title: Risk of thromboembolic events after protocolized warfarin reversal with 3-factor PCC and factor VIIa.
abstract: Bleeding events and life-threatening hemorrhage are the most feared complications of warfarin therapy. Prompt anticoagulant reversal aimed at replacement of vitamin K-dependent clotting factors is essential to promote hemostasis. A retrospective cohort study of warfarin-treated patients experiencing a life-threatening hemorrhage treated with an institution-specific warfarin reversal protocol (postimplementation group) and those who received the prior standard of care (preimplementation group) was performed. The reversal protocol included vitamin K, 3-factor prothrombin complex concentrate, and recombinant factor VIIa. Demographic and clinical information, anticoagulant reversal information, and all adverse events attributed to warfarin reversal were recorded. A total of 227 patients were included in final analysis, 109 in the preimplementation group and 118 in the postimplementation group. Baseline patient characteristics were similar in both groups, with the exception of higher average Sequential Organ Failure Assessment scores in the postimplementation group (P = .0005). The most common indication for anticoagulation reversal was intraparenchymal hemorrhage. Prereversal international normalized ratios (INRs) were similar in both groups. Attainment of INR normalization to less than 1.4 was higher, and rebound INR was lower in the postimplementation group (P < .0001; P = .0013). Thromboembolic complications were significantly higher in the postimplementation group (P = .003). Elevated baseline Sequential Organ Failure Assessment score and mechanical valve as an indication for anticoagulation were independently associated with thrombotic complications (P = .005). A warfarin reversal protocol consisting of 3-factor prothrombin complex concentrate, recombinant factor VIIa, and vitamin K more consistently normalized INR values to less than 1.4 as compared to the prior standard of care in a diverse patient population. This success came at the cost of a 2-fold increase in risk of thromboembolic complications.
authors.affiliation: Department of Pharmacy, Oregon Health & Science University, Portland, OR 97239. Electronic address: bartonc@ohsu.edu.
authors.forename: Cassie A
authors.initials: CA
authors.lastname: Barton
authors.affiliation: Department of Pharmacy, Oregon Health & Science University, Portland, OR 97239. Electronic address: johnatha@ohsu.edu.
authors.forename: Nathan B
authors.initials: NB
authors.lastname: Johnson
authors.affiliation: Department of Pharmacy, Oregon Health & Science University, Portland, OR 97239. Electronic address: casejo@ohsu.edu.
authors.forename: Jon
authors.initials: J
authors.lastname: Case
authors.affiliation: Department of Pharmacy, Oregon Health & Science University, Portland, OR 97239. Electronic address: warden@ohsu.edu.
authors.forename: Bruce
authors.initials: B
authors.lastname: Warden
authors.affiliation: Department of Pharmacy, University Health System and Department of Emergency Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX 78229. Electronic address: Darrel.Hughes@uhs-sa.com.
authors.forename: Darrel
authors.initials: D
authors.lastname: Hughes
authors.affiliation: Department of Pharmacy, Oregon Health & Science University, Portland, OR 97239. Electronic address: zimmerja@ohsu.edu.
authors.forename: Jason
authors.initials: J
authors.lastname: Zimmerman
authors.affiliation: Department of Pharmacy, Oregon Health & Science University, Portland, OR 97239. Electronic address: robertig@ohsu.edu.
authors.forename: Gregory
authors.initials: G
authors.lastname: Roberti
authors.affiliation: Department of Pharmacy, University of Vermont Medical Center, Burlington, VT 05402. Electronic address: wes.mcmillian@uvmhealth.org.
authors.forename: Wesley D
authors.initials: WD
authors.lastname: McMillian
authors.affiliation: Department of Surgery, Oregon Health & Science University, Portland, OR 97239. Electronic address: schreibm@ohsu.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Schreiber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D002985:Clinical Protocols; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005164:Factor IX / Q000009:adverse effects* / Q000627:therapeutic use; D005167:Factor VII / Q000009:adverse effects* / Q000627:therapeutic use; D015942:Factor VIIa / Q000009:adverse effects* / Q000627:therapeutic use; D005170:Factor X / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy*; D006490:Hemostatics / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D019934:International Normalized Ratio; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000009:adverse effects* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D013923:Thromboembolism / Q000139:chemically induced* / Q000517:prevention & control; D016896:Treatment Outcome; D014812:Vitamin K / Q000009:adverse effects / Q000627:therapeutic use; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D004338:Drug Combinations; D006490:Hemostatics; D011994:Recombinant Proteins; D014812:Vitamin K; D014859:Warfarin; D005167:Factor VII; D011516:Prothrombin; D005164:Factor IX; D005170:Factor X; C103587:recombinant FVIIa; D015942:Factor VIIa; C000599051:Profilnine SD