Anticoagulant Reversal Handbook - Page 9

Overview

PCC and reversal of oral anticoagulation

When faced with a patient with life-threatening bleeding , the anticoagulant effect needs to be reversed as soon as possible . The benefits of prothrombin complex concentrates are discussed
Alexandra Bucko Giorgia Saccullo MD Joost van Veen MD Mike Makris MA MB BS MD FRCP FRCPath Sheffield Haemophilia and Thrombosis Centre , Royal Hallamshire Hospital Sheffield , UK
Worldwide , an increasing number of patients are taking oral anticoagulants ; this is largely driven by the ageing population with increasing numbers of persons with atrial fibrillation , and for whom anticoagulation is the mainstay of treatment . Traditionally , warfarin has been the main anticoagulant used , but in the last five years , four direct-acting oral anticoagulants ( DOACs ) have been introduced . The currently licensed DOACs inhibit thrombin , in the case of dabigatran , or inhibit factor Xa , in the case of rivaroxaban , apixaban and edoxaban . Despite the rapid uptake of DOACs in many countries , warfarin remains the most commonly used oral anticoagulant worldwide .
Bleeding The most frequent adverse event of oral anticoagulant therapy is bleeding . In the case of warfarin , major bleeding requiring hospital admission occurs in 1 % per year , while fatal bleeding is observed in 0.3 % per year . 1 Overall the DOACs have the same number of bleeding complications as warfarin , but the distribution of bleeds is significantly different . DOACs are associated with fewer intracranial haemorrhages and more gastrointestinal bleeds . 2
“ In the case of warfarin , major bleeding requiring hospitalisation is observed in 1 % of patients per year ”
Reversal of bleeding Warfarin exerts its action by inhibiting the production of the active vitamin K-dependent clotting factors II , VII , IX and X , as well as protein C and protein S . Warfarin is monitored with the International normalised ratio ( INR ) test , with the majority of patients being maintained in the 2.0 – 3.0 range . As the INR increases , the risk of bleeding is also higher . 3 When faced with a patient with life-threatening bleeding , such as intracranial bleeding , the anticoagulant effect needs to be reversed as soon as possible . International recommendations for the management of this scenario suggest the use of 5 – 10mg of intravenous vitamin K and intravenous prothrombin complex concentrate ( PCC ). 3 When vitamin K is given intravenously , it significantly improves the coagulopathy within six to eight hours by allowing the production of active factors II , VII , IX and X . While waiting for the vitamin K effect , PCC is able to immediately replace the missing clotting factors . 1 PCCs contain factors II , IX , X and variable amounts of factor VII . Four-factor PCCs ( 4F-PCCs ) contain factor VII whereas 3F-PCCs do not . It is generally believed that 4F-PCC is more effective in reversing the warfarin anticoagulation ,
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