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

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?

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

Evidence for Use of PCC

Evidence continued

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

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)

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

Rapid Reversal of Warfarin Order-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

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

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

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)

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

Case Study Continuted Head CT shows ICH Next Steps?

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

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