Denise H Rhoney1, Mary La2, Molly Merz2, Aaron Cook3, Kent A Owusu4, Christina Roels5, Joe Blunck6, Justin Shewmaker6, Kiranpal S Sangha7, Salia Farrokh8, John Lewin8, Kathleen W Chester9, Theresea Human10, Kathleen Bledsoe11, Kristy Greene12, Melissa Levesque13, Jody C Rocker14, Gary Davis15, Ron Neyens16, Timothy F Lassiter17, Sarah M Adriance18. 1. University of North Carolina Eshelman School of Pharmacy, 115E Beard Hall, Campus Box 7574, Chapel Hill, NC, 27599-7574, USA. drhoney@unc.edu. 2. University of North Carolina Eshelman School of Pharmacy, 115E Beard Hall, Campus Box 7574, Chapel Hill, NC, 27599-7574, USA. 3. University of Kentucky Medical Center, Lexington, KY, USA. 4. Yale-New Haven Hospital, New Haven, CT, USA. 5. Novant Health Forsyth Medical Center, Winston Salem, NC, USA. 6. St. Lukes Hospital, Kansas City, MO, USA. 7. University of Cincinnati Medical Center, Cincinnati, OH, USA. 8. Johns Hopkins Hospital, Baltimore, MD, USA. 9. Grady Health System, Atlanta, GA, USA. 10. Barnes Jewish Hospital, St. Louis, MO, USA. 11. University of Virginia Health System, Charlottesville, VA, USA. 12. Emory University Hospital Midtown, Atlanta, GA, USA. 13. Tampa General Hospital, Tampa, FL, USA. 14. Augusta University Medical Center, Augusta, GA, USA. 15. University of Utah Health, Salt Lake, UT, USA. 16. Medical University of South Carolina Medical Center, Charleston, SC, USA. 17. Duke University Hospital, Durham, NC, USA. 18. The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Abstract
BACKGROUND/ OBJECTIVE: Inactivated four-factor prothrombin complex concentrate (I4F-PCC, Kcentra®) has become an important agent for the urgent or emergent reversal of bleeding associated with vitamin K antagonists such as warfarin. There is recognized inter-institutional variability with the use of I4F-PCC, especially as it relates to dosing practices. We sought to characterize variations in I4F-PCC dosing practices and their impact on patient outcomes and describe overall real-world clinical practice surrounding I4F-PCC utilization in the context of the management of warfarin-related intracranial hemorrhage (ICH). METHODS: This is a multicenter retrospective pragmatic registry study of adult patients admitted at a participating study site between January 1, 2014, and December 31, 2015, who received I4F-PCC for reversal of warfarin-related ICH. Practices around warfarin-related ICH reversal in context of I4F-PCC utilization are described, including repeat I4F-PCC dosing, adjunctive reversal agents, and dose rounding policies (i.e., rounding doses to nearest vial size vs preparing exact/unrounded doses). All research was approved by local human investigation committees at each institution. RESULTS: Seventeen institutions contributed data on 528 patients to this registry. These institutions were primarily urban centers (74%), located in the southeast USA (47%), with Level 1 Trauma designation (79%), and with Comprehensive Stroke Center designation (74%). Most patients included in the study had sustained a non-traumatic ICH (68%), had a median admission GCS of 14 (IQR 7-15), and were receiving warfarin for atrial fibrillation (57.4%). There was substantial time latency between baseline INR and I4F-PCC (median 2.4 h, IQR 1.4-4.5 h). Most patients received adjunctive reversal agents, including vitamin K (89.5%) and fresh frozen plasma (FFP) (31.9%). A smaller proportion (6.0%) of patients received repeat I4F-PCC dosing. The median ICU length of stay (LOS) was 3 days (IQR 2-7 days), median hospital LOS was 6 days (IQR 3-12 days), and overall mortality rate was 28.8%. For institutions rounding doses to the nearest vial size, the first post-I4F-PCC dose INR was statistically but not clinically significantly lower than for institutions without vial size dose rounding, with comparable degrees of INR reduction from baseline. No differences were observed between dose rounding cohorts in adverse effects, ICU or hospital LOS, modified Rankin score at discharge, or mortality rates. CONCLUSIONS: Most patients received single doses of I4F-PCC, with adjunctive reversal agents and rounding doses to vial size. The time difference from baseline INR to factor product administration is a potential opportunity for process improvement in the management of warfarin-related ICH.
BACKGROUND/ OBJECTIVE: Inactivated four-factor prothrombin complex concentrate (I4F-PCC, Kcentra®) has become an important agent for the urgent or emergent reversal of bleeding associated with vitamin K antagonists such as warfarin. There is recognized inter-institutional variability with the use of I4F-PCC, especially as it relates to dosing practices. We sought to characterize variations in I4F-PCC dosing practices and their impact on patient outcomes and describe overall real-world clinical practice surrounding I4F-PCC utilization in the context of the management of warfarin-related intracranial hemorrhage (ICH). METHODS: This is a multicenter retrospective pragmatic registry study of adult patients admitted at a participating study site between January 1, 2014, and December 31, 2015, who received I4F-PCC for reversal of warfarin-related ICH. Practices around warfarin-related ICH reversal in context of I4F-PCC utilization are described, including repeat I4F-PCC dosing, adjunctive reversal agents, and dose rounding policies (i.e., rounding doses to nearest vial size vs preparing exact/unrounded doses). All research was approved by local human investigation committees at each institution. RESULTS: Seventeen institutions contributed data on 528 patients to this registry. These institutions were primarily urban centers (74%), located in the southeast USA (47%), with Level 1 Trauma designation (79%), and with Comprehensive Stroke Center designation (74%). Most patients included in the study had sustained a non-traumatic ICH (68%), had a median admission GCS of 14 (IQR 7-15), and were receiving warfarin for atrial fibrillation (57.4%). There was substantial time latency between baseline INR and I4F-PCC (median 2.4 h, IQR 1.4-4.5 h). Most patients received adjunctive reversal agents, including vitamin K (89.5%) and fresh frozen plasma (FFP) (31.9%). A smaller proportion (6.0%) of patients received repeat I4F-PCC dosing. The median ICU length of stay (LOS) was 3 days (IQR 2-7 days), median hospital LOS was 6 days (IQR 3-12 days), and overall mortality rate was 28.8%. For institutions rounding doses to the nearest vial size, the first post-I4F-PCC dose INR was statistically but not clinically significantly lower than for institutions without vial size dose rounding, with comparable degrees of INR reduction from baseline. No differences were observed between dose rounding cohorts in adverse effects, ICU or hospital LOS, modified Rankin score at discharge, or mortality rates. CONCLUSIONS: Most patients received single doses of I4F-PCC, with adjunctive reversal agents and rounding doses to vial size. The time difference from baseline INR to factor product administration is a potential opportunity for process improvement in the management of warfarin-related ICH.
Authors: Joshua N Goldstein; Majed A Refaai; Truman J Milling; Brandon Lewis; Robert Goldberg-Alberts; Bruce A Hug; Ravi Sarode Journal: Lancet Date: 2015-02-27 Impact factor: 79.321
Authors: Paul A Harris; Robert Taylor; Robert Thielke; Jonathon Payne; Nathaniel Gonzalez; Jose G Conde Journal: J Biomed Inform Date: 2008-09-30 Impact factor: 6.317
Authors: Allison E Berndtson; Wan-Ting Huang; Kevin Box; Leslie Kobayashi; Laura N Godat; Alan M Smith; David Weingarten; Raul Coimbra Journal: J Trauma Acute Care Surg Date: 2015-12 Impact factor: 3.313