How does warfarin exert its anti-coagulant effect (50% of marks)? Outline the pharmacology of the agents that can be used to reverse the effects of warfarin, giving examples (50% of marks).
Warfarin is a competitive inhibitor of the enzyme vitamin K epoxide reductase which converts oxidised or inactive vitamin K to reduced or active vitamin K Reduced vitamin K is required for the gamma carboxylation of the glutamate residues in the vitamin K dependant factors (II, VII, IX and X) and proteins C and S. This gamma carboxylation converts these clotting factors from their inactive to their active form resulting in coagulation. The presence of warfarin inhibits this conversion process resulting in anticoagulation. The presence of inactive
protein C and S explains the initial hypercoaguable effect of warfarin. The three main agents used to reverse the effects of warfarin are vitamin K, prothrombinex and fresh frozen plasma (FFP). It was expected answers would provide a brief overview of all three agents. Most candidates did not highlight the fact that parenteral vitamin K requires a few hours to work whereas prothombinex and FFP work immediately.
Better answers noted additional facts such as oral vitamin K because it is fat soluble requires the presence of bile salts to be absorbed from the gut or the rare but life threatening hypersensitivity reaction caused by intravenous vitamin K possibly related to its preservative benzyl alcohol. A common omission was the amount of coagulation factors in international units (IU) in an ampoule of prothormbinex or the dose required to reverse warfarin anticoagulation. A description of the clinical pros-cons of the various agents was not required to answer the
Mechanism of warfarin anticoagulation
Pharmacology of agents used to reverse
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Keller, Christina, Axel C. Matzdorff, and Bettina Kemkes-Matthes. "Pharmacology of warfarin and clinical implications." Seminars in thrombosis and hemostasis. Vol. 25. No. 01. Copyright© 1999 by Thieme Medical Publishers, Inc., 1999.
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