1. April 23, 2015 Mini-Lecture Nathan King M.D. Anticoagulation Reversal Part 1: Warfarin

2. Objectives

3. A 73 year old male is admitted from the ED for failure to thrive. He has a history of CVA, CHF, and A.Fib on Coumadin. He has been living by himself in an apartment and only has the strength to prepare himself one meal a day. He has been admitted for placement. His INR on admission was 6.1. What is the most appropriate treatment strategy? A.Hold Coumadin, give 2.5mg PO Vitamin K1, then resume Coumadin at new dose of 2.5mg daily B.Hold Coumadin, give 5mg PO Vitamin K1, then resume Coumadin at home dose of 5mg daily C.Hold Coumadin until INR is <3 then resume at home dose of 5mg daily D.Hold Coumadin until INR is <2 then resume at home dose of 5mg daily Case Vignette

4. Mechanism of Warfarin and Reversal agents Warfarin Inhibits VKOR enzyme Decrease in activated Factors: II, VII, IX, & X Elevates PT/INR & PTT Reversed with Vit K, FFP, PCC, and rVIIa

5. Indications for anticoagulation reversal Supportive Measures / Monitoring: Support renal function with IVF and avoid nephrotoxins Monitor CBC and coags at lease Q12 hours Clinical Assessment: anticoagulation exposure possible medication interactions laboratory assessment: CBC, renal function, LFTs, and DIC screen

6. Warfarin Reversal Vitamin K1 IV formulation faster acting PO formulation results in less warfarin resistance SC changes INR equivalent to placebo – Poor bioavailability (DO NOT USE) Warfarin ½ life longer than hemostatic agents, definitive treatment must always include Vitamin K1 Hemostatic agents (PCC and rVIIa): Indicated for immediate reversal May instigate a thrombotic event Expensive Dezee KJ, Shimeall WT, Douglas KM, Shumway NM, O'malley PG. Treatment of excessive anticoagulation with phytonadione (vitamin K): a meta-analysis. Arch Intern Med. 2006;166(4):391.

7. Warfarin Reversal Adapted from: Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines (8th Edition). Chest 2008; (6 Suppl):160s And: UCI Guideline for acute management of bleeding in adults on warfarin, MH Tran et.al.

8. Adapted from: Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines (8th Edition). Chest 2008; (6 Suppl):160s Warfarin Reversal Non-bleeding patients that should be considered for Vitamin K treatment Age >70 Higher index INR Lower maintenance dose of warfarin Active cancer or heart failure

9. A 73 year old male is admitted from the ED for failure to thrive. He has a history of CVA, CHF, and A.Fib on Coumadin. He has been living by himself in an apartment and only has the strength to prepare himself one meal a day. He has been admitted for placement. His INR on admission was 6.1. What is the most appropriate treatment strategy? A.Hold Coumadin, give 2.5mg PO Vitamin K1, then resume Coumadin at new dose of 2.5mg daily B.Hold Coumadin, give 5mg PO Vitamin K1, then resume Coumadin at home dose of 5mg daily C.Hold Coumadin until INR is <3 then resume at home dose of 5mg daily D.Hold Coumadin until INR is <2 then resume at home dose of 5mg daily Case Vignette

10. A 73 year old male is admitted from the ED for failure to thrive. He has a history of CVA, CHF, and A.Fib on Coumadin. He has been living by himself in an apartment and only has the strength to prepare himself one meal a day. He has been admitted for placement. His INR on admission was 6.1. What is the most appropriate treatment strategy? A.Hold Coumadin, give 2.5mg PO Vitamin K1, then resume Coumadin at new dose of 2.5mg daily B.Hold Coumadin, give 5mg PO Vitamin K1, then resume Coumadin at home dose of 5mg daily C.Hold Coumadin until INR is <3 then resume at home dose of 5mg daily D.Hold Coumadin until INR is <2 then resume at home dose of 5mg daily Case Vignette

11. Summary IF Suspected of bleeding or bleeding risk on Warfarin: Determine if emergent reversal needed: ICH, emergent surgery, and major bleeding Initiate Supportive Measures and Clinical Assessment Warfarin Reversal: Vitamin K1 is essential DO NOT give SC Vitamin PCC or rVIIa for immediate reversal may have thrombotic complications Non-bleeding with High INR should be considered for Vitamin K1 if: >70 years, High initial INR, Low home dose, cancer or heart failure