General principles for General principles for preventing high INRpreventing high INR Simple dental or dermatological procedures may Simple dental or dermatological procedures may

not require interruption to warfarin therapy.not require interruption to warfarin therapy. If necessary, warfarin therapy can be withheld 5 If necessary, warfarin therapy can be withheld 5

days before elective surgery, when the INR usually days before elective surgery, when the INR usually falls to below 1.5 and surgery can be conducted falls to below 1.5 and surgery can be conducted safely. safely.

General principles for preventing high INRGeneral principles for preventing high INR • • Avoid high loading doses of warfarin, Avoid high loading doses of warfarin, • • Potential warfarin–drug interactions need to be Potential warfarin–drug interactions need to be

considered.considered. • • Aim for an INR level that balances the Aim for an INR level that balances the

therapeutic goal with risk factors of bleeding on an therapeutic goal with risk factors of bleeding on an individual basis. individual basis.

• • Avoid frequent dose adjustments. Avoid frequent dose adjustments. • • Avoid excessive increases in dose when INR Avoid excessive increases in dose when INR

drifts below target INR range.drifts below target INR range.

Dramatic increase in number of patients Dramatic increase in number of patients receiving OACreceiving OAC

Interindividual variation (environmental and Interindividual variation (environmental and genetic) genetic)

Incidence of warfarin associated Incidence of warfarin associated haemorrhage :fatal haemorrhage 1%/Y. haemorrhage :fatal haemorrhage 1%/Y.

Reversal :seriousness of bleeding ,balance Reversal :seriousness of bleeding ,balance against thrombotic risk and speed and against thrombotic risk and speed and completeness of reversalcompleteness of reversal

Options include simple dose omission ,vitamin Options include simple dose omission ,vitamin K & factors replacement K & factors replacement

FFP is less effective in correction of FFP is less effective in correction of coagulopathy ,volume overload & slow infusion coagulopathy ,volume overload & slow infusion rate than PCCs rate than PCCs

PCCs are also subjected to virus inactivation PCCs are also subjected to virus inactivation

PCCsPCCs

PCCs are intermediate purity pooled plasma PCCs are intermediate purity pooled plasma products products

only HTDEFIX is licensed in UK for warfarin reversalonly HTDEFIX is licensed in UK for warfarin reversal PCCs, (‘‘four factor concentrates’’), OR low VII PCCs, (‘‘four factor concentrates’’), OR low VII

(three) (three) Amounts of protein C and SAmounts 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 INR 2–3.9, 25 U/kg; INR 4–5.9, 35 U/kg; INR . 6, 50

U/kg. U/kg. Thrombogenicity, exacerbation of DIC are dose Thrombogenicity, exacerbation of DIC are dose

related problems,related problems,

The current cost in the UK is around 25 pence/unit The current cost in the UK is around 25 pence/unit (total cost for a single treatment for a 70 kg (total cost for a single treatment for a 70 kg individual £437 -£875. individual £437 -£875.

More expensive than the cost of FFP. ( unit of More expensive than the cost of FFP. ( unit of produced from UK plasma currently costs about produced from UK plasma currently costs about £30). £30).

FFP that is methylene blue treated or produced from FFP that is methylene blue treated or produced from non-UK plasma is more expensive.) non-UK plasma is more expensive.)

On the basis of the current evidence, a PCC plus IV On the basis of the current evidence, a PCC plus IV vitamin K is the treatment of choice for patients with vitamin K is the treatment of choice for patients with major haemorrhage.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 Combination of PCC and FFP covers period before

vitamin K1 has reached its full effect.vitamin K1 has reached its full effect. Vitamin K1 is essential for sustaining the reversal Vitamin K1 is essential for sustaining the reversal

achieved achieved Pre- and postoperative management of Pre- and postoperative management of

anticoagulationanticoagulation. bridging therapy. . bridging therapy. Prolonged immobility ,AF index event requiring Prolonged immobility ,AF index event requiring

anticoagulation occurred more than 3 months anticoagulation occurred more than 3 months prosthetic valves VTE within the preceding 3 months prosthetic valves VTE within the preceding 3 months

Unfractionated heparin 24 hours preceding surgery Unfractionated heparin 24 hours preceding surgery