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(Stroke. 2009;40:656.)
© 2009 American Heart Association, Inc.

Research Letters

Vitamin E Suppresses Enhancement of Factor VIII-Dependent Thrombin Generation by Systemic Hypoxia

Jong-Shyan Wang, PhD; Mei-Ling Cheng, PhD; Hsiu-Chuan Yen, PhD; Bih-Show Lou, PhD Huang-Chun Liu, MS

From the Graduate Institute of Rehabilitation Science and Center for Healthy Aging Research (J.-S.W., H.-C.L.), the Graduate Institute of Medical Biotechnology (M.-L.C., H.-C.Y.), and the General Education Center (B.-S.L.), Chang Gung University, Tao-Yuan, Taiwan.

Correspondence to Jong-Shyan Wang, PhD, Graduate Institute of Rehabilitation Science, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, 333, Taiwan. E-mail s5492{at}mail.cgu.edu.tw

Background and Purpose— Increased thrombin activity is an essential component of hemostatic reactions. This study elucidates how various hypoxic interventions impact endogenous thrombin generation (TG) after treatment with/without lipophilic antioxidant vitamin E.

Methods— Twenty-four healthy sedentary men were randomly assigned to vitamin E (n=12) and placebo (n=12) groups. These subjects were randomly exposed to 12% (severe hypoxia), 15% (moderate hypoxia), 18% (light hypoxia), and 21% (normoxia) O₂ for 2 hours in a normobaric hypoxia chamber. A novel calibrated, automated thrombinography approach was used to measure TG in plasma.

Results— In the placebo group, severe hypoxia enhanced plasma FVIII level/activity and TG, which was accompanied by increased urinary 15-F2t-8-isoprostane level and decreased plasma total antioxidant content and superoxide dismutase activity. However, depletion of FVIII by incubation with anti-FVIII antibodies in plasma suppressed enhancement of TG by severe hypoxia. After administration of 1000 IU vitamin E, severe hypoxia did not significantly alter urinary 15-F_2t-8-isoprostane level and plasma total antioxidant content, superoxide dismutase activity, FVIII level/activity, or TG. Moreover, redox status, FVIII level/activity, and TG were constant in response to moderate hypoxia, light hypoxia, and normoxia in the placebo and vitamin E groups.

Conclusion— We conclude that severe hypoxia promotes FVIII-dependent TG, likely by elevating oxidative stress; this hypoxic effect was ameliorated by pretreatment with vitamin E.

Key Words: coagulation • oxygen • tocopherol

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