LAMC Reversal Agent Guideline for Anticoagulants 2013 Medication resolution of hemostasis (hrs) Intervention Administration Instructions Heparin 3-4 Protamine 1mg IV for every 100 units of heparin Slow IV push NTE 5mg/min or 50mg total dose Enoxaparin (Lovenox) 12-36 Protamine partially reverses the anticoagulant effect of LMWHs (60%) Hrs prior to last Dose dose administration Warfarin 60-80 VITAMIN K: INR Clinical Setting <8 hours 1mg protamine per 1mg enoxaparin 8-12 hours 0.5mg protamine per 1mg enoxaparin >12 hours Protamine unlikely to be beneficial Therapeutic Options <4.5 No bleeding Hold warfarin until INR in therapeutic range Rapid reversal required Hold warfarin Consider vitamin K 2.5mg PO 4.5-10 No bleeding Hold warfarin until INR therapeutic range Consider vitamin K 2.5-5mg po Rapid reversal required Hold warfarin Give vitamin K 2.5-5mg po >10 No bleeding Hold warfarin until INR in therapeutic range Give vitamin K 2.5-5mg PO Rapid reversal required Hold warfarin Give vitamin K 2mg IV infusion Any INR Serious or Life Threatening bleeding Hold warfarin Give vitamin K 10mg IV infusion over 30 min. Give 2 units FFP Give PCC (Kcentra) See dosing below Slow IV push NTE 5mg/min or 50mg total dose Vitamin K IV: NTE 1mg/min; a 15-30 minute infusion Note: Vitamin K should not be administered to patients with prosthetic heart valves, only low doses (1mg) should be used if absolutely necessary effect (Hours) Lab Testing <0.25 aptt <0.25 Anti-Xa PO: 24-48 IV: <24 INR
Medication resolution of hemostasis (hrs) Intervention Warfarin 60-80 KCENTRA: Administer with Vitamin K Bleeding Event: Pre-treat INR 2 to <4 25 units/kg NTE 2500 units 4-6 35 units/kg NTE 3500 units >6 50 units/kg NTE 5000 units Dose Administration Instructions Kcentra: Administer at room temperature by IV infusion (0.12ml/kg/min (~ 3units/kg/min) up to a maximum rate of 8.4ml/min) effect (Hours) Lab Testing INR FACTOR Xa Inhibitors: Rivaroxaban (Xarelto) Apixaban (Eliquis) Normal renal 12-24 36-48 hours for renally impaired Activated Charcoal with Sorbitol 1g/kg (max 50g)x1 dose 2 units FFP (recheck INR 1 hour after administration of FFP) Profilnine SD 25-50 units/kg x1 Kcentra 25-50 units/kg x1 Within 2 hours of ingestion Maximum rate 10ml/min IV infusion (0.12ml/kg/min (~ 3units/kg/min) up to a maximum rate of 8.4ml/min Anti-Xa aptt,pt rfviia (Novoseven) 45-90 mcg/kg IV x1 IV bolus over 2-3 minutes Fondaparinux (Arixtra) Monitor PT/INR and anti-factor Xa assay to confirm reversal Fondaparinux: All the above options except for activated charcoal with sorbitol Monitor aptt to confirm reversal Anti-Xa
Medication Direct Thrombin Inhibitors (DTIs) Argatroban Bivalirudin (Angiomax) resolution of hemostasis (hrs) 2-4 1-2 Intervention Turn off the infusion FFP 2 units (recheck INR 1 hour after administration of FFP) Profilnine SD 25-50 units/kg x1 Kcentra 25-50 units/kg x1 Administration Instructions Maximum rate 10ml/min IV infusion (0.12ml/kg/min (~ 3units/kg/min) up to a maximum rate of 8.4ml/min effect (Hours) Lab Testing aptt Dabigatran (Pradaxa) t1/2=12-17; 15-34 renal impairment rfviia (NovoSeven) 45-90 mcg/kg/ivx1 Dialysis: Removes ~ 60% dabigatran Activated Charcoal with Sorbitol 1gm/kg (Max 50gm) PO x1 dose FFP 2units (recheck INR 1 hour after administration of FFP) Profilnine SD 25-50 units/kg x1 Kcentra 25-50 units/kg X1 IV bolus over 2-3 minutes Ingested within 2 hours Maximum rate 10ml/min IV infusion (0.12ml/kg/min (~ 3units/kg/min) up to a maximum rate of 8.4ml/min ECT (Ecarin Clotting Testing) TT aptt rfviia (NovoSeven) 45-90 mcg/kg/ivx1 (no data about additional benefit (only animal evidence) IV bolus over 2-3 minutes ANTIPLATELETS: Clopidogrel (Plavix) Prasugrel (Effient) Ticagrelor (Brilinta) T1/2=8 hrs T1/2 = 7 hrs T1/2= 7 hrs 1 unit apheresis platelets DDAVP 0.3mcg/kg Variable Dilute in 50ml saline and infuse over 15 minutes <0.25 <0.25 Platelet Function assays
Los Alamitos Medical Center Pharmacy Department Policy and Procedure Title/Subject: ADULT Anticoagulant Reversal Guidelines Section: 13 Number: RXM-13.38 ORIGINAL DATE: 10/13 REVIEW DATE: 10/13 REVISED DATE: Page 1 of 3 I. Scope: Pharmacy Department This is a Los Alamitos Medical Center Policy and Procedure. II. Purpose: To improve therapeutic outcomes for patients experiencing bleeding events while receiving anticoagulants at Los Alamitos Medical center. Although many older anticoagulants have clearly established antidotes (ie. Warfarin, heparin) newer agents which are demonstrating increased effectiveness for a variety of disorders have no real reversal strategies available. These guidelines, to be updated yearly, will review the most current literature to support health care providers in their attempt to safely stop bleeding for patients with complications on anticoagulants. III. Policy: Any new bleed, major or minor, for a patient receiving anticoagulants will be reported to the treating physician. At the treating physician s recommendation, the following strategies may be used to handle bleeding events: Holding the anticoagulant Using a pharmacologic antidote Using a physical antidote (ie. Dialysis) Administration of blood products Any combination of the above IV. Procedure: A. Baseline bleed risk assessment will be performed on all patients receiving anticoagulants. In addition, baseline and periodic labs will be drawn including but not limited to: CBC, Scr, PT/INR, and aptt. B. Nursing will perform daily assessments for signs of bleeding in all patients treated with anticoagulants. These may include signs/symptoms of any of the following: melana, bruising, epistaxis, gingival hemorrhage, or hematoma formation.
Los Alamitos Medical Center Pharmacy Department Policy and Procedure ORIGINAL DATE: 10/13 REVIEW DATE: 10/13 REVISED DATE: Page 2 of 3 Title/Subject: ADULT Anticoagulant Reversal Guidelines Section: 13 Number: RXM-13.38 C. Note: There is no specific reversal agent or pharmacologic antidote for direct thrombin inhibitors,dabigatran, Xa inhibitors, and anti-platelet agents. Patient on anticoagulation may be treated using the reversal guideline. D. For moderate bleeding events, consider the following: Symptomatic treatment Mechanical compression Surgical intervention Fluid replacement and hemodynamic support Blood product transfusion E. For severe or life threatening bleeding events, a hematology consult should be considered for further recommendations. REVERSAL AGENTS: 1. Protamine Treatment of choice for both heparin and enoxaparin reversal Heparin protamine dosed based on the time since heparin has been stopped Enoxaparin- reversal will only neutralize approximately 60^ of the anti-xa activity; repeat dose may be given in 2-4 hours if the aptt has not returned to normal. Pre-medicate with corticosteroids and antihistamines if a risk for protamine allergy (caution with patients with a fish allergy): 1. Hydrocortisone 50-100mg IV x1 over 15 minutes 2. Diphenhydramine 50mg IV/PO x1 2. Vitamin K: Treatment of choice for reversal from warfarin activity Oral Vitamin K is preferred Vitamin K IV to be given when INR>10 and /or when the patient is actively hemorrhaging. In addition, keep the doses of vitamin K as low as possible to prevent difficulty in getting the patient back to therapeutic range once the event has resolved (per 2012 CHEST guidelines for Antithrombotic Therapy and Prevention of Thrombosis).
Los Alamitos Medical Center Pharmacy Department Policy and Procedure ORIGINAL DATE: 10/13 REVIEW DATE: 10/13 REVISED DATE: Page 3 of 3 Title/Subject: ADULT Anticoagulant Reversal Guidelines Section: 13 Number: RXM-13.38 3. Prothrombin Concentrate Complex: Potential efficacy in the reversal of direct thrombin inhibitors and anti-factor Xa agents (per 2012 CHEST guidelines for Antithrombotic Therapy and Prevention of Thrombosis) Kcentra agent of choice in combination with vitamin K for URGENT warfarin rescue 4.Activated charcoal: To aid in reversal of the following oral anticoagulants: rivaroxaban, apixaban, and dabigatran if ingested within 2 hours. Mix with flavoring agents to enhance compliance 5.DDAVP: Reversal of bleeding associated with antiplatelet agents May have a role in the rescue of GPIIB/IIIA inhibitors Extremely short half-life
References: 1. Davis, Jonathan E. Reversing Medications that Cause Bleeding. Presentation at the ACEP Scientific Assembly. Las Vegas. 9/28/2012. 2. Dumkow, Lisa E et al. Reversal of Dabigatran-Induced Bleeding with a Prothrombin Complex Concentrate and Fresh Frozen Plasma. Am J Health-Syst Pharm vol 69. 10/1/2012. 3. Ghanny, Shari et al. Reversing Anticoagulant Therapy. Current Drug Discovery Technologies. 9, 143-149. 2012. 4. Levi, Marcel. Emergency Reversal of Antithrombotic Treatment. Intern Emerg Med.4:137-145.2009. 5. Miyares, Marta A et al. Newer Oral Anticoagulants: A Review of Laboratory Monitoring Options and Reversal Agents in the Hemorrhagic Patient AM J Health-Syst Pharm. Vol 69.2012. 6. Nagle, Erin L et al. Bivalirudin for Anticoaulation During Hypothermic Cardiopulmonary Bypass and Recombinant Factor VIIa for latrogenic Coagulopathy. The Annals of Pharmacotherapy.vol 45.9/2011. 7. www.med.unc.edu/../files/emergent-anticoagulation-reversal-in-the-ed Feb 2013 8. Nitzki-George, Diane. Current State of Knowledge on Oral Anticoagulant Reversal Using Procoagulant Factors. The Annals of Pharmacotherapy.vol 47.6/2013. 9. Europace(2013) 15.625-651. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation.