title: An observational, prospective, two-cohort comparison of a fixed versus variable dosing strategy of prothrombin complex concentrate to counteract vitamin K antagonists in 240 bleeding emergencies.
abstract: BACKGROUND
  Despite years of experience with vitamin K antagonist-associated bleeding events, there is still no evidence to help identify the optimal treatment with prothrombin complex concentrates. Variable dosing and fixed dose strategies are being used. In this observational prospective two-cohort study, we aimed to assess the non-inferiority of a low fixed PCC dose (1,040 IU Factor IX) compared to the registered variable dosing regimen based on baseline International Normalized Rate, bodyweight, and target International Normalized Rate, to counteract vitamin K antagonists in a bleeding emergency in a daily clinical practice setting.
  
  
  METHODS
  Non-inferiority of the fixed prothrombin complex concentrate dose was hypothesized with a margin of 4%. Main end points were proportion of patients reaching the target International Normalized Rate (< 2.0) after prothrombin complex concentrate treatment, and successful clinical outcome.
  
  
  RESULTS
  Target International Normalized Rate was reached in 92% of the fixed dose patients (n=101) versus 95% of variable dose patients (n=139) resulting in a risk difference of -2.99% (90% CI: - 8.6 to 2.7) (non-inferiority not confirmed). Clinical outcome was successful in 96% and 88% of fixed versus variable dose, respectively, with a risk difference of 8.3% (90% CI: 2.7-13.9; non-inferiority confirmed).
  
  
  CONCLUSIONS
  Although a lower fixed prothrombin complex concentrate dose was associated with successful clinical outcome, fewer patients reached the target International Normalized Rate.
authors.affiliation: Haga Teaching Hospital, The Hague, The Netherlands. n.khorsand@hagaziekenhuis.nl
authors.forename: Nakisa
authors.initials: N
authors.lastname: Khorsand
authors.forename: Nic J G M
authors.initials: NJ
authors.lastname: Veeger
authors.forename: Reinier M
authors.initials: RM
authors.lastname: van Hest
authors.forename: Paula F
authors.initials: PF
authors.lastname: Ypma
authors.forename: Jeroen
authors.initials: J
authors.lastname: Heidt
authors.forename: Karina
authors.initials: K
authors.lastname: Meijer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D001779:Blood Coagulation Factors / Q000008:administration & dosage* / Q000009:adverse effects; D001835:Body Weight; D004630:Emergencies; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000188:drug therapy*; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D014812:Vitamin K; C025667:prothrombin complex concentrates