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High versus low fixed-dose four factor-prothrombin complex concentrate for warfarin reversal in patients with intracranial hemorrhage

      Abstract

      Background

      Four-factor prothrombin complex concentrate 4F-PCC is the standard of care for warfarin reversal in patients with major bleed or requiring urgent surgery. Although the 4F-PCC dose is weight and international normalized ratio (INR) based, for practical purposes, a fixed-dose approach has been explored, especially for rapid reversal. We report our experience using two different fixed-dose 4F-PCC for warfarin reversal in patients presenting with intracranial hemorrhage (ICH).

      Study design and methods

      We completed a retrospective chart review comparing high (4000 units) versus low (2000 units) dose 4F-PCC by evaluating patient characteristics, laboratory data, and pre-and post-4F-PCC brain imaging.

      Results

      There was no significant difference between patient characteristics or INR correction (≤1.5) between the two groups. Eighty percent (12/15) of patients who received the low dose 4F-PCC had either improved or stable brain imaging as compared to 88% (14/16) of patients who received the high dose PCC. When the eight patients (4 from each arm of the study) who required neurosurgery were excluded, only two patients in each arm had worse imaging after 4F-PCC.

      Conclusion

      There was no significant difference between the INR correction and the brain imaging changes in patients with an ICH who received either the high or the low fixed-dose 4F-PCC for warfarin reversal.

      Keywords

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      References

        • Schulman S.
        • Beyth R.J.
        • Kearon C.
        • et al.
        Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition).
        Chest. 2008; 13 (257S–98S)
        • Kinard T.N.
        • Sarode R.
        Four factor prothrombin complex concentrate (human): review of the pharmacology and clinical application for vitamin K antagonist reversal.
        Expert Rev Cardiovasc Ther. 2014; 12: 417-427
        • Chai-Adisaksopha C.
        • Hillis C.
        • Siegal D.M.
        • et al.
        Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal: a systematic review and meta-analysis.
        Thromb Haemost. 2016; 116: 879-890
        • Ansell J.
        • Hirsh J.
        • Hylek E.
        • et al.
        Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition).
        Chest. 2008; 133: 160S-198S
        • Sarode R.
        • Milling T.J.
        • Refaai M.A.
        • et al.
        Efficacy and safety of four-factor prothrombin complex concentrate (4F-PCC) in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma controlled, phase IIIb study.
        Circulation. 2013; 128 (1234-43)
        • Goldstein J.N.
        • Refaai M.A.
        • Milling Jr, T.J.
        • et al.
        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; : 1-11
        • Abdoellakhan R.A.
        • Miah I.P.
        • Khorsand N.
        • et al.
        Fixed versus variable dosing of prothrombin complex concentrate in vitamin k antagonist-related intracranial hemorrhage: a retrospective analysis.
        Neurocrit Care. 2017; 26: 64-69
        • Klein L.
        • Peters J.
        • Miner J.
        • Gorlin J.
        • et al.
        Evaluation of fixed dose 4-factor prothrombin complex concentrate for emergent warfarin reversal.
        Am J Emerg Med. 2015; 33 (1213–8)
        • Hickey M.
        • Gatien M.
        • Taljaard M.
        • et al.
        Outcomes of urgent warfarin reversal with frozen plasma versus prothrombin complex concentrate in the emergency department.
        Circulation. 2013; 128: 360-364
        • Gorlin J.
        • Kinney S.
        • Fung M.K.
        • et al.
        Prothrombin complex concentrate for emergent reversal of warfarin: an international survey of hospital protocols.
        Vox Sang. 2017; 112: 595-597
        • Frontera J.A.
        • Lewin III, J.J.
        • Rabinstein A.A.
        • et al.
        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; 24: 6-46
        • Appleby N.
        • Groake E.
        • Crowley M.
        • et al.
        Reversal of warfarin anticoagulation using prothrombin complex concentrate at 25 IUkg−1: results of the RAPID study.
        Transfus Med. 2017; 27 (66–7)