2020A06Describe how the effects of warfarin can be reversed when URGENT surgery is indicated (40%).
For each option discuss the advantages and disadvantages (60%).

 

 

Intro:

Mechanism

·         Vitamin K epoxide reductase inhibitor

Factors affected

(half life)

·         Procoagulants: II (60h), VII (6h), IX (24h), X (36h)

·         Anticoagulants: protein C (8h), protein S (30h)

 

Reversal considerations:

Determinants

·         Urgency of surgery

·         Active bleeding

·         Degree of reversal required (e.g. neuraxial vs superficial)

Monitoring

·         INR is sensitive to factor VII (short t1/2) >> factor II (long t1/2)

·         Hence INR will normalise before coagulation is restored

·         Hence need INR ≤1.2 for safe neuraxial block after stopping warfarin
(source: ASRA guidelines)

 

Reversal options:

1.Expectant

·         i.e. drug washout -> regenerate Vit K -> regenerate clotting factors

·         t1/2β 40 hours -> offset in 5 days

·         ↑Duration if: Vit K deficient e.g. malnourished, CYP inhibitor (e.g. cimetidine), CYP competition e.g. amiodarone

·         ↓Duration if: CYP inducer (e.g. barbiturates)

·         Can operate immediately if a) low risk of bleeding b) benign consequences of bleeding c) easily compressible site

·         Pro: ↓risk thrombotic events, less disruptive to patient

·         Con: slow offset, ↑risk surgical bleeding

2.Vitamin K

·         i.e. replenish substrate -> regenerate clotting factors

·         PO 1-2mg for effect in 12-24 hours

·         IV 5-10mg for effect in 6-12 hours

·         Pro: fairly rapid reversal, obviates risks of blood products

·         Con: insufficient if very high INR or if active bleeding, difficult to restart warfarin after a big dose of Vitamin K

2.FFP

·         Contains all clotting factors

·         IV 15-30mL/kg (or 2-4mL/kg if with prothrombinex)

·         Also give Vit K to avoid rebound anticoagulation

·         Pro: immediate

·         Con: 15-30mL/kg = risk of TACO, risks of allogeneic transfusion

3.Prothrombinex

·         Contains factors 2, 9, 10

·         IV 25-50 units/kg

·         Also give Vit K to avoid re-bound anticoagulation

·         Pro: immediate, universally compatible

·         Con: factor 7 absent in Australian PCC

4.FEIBA

·         Contains active factor 7a, inactive factors 2,9,10

·         IV 50-100 units/kg

·         Also give Vit K to avoid rebound anticoagulation

·         Pro: contains all deficient coag factors

·         Con: less data for warfarin reversal

5.Novoseven

·         Activated Factor 7a

·         IV 50mcg/kg

·         Given in addition to FFP and/or prothrombinex

·         Only if persistent uncontrollable haemorrhage despite all other physiological, pharmacological and surgical efforts

·         Pro: immediate

·         Con: very expensive, short half life, high risk of thrombotic complications

 

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