title: High-Dose Vitamin C Injection to Cancer Patients May Promote Thrombosis Through Procoagulant Activation of Erythrocytes.
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 (0.5-5 mM) 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.
authors.affiliation: *College of Pharmacy, Seoul National University, Seoul 151-742, Korea;
authors.forename: Keunyoung
authors.initials: K
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Hanyang University, Ansan 426-791, Korea;
authors.forename: Ok-Nam
authors.initials: ON
authors.lastname: Bae
authors.affiliation: *College of Pharmacy, Seoul National University, Seoul 151-742, Korea;
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Koh
authors.affiliation: *College of Pharmacy, Seoul National University, Seoul 151-742, Korea;
authors.forename: Seojin
authors.initials: S
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Ewha Womans Universtiy, Seoul 120-750, Korea;
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lim
authors.affiliation: *College of Pharmacy, Seoul National University, Seoul 151-742, Korea;
authors.forename: Ji-Yoon
authors.initials: JY
authors.lastname: Noh
authors.affiliation: Department of Laboratory Medicine, Boramae Hospital, Seoul 156-707, Korea; and.
authors.forename: Sue
authors.initials: S
authors.lastname: Shin
authors.affiliation: College of Medicine, Seoul National University, Seoul 110-799, Korea.
authors.forename: Inho
authors.initials: I
authors.lastname: Kim
authors.affiliation: *College of Pharmacy, Seoul National University, Seoul 151-742, Korea;
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood; D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects*; D005434:Flow Cytometry; D005978:Glutathione / Q000097:blood; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D007938:Leukemia / Q000097:blood / Q000188:drug therapy; D008297:Male; D008855:Microscopy, Electron, Scanning; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000097:blood; D013927:Thrombosis / Q000139:chemically induced*; D014815:Vitamins / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood
chemical_list: D017382:Reactive Oxygen Species; D014815:Vitamins; D000255:Adenosine Triphosphate; D005978:Glutathione; D001205:Ascorbic Acid; D002118:Calcium
keywords: cancer patient; procoagulant activation; red blood cells; thrombotic risk; vitamin C