Kcentra Presentation
Download
Report
Transcript Kcentra Presentation
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. Accessed on 11/7/14.
4. Lexi-Comp, Inc. (Lexi-Drugs). Lexi-Comp, Inc.;January 29, 2015.
5. Tanaka KA, Szlam F. Treatment of massive bleeding with prothrombin complex concentrate: argument for. J Thromb Haemost.
2010;8:2589-91.
6. Godier A, Susen S, Samama C-M. Tanaka KA, Szlam F. Treatment of massive bleeding with prothrombin complex concentrate:
argument against. J Thromb Haemost. 2010;8:2592-95
7. Holbrook A, Schulman S, Witt DM, et al. Evidence-Based Management of Anticoagulant Therapy. Antithrombotic Therapy and
Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest.
2012;141(2)(Suppl):e152S-e184S.
8. Nutescu EA, Dager WE, Kalus JS, Lewin JJ, Cipolle MD. Management of bleeding and reversal strategies for oral anticoagulants:
Clinical Practice Considerations. Am J Health-Syst Pharm. 2013;70:1914-1929.
9. Tran H, et al. New oral anticoagulants: a practical guide on prescription, laboratory testing and peri-procedural/ bleeding
management. Int Med J. 2014;44:525-536.
10. Dager WE, Gosselin RC, Roberts AJ. Reversing dabigatran in life-threatening bleeding occurring during cardiac ablation with factor
eight bypassing activity. Crit Care Med. 2013; 41(1):e42-46.
11. Grottke O, van Ryn J, Sprink HMH, Rossaint R. Prothrombin complex concentrates and a specific antidose to dabigatran are
effective ex-vivo in reversing the effects of dabigatran in an anticoagulation/liver trauma experimental model. Crit Care. 2014;18:R27.
12. Dickneite G. Prothrombin Complex Concentrates as Reversal Agents for New Oral Anticoagulants: lessons from preclinical studies
with Beriplex. Clin Lab Med. 2014;34:623-635.
References, cont.
13. Hiippala ST, Mllyla GJ, Vahtera EM. Hemostatic Factors and Replacement of Major Blood Loss with Plasma-Poor Red Cell
Concentrates. Anesth Analg. 1995;81:360-5.
14. Rourke C, et al. Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient
outcomes. J Thromb Haemost. 2012;10:1342-51.
15. Sorensen B, Fries D. Emerging treatment strategies for trauma-induced coagulopathy. Brit J Surg. 2012;99(Suppl1): 40-50.
16. Spahn DR, et al. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care.
2013;17:R76.
17. Kozek-Langenecker SA, et al. Management of severe perioperative bleeding. Guidelines from the European Society of
Anaesthesiology. Eur J Anaesthesiol. 2013;30:270-382.
18. Fries D. The early use of fibrinogen, prothrombin complex concentrate, and recombinant-activated factor VIIa in massive bleeding.
Transfusion. 2013;53(s):91s-95s.
19. Tanaka KA, Esper S, Bolliger D. Perioperative factor concentrate therapy. Brit J Anaesth. 2013;111(S1): i35-i49.
20. Schochl H, Grassetto A, Schlimp CJ. Management of Hemorrhage in Trauma. J Cardiothor Vasc Anesth. 2013;27(4): S35-S43.
21. Franchini M, Lippi G. Prothrombin complex concentrates: an update. Blood Transfus. 2010;8:149-54.
22. Joseph B, et al. Factor IX complex for the correction of traumatic coagulopathy. J Trauma. 2010;72(4):828-834.
23. Schick KS, Fertmann JM, Jauch KW, Hoffmann JN. Prothrombin complex concentrates in surgical patients: retrospective evaluation
of vitamin K antagonist reversal and treatment of severe bleeding. Crit Care. 2009;13:R191.
24. Carvalho MC, Rodrigues AG, Conceicao LM, Galvao ML, Ribeiro LC. Prothrombin complex concentrate (Octaplex): a Portuguese
experience in 1152 patients. Blood Coag Fibrin. 2012;23:222-228.
25. Lorenz R, et al. Efficacy and safety of a prothrombin complex concentrate [Beriplex] with two virus-inactivation steps in patients with
severe liver damage. Eur J Gastroenterol Hepatol. 2003;15:15-20.
26. Hilbert P, et al. The “Coagulation Box” and a New Hemoglobin-Driven Algorithm for Bleeding Control in Patients with Severe Multiple
Traumas. Arch Trauma Res. 2013;2(1):1-10.
27. Majeed A, Eelde A, Agren A, et al. Thromboembolic safety and efficacy of prothrombin complex concentrates in the emergent
reversal of warfarin coagulopathy. Thromb Res. 2012;129:146-51.
28. Innerhofer P, et al. The exclusive use of coagulation factor concentrates enables reversal of coagulopathy and decreases transfusion
rates in patients with major blunt trauma. Injury, Int J Care Injured. 2013;44:209-216.