Anticoagulant Reversal Handbook - Page 5

Overview

Bleeding management and VKAs : an overview

Bleeding is a common , and sometimes serious or life-threatening , complication of anticoagulation therapy , particularly with the vitamin K antagonists , and an introduction to bleeding management is given here
Caroline Bsirini MD Majed A Refaai MD Department of Pathology and Laboratory Medicine , University of Rochester Medical Center , Rochester , New York , USA
Warfarin ( VKAs )
Vitamin K hydroquinone
Inactive proteins factors II , VIII , IX , X proteins C , S , and Z
Vitamin K antagonists ( VKAs ; for example , warfarin ) are some of the most prescribed drugs worldwide . VKAs were first introduced in the early 1950s as an effective and relatively safe drug for the prevention of thrombosis and thromboembolism . 1 , 2 Nowadays , and despite the broad introduction of the new oral anticoagulants , VKAs are still among the most used anticoagulants . VKAs are used in a variety of clinical settings , including primary and secondary prevention of venous thromboembolism ( VTE ) and pulmonary embolism ( PE ), prevention of systemic embolism in patients with atrial fibrillation and prosthetic heart valves , as well as in antiphospholipid syndrome and inherited thrombophilia , such as factor V Leiden thrombophilia , deficiencies of antithrombin III , protein C , or protein S . 3
Mode of action VKAs exert their effects by inhibiting vitamin K epoxide reductase and blocking the γ-carboxylation of several glutamate residues in the vitamin K-dependent factors ( that is , factors II , VII , IX , and X ) as well as the endogenous anticoagulant proteins C and S resulting in biologically inactive factors ( Figure 1 ). Thus , the anticoagulant activity of VKA depends on the clearance of these clotting factors from the systemic circulation once the drug is administered .
Warfarin ( VKAs )
Vitamin K
Vitamin K epoxide reductase
Figure 1 : Action of VKA ( warfarin ) on vitamin K cycle and clotting protein activation . 26
“ VKAs exert their effects by inhibiting vitamin K epoxide reductase and blocking the carboxylation of glutamate residues in the vitamin K-dependent clotting factors ”
Challenges in VKA therapy Some of the major challenges in VKA therapy are drug – drug and food – drug interactions that significantly impact its anticoagulation effect . 1 , 2 Therefore , monitoring VKA therapy is essential due to the associated high risk of thrombosis or bleeding . The International normalised ratio ( INR ), which is a calculation based on prothrombin time ( PT ), is the monitoring indicator for VKA therapy . The earliest changes in INR are often seen within 24 – 36 hours of VKA administration ; however , the antithrombotic effect is usually detected
Vitamin K-dependent carboxylase
Activated proteins
within approximately five days ( dependent on the clearance of prothrombin ). Hence , a bridge therapy with unfractionated heparin ( UFH ) or low molecular weight heparin ( LMWH ) is often required at VKA therapy initiation for approximately four to five days in patients with an active hypercoagulable state . 4 Once INR approaches an acceptable therapeutic range for at least two consecutive days , heparin therapy is discontinued . 3 , 4 INR should then be checked periodically to maintain a proper therapeutic range . The most common reasons for unexpected fluctuations of
3 www . hospitalpharmacyeurope . com