抗凝治疗和临床麻醉__培训课件.ppt

* * * Warfarin inhibits the synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S. Specifically, warfarin interferes with the cyclic interconversion of vitamin K and its 2,3 epoxide (vitamin K epoxide). Vitamin K is a cofactor for the carboxylation of glutamate residues to gamma-carboxyglutamates on the N-terminal regions of vitamin K-dependent proteins. Carboxylation allows the coagulation proteins to undergo a conformational change which is necessary for their activation. Warfarin exerts its anticoagulant effect by inhibiting vitamin K epoxide reductase and possibly vitamin K reductase. This results in depletion of the reduced form of vitamin K (vitamin KH2) and limits the gamma-carboxylation of the vitamin K-dependent coagulant proteins. The degree of effect on the vitamin K-dependent proteins is dependent upon the dose of warfarin. The anticoagulant effects of warfarin are stereoselective; the S-isomer of warfarin is 3—5 times more potent than the R-isomer. Therapeutic doses of warfarin decrease the total amount of active vitamin K-dependent clotting factors produced by the liver by 30—50%. * Phytonadione, or vitamin K1, is a synthetic compound that is chemically indistinguishable from naturally occurring vitamin K1. Vitamin K is found in both plant and animal sources, and is also produced by intestinal bacteria; however, vitamin K from these different sources is not identical. is found in plants and is the only natural vitamin K available for therapeutic use. Menaquinones (vitamin K2) are a series of compounds that can be synthesized by bacteria. For the treatment of hemorrhage or bleeding prophylaxis:?in patients with hypoprothrombinemia secondary to warfarin therapy:NOTE: The following recommendations were obtained from the Fifth ACCP Consensus Conference on Antithrombotic Therapy.1last=7/17/00#166[2023] Although doses = 10 mg of vitamin K1 are effective, use of large doses can lead to warfarin resistanc