High-dose vitamin C injection to cancer patients may promote thrombosis through procoagulant activation of erythrocytes

Keunyoung Kim, Ok Nam Bae, Sung Hee Koh, Seojin Kang, Kyung Min Lim, Ji Yoon Noh, Sue Shin, Inho Kim, Jin Ho Chung

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Potential risk of high-dose vitamin C consumption is often ignored. Recently, gram-dose vitamin C is being intravenously injected for the treatment of cancer, which can expose circulating blood cells to extremely high concentrations of vitamin C. As well as platelets, red blood cells (RBCs) can actively participate in thrombosis through procoagulant activation. Here, we examined the procoagulant and prothrombotic risks associated with the intravenous injection of gram-dose vitamin C. Vitamin C (0.5-5mM) increased procoagulant activity of freshly isolated human RBCs via the externalization of phosphatidylserine (PS) to outer cellular membrane and the formation of PS-bearing microvesicles. PS exposure was induced by the dysregulation of key enzymes for the maintenance of membrane phospholipid asymmetry, which was from vitamin C-induced oxidative stress, and resultant disruption of calcium and thiol homeostasis. Indeed, the intravenous injection of vitamin C (0.5-1.0 g/kg) in rats in vivo significantly increased thrombosis. Notably, the prothrombotic effects of vitamin C were more prominent in RBCs isolated from cancer patients, who are at increased risks of thrombotic events. Vitamin C-induced procoagulant and prothrombotic activation of RBCs, and increased thrombosis in vivo. RBCs from cancer patients exhibited increased sensitivity to the prothrombotic effects of vitamin C, reflecting that intravenous gram-dose vitamin C therapy needs to be carefully revisited.

Original languageEnglish
Pages (from-to)350-359
Number of pages10
JournalToxicological Sciences
Issue number2
StatePublished - Oct 2015

Bibliographical note

Publisher Copyright:
© The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.


  • Cancer patient
  • Procoagulant activation
  • Red blood cells
  • Thrombotic risk
  • Vitamin C


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