Emergent reversal
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Emergent reversal

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Emergent reversal Emergent reversal Presentation Transcript

  • David Barounis R-2Advocate Christ Medical Center
  • Some Questions to theAudience1. How much does FFP cost and how much do you need to give in reversal of coumadin associated life threatening bleed??
  • Some Questions to theAudience1. How much does FFP cost and how much do you need to give in reversal of coumadin associated life threatening bleed?? A: $1/ml, typically need 4U for reversal with 250cc/unit = $1000.1. What other products are available here at christ hospital for reversal of oral anticoagulants?
  • Case 11. 65y/o F with A-fib presents on Pradaxa presents with an ICH approximately 25cc volume with no significant shift. What’s you next move??
  • Case 2 58y/o M s/p total hip replacement on rivaroxaban for DVT prophylaxis presents with lightheadness and weakness. Hgb is 4.2 guaic negative from below. Where is the bleed?
  • Case 2 58y/o M s/p total hip replacement on rivaroxaban for DVT prophylaxis presents with lightheadness and weakness. Hgb is 4.2 guaic negative from below. Where is the bleed? CT A/P: Large retroperitoneal hematoma
  • Coagulation Cascade
  • Coagulation Cascade
  • The ER coagulationcascade Tissue Damage OTHER FACTORS V, VIII, IX, XI, XII 1.FACTOR VIIa 2.FACTOR Xa ==FACTOR X 3.PROTHROMBIN== THROMBIN FIBRONGEN ==FIBRIN CLOTS
  • The ER coagulationcascade COUMADIN Tissue Damage OTHER FACTORS V, VIII, IX, XI, XII 1.FACTOR VIIa 2.FACTOR Xa ==FACTOR X 3.PROTHROMBIN== THROMBIN FIBRONGEN ==FIBRIN CLOTS
  • The ER coagulationcascade Tissue Damage OTHER FACTORS V, VIII, IX, XI, XII LOVENOX 1.FACTOR VIIa AT III HEPARIN 2.FACTOR Xa ==FACTOR X 3.PROTHROMBIN== THROMBIN FIBRONGEN ==FIBRIN CLOTS
  • Dabigatran(Pradaxa) Direct Thrombin Inhibitor Approved for anti-coagulation in patients with non-valvular atrial fibrillation RE-LY trial comparing coumadin to Dabigatran
  • The ER coagulationcascade Tissue Damage OTHER FACTORS V, VIII, IX, XI, XII 1.FACTOR VIIa 2.FACTOR Xa ==FACTOR X 3.PROTHROMBIN== THROMBIN PRADAXA FIBRONGEN ==FIBRIN CLOTS
  • Back to Case 1 ICB in patient on pradaxa Step 1: What is the patients aPTT?The PTT, typically 1.5X normal 12hoursafter last dose. If < 32 seconds unlikely forpatient to have high enough bloodconcentrations for benefit from reversal
  • Novel Reversal Agents1. PCCWE DO NOT HAVE PCC’s here at ChristHospital.Cost is similar to 4U of FFP($1000 vs $1200)USA 3 factor PCC’s only (does not contain high quantityof factor VII)So assuming 4U (1L) of FFP vs 2000U of ProfilnineFactor II: 1000U FFP : 2900U ProfilnineFactor IX: 1000U FFP : 2000U ProfilnineFactor VII: 1000U FFP: 700U ProfilnineFactor X: 1000U FFP : 1200U Profilnine
  • PCC’s Safety*1.4% complication rate (3 CVA, 2 DVT, and 2 non Q wave MI’s)
  • The ER coagulationcascade Tissue Damage OTHER FACTORS V, VIII, IX, XI, XII 1.FACTOR VIIa PCC’s 2.FACTOR Xa ==FACTOR X 3.PROTHROMBIN== THROMBIN PRADAXA FIBRONGEN ==FIBRIN CLOTS
  • Are they effective in patientswith non-VKA?Reversal of Rivaroxaban and Dabigatran by ProthrombinComplex Concentrate. Circulation 201112 healthy volunteers: No effect of PCC on Dabigatranreversal, completely reversed measured anticoagulation insubjects receiving Rivaroxaban.JUST REMEMBER THIS IS IN HEALTHY PT VOLUNTEERSWITHOUT HEAD BLEEDS!!!
  • Activated Factor VIIa(Novo7) Recommended by the makers of Dabigatran as the “Reversal agent of choice”. Dose 90mcg/kg = 1mg Very short half life and often requires repeated dosing ($1.13/mcg, usually need 1mg X 4 INITIAL X 4 MAINTENCE OVER 4-6 HOURS= $55,000)
  • Safety of Novo7 Thromboembolic Adverse Events (TAE)249/3184 = 7.8% (placebo 6.2% RR 1.37)*Arterial TAE OR 1.5 (95%CI 0.93-2.41)Venous TAE OR 0.76 (95% CI 0.49-1.15)*Trend toward statistical significance (>5%incidence in the elderly > 65.)
  • Efficacy for reversal in ICHHemostatic Drug Therapies for Acute SpontaneousIntracerebral Hemorrhage. Cochrane Database ofSystem Rev 2009.Death 18.5% (rFVIIa) vs 19.4% (Placebo) RR 0.85Death and/or Dependence 49.6% vs 51.7% RR 0.91Essentially ineffective when looking at outcomes likeMortality, which is all that really matters.
  • The ER coagulationcascade Tissue Damage OTHER FACTORS V, VIII, IX, XI, XII 1.FACTOR VIIa NOVO 7 2.FACTOR Xa ==FACTOR X 3.PROTHROMBIN== THROMBIN PRADAXA FIBRONGEN ==FIBRIN CLOTS
  • FEIBA Activated Prothrombin Complex Concentrates (II, VII, IX, and X) Dose 500U -1000U Often repeated for sustained effect up to 2000Units Cost $1.59U/1000U = $1600/dose Typically 1-3 doses given
  • SafetyCezary et al. Activated prothrombin complex concentratefactor VIII inhibitor bypassing activity (FEIBA) for thereversal of warfarin-induced coagulopathy. Int J EmergMed 2009.Complications:4/72 or 7% (1 peri-operative MI, 1 thrombosis ofCVC, 2 NSTEMI) VERY conservative.
  • FEIBA EfficacyFEIBA used in warfarin reversal:72 patients with life-threatening bleeds on coumadin.54% Had INR < 1.4, vs 30% of patients who receivedFFP.No mortality benefit, reduced hematoma expansionafter ICH, rapid reversal of INR immediately (<15minutes)
  • The ER coagulationcascade Tissue Damage OTHER FACTORS V, VIII, IX, XI, XII 1.FACTOR VIIa FEIBA 2.FACTOR Xa ==FACTOR X 3.PROTHROMBIN== THROMBIN PRADAXA FIBRONGEN ==FIBRIN CLOTS
  • Recommendations Evidence is poor Really endpoints like mortality are lacking No good RCT comparing these options exist. Head bleeds are bad, GI bleeds are better, and maybe reversing people doesn’t do anything at all.
  • In light of good evidence1. Pradaxa: check aPTT, if < 1.5normal = DONE- FEIBA 500U- rFVIIa 90mch/kg X 1 or about 1mg- FFP and HEMODIALYSIS (if you can find someone to dialyze them)- Activated Charcoal if within 2 hours of ingestion2. Rivoroxaban:- PCC’s 50U/kg Profilnine- FEIBA 500-1000U3. Warfarin- FFP 15-20cc/kg minimum of 4U- PCC’s > FFP for time to reversal (cost is similar)- We have FEIBA (cost is more but rapidly reduces reversal time)
  • THANKS!!!