title: Safety and Efficacy of Warfarin Reversal with Four-Factor Prothrombin Complex Concentrate for Subtherapeutic INR in Intracerebral Hemorrhage.
abstract: The use of vitamin K antagonists is an independent risk factor for the development of intracerebral hemorrhage (ICH). Four-factor prothrombin complex concentrate (4F-PCC) is recommended for urgent reversal of anticoagulation in this setting. The safety and efficacy of 4F-PCC in ICH with subtherapeutic levels of anticoagulation is yet to be determined.
  
  
  
  This was a retrospective, observational study of 4F-PCC administration data from September 2013 to July 2015. Patients with spontaneous or traumatic ICH with initial INR 1.4-1.9 were compared to those with INR 2-3.9. A Fisher's exact test was used to compare the difference between the two groups in the effectiveness of 4F-PCC in reversing the INR to ≤1.3 and in the occurrence of thrombotic events within 7 days of administration.
  
  
  
  A total of 131 patients with a presenting INR between 1.4 and 3.9 received 4F-PCC during the study period. Twenty-three of 29 patients (79 %) in the INR <2 group achieved an INR reduction to ≤1.3 after 4F-PCC administration compared to 47 of 92 patients (51 %) in the INR 2-4 group, p = 0.03. There was no difference in thrombotic complications within 7 days after administration (6.7 % in INR 1.4-1.9 group, 10 % in INR 2-3.9 group, p = 0.73).
  
  
  
  The use of 4F-PCC in patients with INR between 1.4 and 1.9 results in an effective reduction in INR with similar thrombotic risks compared to patients presenting with an INR of 2-3.9.
authors.affiliation: Department of Pharmacy, UPMC Presbyterian Hospital, Pittsburgh, PA, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Rivosecchi
authors.affiliation: Department of Pharmacy, UPMC Presbyterian Hospital, Pittsburgh, PA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Durkin
authors.affiliation: Department of Neurologic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: David O
authors.initials: DO
authors.lastname: Okonkwo
authors.affiliation: Departments of Neurology and Critical Care Medicine, University of Pittsburgh, 3501 Fifth Avenue, BST3-7021, Pittsburgh, PA, 15213, USA. moly@pitt.edu.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Molyneaux
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D001779:Blood Coagulation Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D012189:Retrospective Studies; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D014859:Warfarin
keywords: Anticoagulants; Cerebral hemorrhage; Prothrombin complex concentrates; Vitamin K antagonist