5. General principles for preventing high INR Simple dental or dermatological procedures may not require interruption to warfarin therapy. Simple dental or dermatological procedures may not require interruption to warfarin therapy. If necessary, warfarin therapy can be withheld 5 days before elective surgery, when the INR usually falls to below 1.5 and surgery can be conducted safely. If necessary, warfarin therapy can be withheld 5 days before elective surgery, when the INR usually falls to below 1.5 and surgery can be conducted safely. General principles for preventing high INR General principles for preventing high INR Avoid high loading doses of warfarin, Avoid high loading doses of warfarin, Potential warfarin–drug interactions need to be considered. Potential warfarin–drug interactions need to be considered. Aim for an INR level that balances the therapeutic goal with risk factors of bleeding on an individual basis. Aim for an INR level that balances the therapeutic goal with risk factors of bleeding on an individual basis. Avoid frequent dose adjustments. Avoid frequent dose adjustments. Avoid excessive increases in dose when INR drifts below target INR range. Avoid excessive increases in dose when INR drifts below target INR range.

9. Dramatic increase in number of patients receiving OAC Dramatic increase in number of patients receiving OAC Interindividual variation (environmental and genetic) Interindividual variation (environmental and genetic) Incidence of warfarin associated haemorrhage :fatal haemorrhage 1%/Y. Incidence of warfarin associated haemorrhage :fatal haemorrhage 1%/Y. Reversal :seriousness of bleeding,balance against thrombotic risk and speed and completeness of reversal Reversal :seriousness of bleeding,balance against thrombotic risk and speed and completeness of reversal Options include simple dose omission,vitamin K & factors replacement Options include simple dose omission,vitamin K & factors replacement FFP is less effective in correction of coagulopathy,volume overload & slow infusion rate than PCCs FFP is less effective in correction of coagulopathy,volume overload & slow infusion rate than PCCs PCCs are also subjected to virus inactivation PCCs are also subjected to virus inactivation

16. PCCs PCCs are intermediate purity pooled plasma products PCCs are intermediate purity pooled plasma products only HTDEFIX is licensed in UK for warfarin reversal only HTDEFIX is licensed in UK for warfarin reversal PCCs, (‘‘four factor concentrates’’), OR low VII (three) PCCs, (‘‘four factor concentrates’’), OR low VII (three) Amounts of protein C and S Amounts of protein C and S Optimum dose not established. Optimum dose not established. INR 2–3.9, 25 U/kg; INR 4–5.9, 35 U/kg; INR. 6, 50 U/kg. INR 2–3.9, 25 U/kg; INR 4–5.9, 35 U/kg; INR. 6, 50 U/kg. Thrombogenicity, exacerbation of DIC are dose related problems, Thrombogenicity, exacerbation of DIC are dose related problems, The current cost in the UK is around 25 pence/unit (total cost for a single treatment for a 70 kg individual £437 -£875. The current cost in the UK is around 25 pence/unit (total cost for a single treatment for a 70 kg individual £437 -£875. More expensive than the cost of FFP. ( unit of produced from UK plasma currently costs about £30). More expensive than the cost of FFP. ( unit of produced from UK plasma currently costs about £30). FFP that is methylene blue treated or produced from non-UK plasma is more expensive.) FFP that is methylene blue treated or produced from non-UK plasma is more expensive.)

17. On the basis of the current evidence, a PCC plus IV vitamin K is the treatment of choice for patients with major haemorrhage. On the basis of the current evidence, a PCC plus IV vitamin K is the treatment of choice for patients with major haemorrhage. A dose of 30 U/kg (regardless of INR) A dose of 30 U/kg (regardless of INR) Combination of PCC and FFP covers period before vitamin K1 has reached its full effect. Combination of PCC and FFP covers period before vitamin K1 has reached its full effect. Vitamin K1 is essential for sustaining the reversal achieved Vitamin K1 is essential for sustaining the reversal achieved Pre- and postoperative management of anticoagulation. bridging therapy. Pre- and postoperative management of anticoagulation. bridging therapy. Prolonged immobility,AF index event requiring anticoagulation occurred more than 3 months prosthetic valves VTE within the preceding 3 months Prolonged immobility,AF index event requiring anticoagulation occurred more than 3 months prosthetic valves VTE within the preceding 3 months Unfractionated heparin 24 hours preceding surgery Unfractionated heparin 24 hours preceding surgery