Vitamin K counteracts the effect of warfarin in liver but not in bone

Thromb Res. 1987 Apr 1;46(1):121-31. doi: 10.1016/0049-3848(87)90212-x.

Abstract

Treatment with high dosages of Vitamin K completely inhibited the effect of Warfarin on blood coagulation but had essentially no ability to counteract the effect of Warfarin on the gamma-carboxylation of bone G1a protein (BGP; osteocalcin). Provided that rats received the appropriate dosage of Vitamin K prior to and concurrent with the administration of Warfarin, daily dosages as high as 7.7 mg Warfarin per 100 g body weight had no effect on blood coagulation times. This Warfarin dosage is approximately 150 times higher than the 50 micrograms per 100 g body weight which caused coagulation times to double in rats which did not receive Vitamin K. In dramatic contrast, the dosage of Warfarin required to reduce the gamma-carboxylation status of BGP to one-half normal, 30 micrograms per 100 g body weight, was essentially unaffected by Vitamin K treatment. These results indicate the existence of a major difference between the metabolism of Vitamin K by the hepatocytes which synthesize coagulation factors and the osteoblasts which synthesize BGP. The practical consequence of this difference is that it is now possible to antagonize the action of Vitamin K in osteoblasts, as well as in other cells which have the same Vitamin K metabolism, without affecting blood coagulation times.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Coagulation / drug effects
  • Bone and Bones / drug effects*
  • Calcium-Binding Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Liver / drug effects*
  • Osteocalcin
  • Partial Thromboplastin Time
  • Prothrombin Time
  • Rats
  • Vitamin K / pharmacology*
  • Warfarin / antagonists & inhibitors*

Substances

  • Calcium-Binding Proteins
  • Osteocalcin
  • Vitamin K
  • Warfarin