Off-label use of 4-factor prothrombin complex concentrate is common despite little known benefit: A retrospective study

Carlton D. Scharman, Joseph J. Shatzel, Edward Kim, Thomas Deloughery

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2 Citations (Scopus)

Abstract

Background/Objective: While four-factor prothrombin complex concentrate (4F-PCC) is FDA-approved for reversal of warfarin-induced major bleeding, its use in real-world settings is unclear. This study's objective was to identify indications leading to 4F-PCC use and associated outcomes at a single university hospital. Methods: This was a retrospective cohort study of patients receiving 4F-PCC over a 22-month period. A dose was "on-label" if given for reversal of warfarin-induced coagulopathy in patients with major bleeding or requiring urgent surgeries/procedures; other doses were "off-label". Results: A total of 165 doses of 4F-PCC in 154 patients were given. Sixty-one percent of doses were on-label, while 39% were off-label. Intracranial hemorrhage was the most common indication (55% of doses). On-label patients had significantly higher rate of INR normalization and survival to hospital discharge than off-label patients. There was no difference in time to INR normalization, time to hemostasis, or incidence of thromboembolic complications. Conclusions: Off-label use of 4F-PCC is likely common, occurring in nearly 40% of drug administrations at our center. Larger-scale prospective trials studying specific indications are needed for validation in off-label settings. Until such evidence is available, given potential harms historically displayed by off-label use of other hemostatic agents, limiting off-label 4F-PCC use is recommended.

Original languageEnglish (US)
JournalEuropean Journal of Haematology
DOIs
StateAccepted/In press - Jan 1 2018

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Off-Label Use
Retrospective Studies
International Normalized Ratio
Warfarin
Hemorrhage
Intracranial Hemorrhages
Patient Discharge
Hemostatics
Hemostasis
Cohort Studies
Survival
prothrombin complex concentrates
Incidence
Pharmaceutical Preparations

Keywords

  • Anticoagulants
  • Antidotes
  • Drug evaluation
  • Factor VIIa
  • Hemorrhage
  • Prothrombin complex concentrate

ASJC Scopus subject areas

  • Hematology

Cite this

@article{af8918f890094200a0aa0eb3ba322d10,
title = "Off-label use of 4-factor prothrombin complex concentrate is common despite little known benefit: A retrospective study",
abstract = "Background/Objective: While four-factor prothrombin complex concentrate (4F-PCC) is FDA-approved for reversal of warfarin-induced major bleeding, its use in real-world settings is unclear. This study's objective was to identify indications leading to 4F-PCC use and associated outcomes at a single university hospital. Methods: This was a retrospective cohort study of patients receiving 4F-PCC over a 22-month period. A dose was {"}on-label{"} if given for reversal of warfarin-induced coagulopathy in patients with major bleeding or requiring urgent surgeries/procedures; other doses were {"}off-label{"}. Results: A total of 165 doses of 4F-PCC in 154 patients were given. Sixty-one percent of doses were on-label, while 39{\%} were off-label. Intracranial hemorrhage was the most common indication (55{\%} of doses). On-label patients had significantly higher rate of INR normalization and survival to hospital discharge than off-label patients. There was no difference in time to INR normalization, time to hemostasis, or incidence of thromboembolic complications. Conclusions: Off-label use of 4F-PCC is likely common, occurring in nearly 40{\%} of drug administrations at our center. Larger-scale prospective trials studying specific indications are needed for validation in off-label settings. Until such evidence is available, given potential harms historically displayed by off-label use of other hemostatic agents, limiting off-label 4F-PCC use is recommended.",
keywords = "Anticoagulants, Antidotes, Drug evaluation, Factor VIIa, Hemorrhage, Prothrombin complex concentrate",
author = "Scharman, {Carlton D.} and Shatzel, {Joseph J.} and Edward Kim and Thomas Deloughery",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/ejh.13105",
language = "English (US)",
journal = "European Journal of Haematology",
issn = "0902-4441",
publisher = "Wiley-Blackwell",

}

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T1 - Off-label use of 4-factor prothrombin complex concentrate is common despite little known benefit

T2 - A retrospective study

AU - Scharman, Carlton D.

AU - Shatzel, Joseph J.

AU - Kim, Edward

AU - Deloughery, Thomas

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background/Objective: While four-factor prothrombin complex concentrate (4F-PCC) is FDA-approved for reversal of warfarin-induced major bleeding, its use in real-world settings is unclear. This study's objective was to identify indications leading to 4F-PCC use and associated outcomes at a single university hospital. Methods: This was a retrospective cohort study of patients receiving 4F-PCC over a 22-month period. A dose was "on-label" if given for reversal of warfarin-induced coagulopathy in patients with major bleeding or requiring urgent surgeries/procedures; other doses were "off-label". Results: A total of 165 doses of 4F-PCC in 154 patients were given. Sixty-one percent of doses were on-label, while 39% were off-label. Intracranial hemorrhage was the most common indication (55% of doses). On-label patients had significantly higher rate of INR normalization and survival to hospital discharge than off-label patients. There was no difference in time to INR normalization, time to hemostasis, or incidence of thromboembolic complications. Conclusions: Off-label use of 4F-PCC is likely common, occurring in nearly 40% of drug administrations at our center. Larger-scale prospective trials studying specific indications are needed for validation in off-label settings. Until such evidence is available, given potential harms historically displayed by off-label use of other hemostatic agents, limiting off-label 4F-PCC use is recommended.

AB - Background/Objective: While four-factor prothrombin complex concentrate (4F-PCC) is FDA-approved for reversal of warfarin-induced major bleeding, its use in real-world settings is unclear. This study's objective was to identify indications leading to 4F-PCC use and associated outcomes at a single university hospital. Methods: This was a retrospective cohort study of patients receiving 4F-PCC over a 22-month period. A dose was "on-label" if given for reversal of warfarin-induced coagulopathy in patients with major bleeding or requiring urgent surgeries/procedures; other doses were "off-label". Results: A total of 165 doses of 4F-PCC in 154 patients were given. Sixty-one percent of doses were on-label, while 39% were off-label. Intracranial hemorrhage was the most common indication (55% of doses). On-label patients had significantly higher rate of INR normalization and survival to hospital discharge than off-label patients. There was no difference in time to INR normalization, time to hemostasis, or incidence of thromboembolic complications. Conclusions: Off-label use of 4F-PCC is likely common, occurring in nearly 40% of drug administrations at our center. Larger-scale prospective trials studying specific indications are needed for validation in off-label settings. Until such evidence is available, given potential harms historically displayed by off-label use of other hemostatic agents, limiting off-label 4F-PCC use is recommended.

KW - Anticoagulants

KW - Antidotes

KW - Drug evaluation

KW - Factor VIIa

KW - Hemorrhage

KW - Prothrombin complex concentrate

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