Audit of warfarin reversal in over-anticoagulated patients D Wright and J Seal Department of Haematology Pontefract General Infirmary Nov 2002

Bleeding during warfarin therapy Risk factors Age High target INR Actual INR PMH of bleeding CVA Hypertension Alcohol/liver disease

Risk of bleeding whilst on warfarin ISCOAT study Prospective study of 2745 patients Bleeding complications: All 7.6 per 100 patient years Major 1.1 per 100 patient years Fatal cerebral bleeds 0.25 per 100 patient years Age > 70 : 10.5 per 100 patient years < 70 : 6 per 100 patient years

Risk of bleeding whilst on oral anticoagulation ISCOAT study: Lancet 1996

Aim of study Establish a baseline audit of historical practice of warfarin omission in patients with INR>8 Assess feasibility of using oral vitamin K to reverse anticoagulation in patients with INR>8

Methods Patients attend community phlebotomy clinics for venous blood sampling. At this visit patient completes a record sheet detailing warfarin dose, change in medication, clinical condition and any bleeding symptoms. Samples are sent to central lab for INR testing, along with record sheet. Results are downloaded to A/C computer. BMS reviews results.

INR Advice Given InclusiveMiss 3 days.Repeat INR In 1 week. Reduce Dose InclusiveMiss 3 days. Repeat INR in 3 days. No dose given. See High INR policy. 8.1 and aboveUnable to calculate dose See High INR policy

INR OVER 8.0 Significant bleeding symptoms – refer to A/E No Bleeding – inform Clinical Haematologist Give 2mg oral dose Vitamin K (KONAKION) See separate SOP for prescription Warfarin discontinued temporarily

INR OVER 8.0 Arrange for INR next day. Repeat INR daily until INR <6.0 If INR remains over 8.0 repeat Vitamin K If patient unable to receive Vitamin K discontinue for 3 days and re-check INR Complete a case report Send a fax to inform GP

INR 7.1 – 8.0 Significant bleeding symptoms – refer to A/E No bleeding proceed as follows Stop Warfarin for 3 days and re-check INR Advise patient to attend A/E if bleeding develops

INR 7.1 – 8.0 Send a fax to inform GP Recommence warfarin when INR is back in the therapeutic range Complete a case report

Restarting Warfarin If over anticoagulation is clearly secondary to a transient event, which has now resolved, then restart Warfarin at the previous maintenance dose If the reason for over anticoagulation is unknown or due to a continuing risk factor, then restart at a dose between 20% and 25% less than the previous maintenance dose

Results Between Feb - Dec 2001 forty-one patients had an INR>8 in the absence of significant bleeding 20 received oral vitamin K 21 were managed by Warfarin omission

Vitamin K (n=20) Warfarin omission (n=21) Age:Mean6867 Range Duration of therapy: Median4.8yrs5yrs Range Baseline INR: Mean Range Characteristics of high INR patients

Vitamin KWarfarin omission AF812 DVT/PE64 Mechanical valve 35 PVD30 Indications for warfarin therapy

Causes of over-anticoagulation Vitamin K group (n=20) Warfarin omission group (n=21) Wrong dose36 Interacting medication 22 Alcohol excess 30 Unknown1213

Vitamin K (n=20) Warfarin omission (n=21) 1 st follow up INR: Mean Range No with INR> No with INR >8.022 No with INR< st follow up INR

Vitamin KWarfarin omission Day 7 INR Mean Range No with INR> No with INR<2.0 58

Clinical events One patient from each group admitted with bleeding complications One patient in warfarin omission group had a breakthrough PE

Conclusions After omitting warfarin in patients with an INR>8, 50% still had a raised INR after 3 days Oral vitamin K at a 2 mg dose achieved at least comparable results within 24 hours Both patient groups had unstable INR control for at least 1 week after the event Use of oral vitamin K was not associated with warfarin resistance