The effect of intravenous vitamin E and menadiol sodium diphosphate on vitamin K dependent clotting factors

During a Phase I study of intravenous vitamin E-free alcohol (all-rac-alpha-tocopherol or Ephynal) in patients with neuroblastoma, we noticed a bleeding diathesis in two patients receiving 2300 mg/m2 daily for four or more days in succession. Both blood prothrombin time and accelerated partial thromboplastin times were prolonged. These spontaneously returned to normal levels three days after interrupting vitamin E infusions. It was also noted that factors VII, IX and X were decreased, which corresponded with the prolonged PT and APTT. It was found that by infusing menadiol sodium diphosphate just prior to the vitamin E, these inhibiting effects on procoagulant factors could be abrogated and high dosages of vitamin E-free alcohol safely given.