Management of Trauma Hemorrhage: Possible Role of Kcentra, a 4-factor Prothrombin Complex Concentrate Joli Dace, PharmD, BCPS Mercy Hospital and Trauma Center Saving Lives By Strengthening Our Region’s Trauma Care System Objectives Define PCC Differentiate PCCs available in US Identify action in coagulation cascade Compare Kcentra with FFP Review use of Kcentra in trauma: Emergent reversal of oral anticoagulants Management of trauma hemorrhage Discuss Kcentra nursing considerations What are PCCs? Prothrombin complex concentrates Concentrated clotting factors derived from pooled human plasma PCC Products Available in US Therapeutic Clotting Factors Profilnine SD® II, IX, X 3f-PCC Kcentra® II, IX, X, VII 4f-PCC BeriPlex® P/N (outside US) Activated 4f-PCC Feiba® NF II, IX, X, aVII Alternative Names Factor VIII Inhibitor Bypassing Activity Coagulation Cascade Tanaka KA, Key NS, Levy JH. Blood Coagulation: Hemostatis and Thrombin Regulation. Anesth Analg. 2009;108:1433-46. Comparison: Kcentra and FFP Kcentra® 3-6,18 FFP Clotting Factors II, VII, IX, X II, V, VII – XIII; fibrinogen Anticoagulants AT, heparin, protein C & S protein C & S Preparation Dilute each vial with 20mL Thaw; ABO match Volume Average 40 -100 mL/dose Average 30 mL/kg •Weight-based (~8-20min) Administration Rate •7x faster than FFP 3 Less volume and faster administration = faster Considerations restoration of factor levels3 Each unit over 30-60 min Dilutional coagulopathy Risk of transfusion-related acute lung injury Emergent Warfarin 2,3,4,7 Reversal Acute major bleed (head, spine, uncontrolled GI, extremity with risk of compartment syndrome) or Urgent surgery or invasive procedure within 6h2 INR Reversal ≤ 1.5 vitamin K 5 - 10 mg IV STAT 1.6 – 1.9 vitamin K + FFP 2.0 – 3.9 vitamin K + Kcentra 25 un/kg (max 2500 un) 4.0 – 6.0 vitamin K + Kcentra 35 un/kg (max 3500 un) > 6.0 vitamin see K + Kcentra For non-emergent warfarin reversal, 2012 50 un/kg (max 5000 un) Chest Guideline vitamin K recommendations7. Emergent NOAC (Novel Oral Anticoagulants)Reversal Strategies8-12 NOAC Drug Class Factor Xa Inhibitors NOAC Agents apixaban (Eliquis) rivaroxaban (Xarelto) Direct Thrombin (IIa) Inhibitor dabigatran (Pradaxa) Coagulation Tests anti-Xa, PT, aPTT ECT, dilute TT, aPTT Activated Charcoal? Yes, if last dose < 2h ago. Yes, if last dose < 2h ago. Hemodialysis? Not useful. Yes – prolonged (2h+) PCC to reverse? Kcentra 25 – 50 un/kg Kcentra 25 – 50 un/kg Alternative Reversals? ? FEIBA 25 un/kg10 aDabi-Fab (future)11 Management of Trauma Hemorrhage – Standards of Care16 Consider TXA early (bleeding or at risk) Correct hypothermia, acidosis, hypotension Maintain Hgb (7-9 g/dL), plts (50-100k) Fibrinogen – maintain > 1.5 – 2 mg/dL19 Depleted earlier than blood factors Risk factors for low fibrinogen level on admission14: at 142% blood loss vs. 200-240% before fII, fVII critically low13 injury severity score, shock, SBP<90, prehospital fluid volume Calcium – maintain iCa > 0.920 PCC in Trauma Hemorrhage Evidence-supported benefit? Thrombosis risk: low (0-1.4% for current 4fPCCs) Lack of prospective trials demonstrating mortality benefit Retrospective reports demonstrate decreased INR, bleeding, need for PRBCs, stabilized blood pressure22-25 Guidelines differ16,17; local use positive Exclusion criteria: DIC, HIT optimal Kcentra dose: unclear. (?25-50 un/kg; max 100kg) Possibly consider Kcentra for: Massive hemorrhage unresponsive to conventional tx TEG-guided: ongoing bleed with CT > 90s15 Hgb-driven “Coagulation Box” model: Hgb < 5.526 Kcentra – Nursing Considerations Verbal orders Clarify which “PCC”, what un/kg dose (fIX), indication Contact blood bank or pharmacy to alert of STAT order Administration Concentration, dose and rate vary (~10-20 min) Emergent reversal. Give ASAP (expires 4hrs after mixed) Document lot numbers (blood product) Monitor for allergic reactions and thrombosis (0.9-1.4%) Cost References 1. Tanaka KA, Key NS, Levy JH. Blood Coagulation: Hemostatis and Thrombin Regulation. Anesth Analg. 2009;108:1433-46. 2. National Advisory Committee on Blood and Blood Products. Recommendations for use of prothrombin complex concentrates in Canada. Accessed on 11/7/2014. http://www.nacblood.ca/guidelines/PCC-Recommendations-Final-2014-05-16.pdf. 3. Kcentra website: www.Kcentra.com. Maintained by CSL Behring. 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