2020A Question 06
Describe how the effects of warfarin can be reversed when URGENT surgery is indicated (40%). For each option discuss the advantages and disadvantages (60%).
Examiner Report
To pass, candidates needed to demonstrate an understanding of how warfarin affects the coagulation cascade and describe the three common methods of reversal used for urgent surgery, namely Vitamin K, Fresh Frozen Plasma and Prothrombin Complex Concentrates (PCC). Although not required to pass, better answers included a description of warfarin’s mechanism and duration of action as it assisted in framing the remainder of the question. Marks were awarded for additional detail such as the advantages and disadvantages of IV / PO and low / high dose Vitamin K, composition of PCC and off-label use of recombinant Factor VIIa. Common mistakes included the belief that PCC are a recombinant product, role of cryoprecipitate and failing to discuss one or more of the three main reversal agents.
Model Answer
| Strategy | Considerations |
|---|---|
| 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 |
| 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 |
| FFP | - Contains all clotting factors - IV 15-30mL.kg-1 (or 2-4mL.kg-1 if with prothrombinex) - Pro: immediate - Con: 15-30mL.kg-1 = risk of TACO, risks of allogeneic transfusion |
| Prothrombinex | - Contains factors 2, 9, 10 (in Australia) - IV 25-50 units/kg - Pro: Immediate, universally compatible - Con: Factor 7 absent in Australian PCC |
| FEIBA | - Contains active factor 7a, inactive factors 2,9,10 - IV 50-100 units/kg - Pro: Contains all deficient coag factors - Con: Less data for warfarin reversal |
| Novoseven | - Activated Factor 7a - IV 50mcg.kg-1 - 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 |