Rapid Reversal of Warfarin Therapy in Patients with Intracranial / Intraspinal Bleeding

1. Rapid Reversal of Warfarin Therapy in Patients with Intracranial / Intraspinal Bleeding Mount Auburn Hospital Blood Bank, Emergency Department, Critical Care, Neurosurgery, Hem-Onc, Quality and Safety

2. Clinical Questions • What are the treatment options for anticoagulation reversal? • How fast do they work? • What are the risk factors? • What is the Rapid Reversal of Warfarin Order-Set?

3. Background • Life threatening bleeds in patients on wafarin - Timely reversal is IMPERATIVE! • Current Treatment Options: • FFP • Concerns: Delayed treatment (thaw time), volume overload, inadequate correction • Vitamin K IV • Concerns: Length of onset time • Prothrombin Complex Concentrate (PCC) • Desmopressin (DDAVP) • Increases levels of VWF and factor VIII Now Available

4. Evidence for Use of PCC

5. Evidence continued

6. Main Points: • PCC normalizes INR faster than FFP • PCC is recommended for patients with life-threatening • warfarin related bleeding • PCC, vitamin K IV, and FFP should all be available for this • patient population

7. PCC: What is it? • Also called: Bebulin (the brand name) • Factor IX complex concentrate and has high levels of factor II, IX and X (vit K dependent coag. Factors) • Low level of factor VII • Works by temporarily raising the levels of these clotting factors • AHA / ASA class IIb recommendation • Cost: $1500 / dose ($1 / IU)

8. PCC: Adverse Reactions • Allergic reaction • Chills, headache, fever, nausea and vomiting, rash  tx with antihistamines • Anaphylactic reaction  tx immediately • Thrombosis (small risk factor)

9. Rapid Reversal of WarfarinOrder-set • Restricted to the ED, Critical Care, and OR • Indications: Confirmed CT with Intracranial or Intraspinal hemorrhage with elevated INR • Exclusions: HIT in previous 3 months • Relative contraindications: • DIC, history of recent thrombosis, MI, Ischemic Stroke

10. Initial Work-up • STAT head CT • Once Head CT confirmed: • Notify/ CALL blood bank and core lab • Blood bank x 5096 • Core Lab x 5060 • Neurosurgical Emergency: Patient Name, and MR # • All labs need to be handed to a lab tech • STAT PT/INR, PTT, D-dimer, fibrinogen, CBC, in a bag labeled STAT to core lab • STAT type and screen to blood bank • STAT BMP and LFTs

11. Next Steps (per order-set) 1) Immediately Administer Vitamin K 10 mg slow IV infusion 2) Administer PCC (Bebulin) • INR < 5 20ml Bebulin IV (~ 500 IU) • INR > 5 40ml Bebulin IV (~ 1000 IU) • Rate: Do not exceed 2 ml per minute IV 3) 2 units FFP given 4) Consider Plt if Plt < 100,000 5) Consider DDAVP (Desmopressin) - If plt dysfunction present

12. Post Initial PCC infusion • Follow up Labs: 10 - 15 min AFTER PCC infusion is complete: STAT PT / INR • Goal: Normalization of INR with in shortest time possible • Further management: Per attending MD • Additional labs may be needed per the pathologist or MD • Maximum I.U. per Medical Director of blood bank (~ 3000 IU maximum)

13. Case Study • 71 yo M with sudden onset of a severe headache and blurred vision • Vitals: BP 200/90, HR 92, RR 14, Temp 98 • PMH: Afib, CAD, HTN, diabetes • Medications: • Warfarin 5mg daily • Lopressor 25mg BID • Lipitor 20mg daily • Glucaphage 10mg BID

14. Case Study Continuted • Head CT shows ICH • Next Steps?

15. Conclusions • Coagulopathy puts patients at high risk for ICH • Vitamin K • Effective, but slow onset • FFP • Effective, but slow and risk of volume overload • PCC - is effective and fast acting • Order - set is available now • When given together Vit. K, FFP, and PCC can quickly normalize INR

19. References • Chest 2008; 133 (6Suppl): 160S - 198S • Stroke 2007; 38; 2001 - 2023 • Yasaka M et al; Optimal dose of PCC for acute reversal of oral anticoagulation. Thromb Res. 2005; 115; 455 - 459 • Nat’l Advisory Committee on Blood and Blood Products, September 2008