Prothrombin Complex Concentrate-4 Factor (Kcentra, Beriplex, Confidex)

Indications

Hemorrhage in Patients with Critical Illnesses or Severe Liver Disease Involving Deficiency of Vitamin K-Dependent Coagulation Factors (see End-Stage Liver Disease, [[End-Stage Liver Disease]])

  • xxxx

Reversal of Apixaban (Eliquis)-Associated Coagulopathy (see Apixaban, [[Apixaban]]) (Biomed Res Int, 2014) [MEDLINE]

  • xxx

Reversal of Coumadin-Associated Coagulopathy (see Coumadin, [[Coumadin]])

  • Clinical Efficacy
    • Trial Comparing PCC to FFP in the Correction of INR in Coumadin-Associated Hemorrhage (Circulation, 2013) [MEDLINE]: PCC-4 factor was superior to FFP in terms of achieving rapid INR correction
    • Randomized, Non-Inferiority Trial Comparing Prothrombin Complex Concentrate-4 Factor vs Fresh Frozen Plasma in Reversing Coumadin (Lancet, 2015) [MEDLINE]: prothrombin complex concentrate-4 factor achieved effective hemostasis in 90% of subjects, as compared to 75% in the plasma group
    • Safety Profile (Thromboembolic Events, Fluid Overload, and Late Bleeding Events): similar in the two groups
  • Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
    • For Coumadin Anticoagulation with Associated Major Hemorrhage, Prothrombin Complex Concentrate-4 Factor is Recommended Over Fresh Frozen Plasma (Grade 2C Recommendation)
      • Intravenous Vitamin K (5-10 mg IV) is Also Recommended: see below
  • Recommendations (Neurocritical Care Society and Society of Critical Care Medicine Guidelines for Reversal of Antithrombotics in the Setting of Intracranial Hemorrhage, 2016) [MEDLINE]
    • Vitamin K (10 mg IV) is Recommended
    • Prothrombin Complex Concentrate-3 Factor or Prothrombin Complex Concentrate-3 Factor are Recommended Over FFP or Factor VIIa (Conditional Recommendation, Low Quality Evidence)
      • Prothrombin Complex Concentrate-4 Factor is Recommended Over Prothrombin Complex Concentrate-3 Factor (Conditional Recommendation, Low Quality Evidence)

Reversal of Rivaroxaban (Xarelto)-Associated Coagulopathy (see Rivaroxaban, [[Rivaroxaban]]) (Biomed Res Int, 2014) [MEDLINE]

  • xxx

Contraindications


Pharmacology

  • Content: human plasma-derived
    • Factor II (approximaely 25x more concentrated than are present in plasma): procoagulant, vitamin K-dependent
    • Factor VII (approximaely 25x more concentrated than are present in plasma): procoagulant, vitamin K-dependent
    • Factor IX (approximaely 25x more concentrated than are present in plasma): procoagulant, vitamin K-dependent
    • Factor X (approximaely 25x more concentrated than are present in plasma): procoagulant, vitamin K-dependent
    • Protein C: anticoagulant, vitamin K-dependent
    • Protein S: anticoagulant, vitamin K-dependent
  • Clinical Effect: a single Kcentra infusion produces a rapid and sustained increase in plasma concentration of factors II, VII, IX, and X within 30 min

Administration

  • IV
    • Mean infusion time with Kcentra is 7x faster than with fresh frozen plasma (mean duration 24 min vs almost 3 hrs)
    • Requires 87% less volume than fresh frozen plasma
    • Does not require thawing or blood-type matching

Dose Adjustment

  • Hepatic:
  • Renal:

Adverse Effects

Cardiovascular Adverse Effects

Neurologic Adverse Effects

Gastrointestinal Adverse Effects

Hematologic Adverse Effects

Other Adverse Effects

  • Arthralgias (see Arthralgias, [[Arthralgias]])
  • Transmission of Infectious Agents: as Kcentra is derived from human plasma, the risk of transmission of infectious agents (including viruses and Creutzfeldt-Jakob disease agent) cannot be completely eliminated

References

  • Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma- controlled, phase IIIb study. Circulation. 2013;128:1234–43 [MEDLINE]
  • Outcomes of urgent warfarin reversal with frozen plasma versus prothrombin complex concentrate in the emergency department. Circulation. 2013 Jul 23;128(4):360-4. doi: 10.1161/CIRCULATIONAHA.113.001875. Epub 2013 Jun 14 [MEDLINE]
  • Management of the bleeding patient receiving new oral anticoagulants: a role for prothrombin complex concentrates. BioMed Res Int. 2014; Article ID 583794 [MEDLINE]
  • Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet 2015 May 23;385(9982):2077-87. doi: 10.1016/S0140-6736(14)61685-8. Epub 2015 Feb 27 [MEDLINE]
  • Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016 Feb;149(2):315-52. doi: 10.1016/j.chest.2015.11.026. Epub 2016 Jan 7 [MEDLINE]
  • Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage: A Statement for Healthcare Professionals from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care. 2016 Feb;24(1):6-46. doi: 10.1007/s12028-015-0222-x [MEDLINE]