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: Kcentra Replaces: factor II, VII, IX and X (vit K dependent coag. Factors) Works by temporarily raising the levels of these clotting factors AHA / ASA class IIb recommendation

PCC: Risk factors Allergic reaction DIC Thrombosis Chills, headache, fever, nausea and vomiting, rash, anaphylactic reaction If this occurs, stop infusion and treat with antihistamines DIC Thrombosis

Rapid Reversal of Warfarin Order-set Restricted to the ED, Critical Care, and OR Indications: 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 Notify blood back and core lab Alert: Neurosurgical Emergency, Name, and MR # STAT PT/INR, PTT, D-dimer, fibrinogen, CBC, in a bag labeled STAT to hematology STAT type and screen to blood bank STAT BMP and LFTs

Next Steps (per order-set) Administer Vitamin K 10 mg slow IV Administer PCC (Kcentra) INR < 5 500 IU of Kcentra IV INR > 5 1000 IU of Kcentra IV Rate: Do not exceed 5 ml per minute IV Push Administer Platelets if Plt < 100,000 DDAVP (Desmopressin) - consider if plt dysfunction present

Administration of PCC Available from the Blood Bank Needs to be reconstituted immediately prior to use Does not contain a preservative and must be used within 3 hours of reconstitution Do not refrigerate Concentrate should be drawn up with the contents in the package obtained from the blood bank Administer IV at a maximum rate of 5ml / min IVP

PCC IV Infusion How to prepare the medication Follow up Labs: You will receive a kit from the blood bank 2 minute administration video available at: www.kcentra.com Video listed under dosing and administration Note: The website indicates a weight based dosing with the INR. The dosing at MAH will only be based on INR. Follow up Labs: PT/INR 10 - 15 min after the infusion is complete

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?

Summary Coagulopathy puts patients at high risk for ICH Vitamin K FFP Effective, but slow onset FFP Effective, but slow and risk of volume overload PCC - is effective and fast acting Orderset is available now under “evidence and ordersets” on the portal Orderset title: “Kcentra Rapid Reversal Warfarin”

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