Emergent reversal

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Emergent reversal

  1. 1. David Barounis R-2Advocate Christ Medical Center
  2. 2. 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??
  3. 3. 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?
  4. 4. 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??
  5. 5. 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?
  6. 6. 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
  7. 7. Coagulation Cascade
  8. 8. Coagulation Cascade
  9. 9. 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
  10. 10. 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
  11. 11. 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
  12. 12. Dabigatran(Pradaxa) Direct Thrombin Inhibitor Approved for anti-coagulation in patients with non-valvular atrial fibrillation RE-LY trial comparing coumadin to Dabigatran
  13. 13. 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
  14. 14. 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
  15. 15. 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
  16. 16. PCC’s Safety*1.4% complication rate (3 CVA, 2 DVT, and 2 non Q wave MI’s)
  17. 17. 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
  18. 18. 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!!!
  19. 19. 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)
  20. 20. 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.)
  21. 21. 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.
  22. 22. 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
  23. 23. 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
  24. 24. 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.
  25. 25. 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)
  26. 26. 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
  27. 27. 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.
  28. 28. 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)
  29. 29. THANKS!!!
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