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
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Define PCC
Differentiate PCCs available in US
Identify action in coagulation cascade
Compare Kcentra with FFP
Review use of Kcentra in trauma:
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Emergent reversal of oral anticoagulants
Management of trauma hemorrhage
Discuss Kcentra nursing considerations
What are PCCs?
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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
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4f-PCC
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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
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Dilutional coagulopathy
Risk of transfusion-related
acute lung injury
Emergent Warfarin

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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?
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? FEIBA 25 un/kg10
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aDabi-Fab (future)11
Management of Trauma
Hemorrhage – Standards of Care16
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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
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Risk factors for low fibrinogen level on admission14:
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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
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Evidence-supported benefit?
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Thrombosis risk: low (0-1.4% for current 4fPCCs)
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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:
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Massive hemorrhage unresponsive to conventional tx
TEG-guided: ongoing bleed with CT > 90s15
Hgb-driven “Coagulation Box” model: Hgb < 5.526
Kcentra – Nursing Considerations
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Verbal orders
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Clarify which “PCC”, what un/kg dose (fIX), indication
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Contact blood bank or pharmacy to alert of STAT order
Administration
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Concentration, dose and rate vary (~10-20 min)
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Emergent reversal. Give ASAP (expires 4hrs after mixed)
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Document lot numbers (blood product)
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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.