High-Dose Vitamin C Injection to Cancer Patients May Promote Thrombosis Through Procoagulant Activation of Erythrocytes.
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.
['Kim|Keunyoung|K|', 'Bae|Ok-Nam|ON|', 'Koh|Sung-Hee|SH|', 'Kang|Seojin|S|', 'Lim|Kyung-Min|KM|', 'Noh|Ji-Yoon|JY|', 'Shin|Sue|S|', 'Kim|Inho|I|', 'Chung|Jin-Ho|JH|']
D000255:Adenosine Triphosphate D000818:Animals D001205:Ascorbic Acid D001777:Blood Coagulation D002118:Calcium D004912:Erythrocytes D005434:Flow Cytometry D005978:Glutathione D006461:Hemolysis D006801:Humans D007275:Injections, Intravenous D007938:Leukemia D008297:Male D008855:Microscopy, Electron, Scanning D009369:Neoplasms D051381:Rats D017207:Rats, Sprague-Dawley D017382:Reactive Oxygen Species D013927:Thrombosis D014815:Vitamins
vitamin C cancer patient procoagulant activation red blood cells thrombotic risk