title: Evaluation of Warfarin Reversal with 4-Factor Prothrombin Complex Concentrate Compared to 3-Factor Prothrombin Complex Concentrate at a Tertiary Academic Medical Center.
abstract: BACKGROUND
  The U.S. Food and Drug Administration recently approved a four-factor prothrombin complex concentrate (4-PCC) for warfarin reversal. The literature supporting its use over three-factor prothrombin complex concentrate (3-PCC) is limited.
  
  
  OBJECTIVE
  Our objective was to retrospectively compare the efficacy of 3-PCC to 4-PCC in reversing warfarin in patients who were actively bleeding.
  
  
  METHODS
  We conducted a single-center, retrospective cohort analysis of adult patients who received 3-PCC or 4-PCC for international normalized ratio (INR) reversal. Our study excluded patients not actively bleeding and not on warfarin. The main outcome was the percentage of patients who achieved warfarin reversal defined as INR ≤ 1.3 at first INR check post factor administration. We recorded baseline data including PCC dose, location of bleed, pre- and posttreatment INR, and time to INR reversal.
  
  
  RESULTS
  We included a total of 53 patients. Intracranial hemorrhage was the most common site of bleeding (26 [74.3%] in 3-PCC vs. 12 [66.7%] in 4-PCC). The mean dose of 3-PCC was 25.5 units/kg, compared to 27.9 units/kg of 4-PCC. The mean baseline INR was 2.3 in the 3-PCC group and 3 in the 4-PCC group (p = 0.03), and the first posttreatment INRs were 1.4 and 1.2, respectively (p < 0.01). Warfarin reversal was achieved in 15 (42.9%) patients who received 3-PCC and 15 (83.3%) patients who received 4-PCC (p < 0.01). Faster time to INR reversal was noted in the 4-PCC group vs. the 3-PCC group (3.7 vs. 5 h, p = 0.48).
  
  
  CONCLUSIONS
  A higher percentage of patients achieved warfarin reversal with 4-PCC compared to 3-PCC treatment. A prospective randomized control trial is necessary to confirm our results.
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Omar
authors.initials: O
authors.lastname: Al-Majzoub
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Boston, Massachusetts; The Medicines Company, Parsippany, New Jersey.
authors.forename: Eva
authors.initials: E
authors.lastname: Rybak
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: David P
authors.initials: DP
authors.lastname: Reardon
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Patricia
authors.initials: P
authors.lastname: Krause
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Jean M
authors.initials: JM
authors.lastname: Connors
mesh_terms: D000046:Academic Medical Centers; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D001779:Blood Coagulation Factors / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D019934:International Normalized Ratio; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D012189:Retrospective Studies; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D014859:Warfarin
keywords: INR; anticoagulation reversal; prothrombin complex concentrate; warfarin