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High-Dose Vitamin C Injection to Cancer Patients May Promote Thrombosis Through Procoagulant Activation of Erythrocytes

Title
High-Dose Vitamin C Injection to Cancer Patients May Promote Thrombosis Through Procoagulant Activation of Erythrocytes
Author
배옥남
Keywords
vitamin C; thrombotic risk; red blood cells; procoagulant activation; cancer patient; MICROVASCULAR ENDOTHELIAL-CELLS; I CLINICAL-TRIAL; ASCORBIC-ACID; PHOSPHATIDYLSERINE EXPOSURE; VENOUS THROMBOEMBOLISM; HYDROGEN-PEROXIDE; PHOSPHOLIPASE-D; IRON UPTAKE; DISEASE; PHARMACOKINETICS
Issue Date
2015-10
Publisher
OXFORD UNIV PRESS
Citation
TOXICOLOGICAL SCIENCES, v. 147, No. 2, Page. 350-359
Abstract
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.
URI
https://academic.oup.com/toxsci/article/147/2/350/1620914http://hdl.handle.net/20.500.11754/40562
ISSN
1096-6080; 1096-0929
DOI
10.1093/toxsci/kfv133
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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