microvesicle release
  • paclitaxel
  • phosphatidylserine exposure
  • red blood cells
  • thrombosis

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