<p> 500-56, Attachment C Anticoagulant & Antiplatelet Reversal/Rescue Guidelines, revised 11/2015 The recommendations below are guidelines and require a licensed independent practitioner order.</p><p>Section I: Coumadin (warfarin) Reversal Guidelines Section II: Oral Anticoagulant Reversal Guidelines Section III: IV/SQ Anticoagulant Reversal Guidelines Section IV: Antiplatelet & Fibrinolytic Reversal Guidelines Section I: Coumadin (warfarin) Reversal Guidelines Clinical Pharmacist may change Vitamin K IV, IM or SQ to oral if the patient can tolerate oral medications using these guidelines below. Orders will be signed “Per Policy” (See Route Change Policy 7300-VII-50)</p><p>INR Symptoms Recommendations: 2-3.5 Surgery/Procedure:  Stop warfarin 4-5 days prior to surgery and begin heparin or  Scheduled LMWH as indicated by disease state.  Stop warfarin, and give Vitamin K 2.5- 5 mg po. May repeat  Urgent (24-48hrs) Vitamin K 1-2mg orally if INR is still elevated.</p><p> Emergency (< 24 hrs)  Reverse warfarin with Vitamin K 2.5-5 mg IV or orally. For more immediate reversal, give FFP plus Vitamin K 2.5-5 mg IV or orally.  MAX Vit K 10 mg IV x 1 dose. If INR still elevated after 12 hrs, may repeat Vit K 10 mg IV dose. 3.5 to <5  No bleeding  Omit next dose and/or resume at a lower dose when the INR is at therapeutic level > 5 - 9  No significant bleeding  Omit next 1-2 doses and resume at lower doses when INR in therapeutic range OR  Omit dose and give Vitamin K 1 – 2.5mg orally if patient is at increased risk of bleeding.</p><p>> 9  No significant bleeding  Hold warfarin, give Vitamin K 2.5 – 5 mg orally.  Resume at lower doses when INR in therapeutic range. At any  Serious bleeding or  Hold warfarin therapy and give Vitamin K 10mg slow IV elevation of major warfarin infusion (may repeat in 12 hours for persistent INR elevation) and INR overdose FFP (or prothrombin complex concentrate depending on the urgency of the situation. Factor VIIa may be considered as an alternative to prothrombin complex concentrate) At any  Life-threatening  Hold warfarin therapy elevation of bleeding  Vitamin K 10 mg IV in 50 ml NS over 30 minutes PLUS INR  Prothrombin Complex Concentrate (Kcentra, 4-Factor, seq # 35127) </p><p>May repeat vitamin K 5-10mg INR < 2 – 4: 25 units/kg (max dose 2,500 units) IVPB at < 8ml/min. IVPB q12hrs until INR < 1.4 INR 4 – 6: 35 units/kg (max dose 3,500 units) IVPB at < 8ml/min. (PO time to effect = 24 hrs) I NR > 6: 50 units/kg (max dose 5,000 units) IVPB at < 8ml/min. (IV time to effect = 12 hrs) ***Recheck INR 30 Min after infusion completed. If bleeding continues, consider cryoprecipitate for fibrinogen < 100mg/ml, FFP, or platelet transfusion. *** OR Vitamin K 10 mg IV in 50 ml NS over 30 minutes. + </p><p>Page 1 of 6 500-56, Attachment C NovoSeven (FVIIa) 15-30 mcg/kg x 1 (half-life ~ 2 hours) + FFP Section II: Oral Anticoagulant Reversal Guidelines The recommendations below are guidelines and require a licensed independent practitioner order. </p><p>Drug Reversal Agent Interventions for Severe or Lab Life-threatening Bleeding Eliquis None PT lab value is not (apixaban) Charcoal < 6 hours ingestion of clinical utility in measuring adequate The following may be of value but anti-coagulation but NO/limited human evidence has qualitative value for situations such Prothrombin Complex Concentrate as in severe (Kcentra, 4-Factor, seq # 35127) overdose or 50 units/kg IVPB (max dose 5,000 units) at evaluation of 0.12 ml/kg/min (max 8 ml/min). compliance. Effect should be seen in < 30 minutes OR NovoSeven (Factor VIIa) 2 mg < 100 kg, 4 mg > 10 0 kg IV bolus over 3-5 minutes. Effect should be seen in < 30 minutes. May repeat in 2 hours if bleeding con tinues. Pradaxa Praxbind (idarucizumab) aPTT (dabigatran) 5 gm Charcoal if < 2 hr of ingestion (normal value (2 vials, each contains suggests little or Class: 2.5 gm/50 ml) The following may be of value but no anticoagulant Direct Thrombin IVP over 5 minutes NO/limited human evidence: activity) (max of Inhibitor May repeat dose after 12-24 hrs only Factor VIIa 2 mg if < 100 kg, 4 mg if > 100 kg IV 2X control) if the following 2 criteria are met: push over 3-5 minutes x 1, may repeat in 2 hrs if or PTT is elevated bleeding continues. TT (too sensitive AND OR but of qualitative patient is still experiencing life- Prothrombin Complex Concentrate threatening bleeding value, normal (Kcentra, 4-Factor, seq # 35127) value suggests 50 unit/kg IVPB (max dose 5,000 units) at little or no 0.12 ml/kg/min (max 8 ml/min) anticoagulant activity) Anticoagulant effect is through direct clotting factor inhibition and not clotting factor depletion, therefore ECT is a sensitive FFP/PCC/Factor VII is not anticipated to be wholly measure with direct effective in reversing. linear correlation but Protamine and Vit K have no effect. not commercially available. Give platelets if thrombocytopenia present or if long acting antiplatelets drug have also been used.</p><p>Xarelto None PT lab value is not (Rivaroxaban) Charcoal < 2 hours ingestion of clinical utility in measuring adequate Class: The following may be of value but anti-coagulation but NO/limited human evidence has qualitative value Xa Inhibitor for situations such Prothrombin Complex Concentrate as in severe (Kcentra, 4-Factor, seq # 35127) overdose or 50 units/kg IVPB (max dose 5,000 units) at evaluation of 0.12 ml/kg/min (max 8 ml/min). compliance. Effect should be seen in < 30 minutes OR Factor VIIa 2 mg < 100 kg, 4 mg > 100 kg IV bolus over 3-5 minutes. Effect should be seen in < 30 minutes. May repeat in 2 hours if bleeding continues.</p><p>Page 2 of 6 500-56, Attachment C</p><p>Section III: IV/SQ Anticoagulant Reversal Guidelines The recommendations below are guidelines and require a licensed independent practitioner order. Drug Reversal Agent Interventions for Severe or Lab/Comments Life-threatening Bleeding Angiomax None Discontinue infusion. Monitor ACT (bivalirudin) Anticoagulation parameters generally return to Short half-life and baseline quickly at 1 hr discontinuation are primary means of Class: attenuating bleed – Direct Thrombin Fibrinogen in the form of FFP or cryoprecipitate can support with Inhibitor be given to work as a competitor to displace crystalloid and blood bivalirudin from thrombin. products to facilitate rapid renal clearance. Amicar (aminocaproic acid) 5 gm in 250 ml NS IV over 1 hour then 5 gm/250ml NS at 50 ml/hr infusion can be used until bleeding ceases</p><p>Argatroban None Discontinue infusion Monitor PTT. Anticoagulation parameters generally return to Short half-life and Class: baseline quickly at 2-4 hrs. discontinuation are primary means of Direct Thrombin attenuating bleed – Inhibitor Factor VIIa 2 mg < 100 kg, 4 mg > 100 kg IV bolus support with over 3-5 minutes. Effect should be seen in < 30 crystalloid and blood minutes. May repeat in 2 hours if bleeding continues. products to facilitate Limited human evidence. rapid renal clearance. May be of value but use as last resort.</p><p>Arixtra None Administration of rVIIa and PCCs has been shown to (fondaparinux) reverse the anticoagulation effects of fondaparinux in small studies and may be considered as an option. Class: Xa Inhibitor Factor VIIa 2 mg < 100 kg, 4 mg > 100 kg IV bolus over 3-5 minutes. Effect should be seen in < 30 minutes. May repeat in 2 hours if bleeding continues. </p><p>OR</p><p>Prothrombin Complex Concentrate (Kcentra, 4-Factor, seq # 35127) 50 units/kg IVPB infused at 0.12ml/kg/min (max 8 ml/min). Effects should be seen in < 30 minutes.</p><p>Page 3 of 6 500-56, Attachment C</p><p>Drug Reversal Agent Interventions for Severe or Lab/Comments Life-threatening Bleeding Heparin Protamine (max dose 50 mg) Protamine IV administration: Recheck Heparin IV bolus: Slow IV push at 5mg/min with anti-Xa Heparin  < 30 min: Protamine 1-1.5 max of 50 mg per dose. level 15 minutes mg per 100 units heparin post dose to assess administered response.  30-60 min: Protamine 0.5- 0.75 mg per 100 units heparin administered  1-2 hrs: Protamine 0.375- 0.5 mg per 100 units heparin administered  2 hrs: Protamine 0.25-0.375 mg per 100 units heparin administered Heparin Infusion:  Protamine 1 mg per 100 units heparin administered over last 4 hours Heparin SQ:  Protamine 1-1.5 mg per 100 units heparin administered LMWH Protamine (partial reversal) Anti-Xa level Low Molecular max dose 50 mg Protamine IV administration: Weight Heparin: Within 8 hrs of last dose: Slow IV push at 5mg/min with Protamine 1 mg per 1mg max of 50 mg per dose. Lovenox LMWH. May repeat 2-4 hrs (enoxaparin) prn with Protamine 0.5 mg per 1mg LMWH Fragmin 8-12 hrs of last dose: (dalteparin) Protamine 0.5 mg per 1 mg LMWH > 12 hrs of last dose: None</p><p>Page 4 of 6 500-56, Attachment C Section IV: Antiplatelet & Fibrinolytic Reversal Guidelines The recommendations below are guidelines and require a licensed independent practitioner order. </p><p>Drug Reversal Agent Interventions for Severe or Lab/Comments Life-threatening Bleeding Activase/TNK None Cryoprecipitate 8-12 units + Fibrinogen (alteplase/ FFP (fresh frozen plasma) 2 units + tenecteplase) Protamine (if heparin administration)</p><p>Class: If bleeding continues consider: Fibrinolytic Platelet infusion Amicar (aminocaproic acid) 5 gm in 250 ml NS IV over 1 hour then 5 gm/250ml NS at 50 ml/hr infusion until bleeding ceases Aspirin None Platelet transfusion Salicylate level or Class: May consider DDAVP (desmopressin) 0.3 mcg/kg Platelet inhibition Cox 1 and 2 administered over 15 min to augment platelet function test inhibitor in addition to platelet transfusion. (serial doses associated with tachyphylaxis, hyponatremia, and seizures) </p><p>Brilinta None No data exist with BRILINTA regarding a Plavix Inhibition (ticagrelor) hemostatic benefit of platelet transfusions. test Brilinta is a reversible inhibitor and platelet (goal platelet Class: function normalizes after drug clearance. Circulating function inhibition Reversible ADP- Brilinta may inhibit transfused platelets. < 20%) receptor antagonist Amicar (aminocaproic acid) 100 mg/kg IV (max 5 gm dose) over 30-60 min, then maintenance oral or IV: 1-4 gm q 4-8 hrs or 1 gm/hr until hemostasis achieved with max daily dose 24 gm or FVIIa 15-30 mcg/kg IV push over 3-5 minutes x 1, may repeat in 2 hours if bleeding continues or May consider DDAVP (desmopressin) 0.3 mcg/kg administered over 15 min to augment platelet function May be ineffective if Plavix inhibition test (Verify Now) is < 20% (serial doses associated with tachyphylaxis, hyponatremia, and seizures) </p><p>Effient None Platelet transfusion Plavix Inhibition (prasugrel) (may require 2-3 plateletpheresis to reverse Effient Test induced platelet disaggregation) (goal platelet function inhibition May consider DDAVP (desmopressin) 0.3 mcg/kg < 20%) administered over 15 min to augment platelet function in addition to platelet transfuion. May be ineffective if Plavix inhibition test (Verify Now) is < 20% (serial doses associated with tachyphylaxis, hyponatremia, and seizures) </p><p>Page 5 of 6 500-56, Attachment C</p><p>Drug Reversal Agent Interventions for Severe or Lab/Comments Life-threatening Bleeding Aggrastat None Discontinue infusion None (tirofiban) (Normal platelet function resumes 4-6 hrs after holding Aggrestat) Short half-life and Platelet transfusion only with thrombocytopenia discontinuation are primary means of Class: attenuating bleed – GP-IIaIIIb support with Inhibitor May consider DDAVP (desmopressin) 0.3 mcg/kg crystalloid and blood administered over 15 min to augment platelet function products to facilitate rapid renal clearance (serial doses associated with tachyphylaxis, hyponatremia, and seizures) Plavix None Platelet transfusion Plavix Inhibition (clopidogrel) (may require 2-3 plateletpheresis to reverse Plavix test Class: induced platelet disaggregation) (goal platelet ADP-receptor function inhibition antagonist May consider DDAVP (desmopressin) 0.3 mcg/kg < 20%) administered over 15 min to augment platelet function in addition to platelet transfusion. May be ineffective if Plavix inhibition test (Verify Now) is < 20% (serial doses associated with tachyphylaxis, hyponatremia, and seizures) </p><p>OR </p><p>FVIIa 10-20 mcg/kg IV push over 3-5 min x 1, may repeat in 2 hours if bleeding continues Ticlid None Platelet transfusion Plavix Inhibition (ticlopidine) test Class: (goal platelet ADP-receptor May consider DDAVP (desmopressin) 0.3 mcg/kg function inhibition antagonist administered over 15 min to augment platelet function < 20%) in addition to platelet transfusion. May be ineffective if Plavix inhibition test (Verify Now) is < 20% (serial doses associated with tachyphylaxis, hyponatremia, and seizures) </p><p>Page 6 of 6</p>