title: Fixed versus variable dose of prothrombin complex concentrate for counteracting vitamin K antagonist therapy.
abstract: BACKGROUND
  Although prothrombin complex concentrate (PCC) is often used to counteract vitamin K antagonist (VKA) therapy, evidence regarding the optimal dose for this indication is lacking. In Dutch hospitals, either a variable dose, based on body weight, target INR (international normalised ratio) and initial INR, or a fixed dose is used.
  
  
  OBJECTIVE
  In this observational, pilot study, the efficacy and feasibility of the fixed dose strategy compared to the variable dosing regimen, is investigated.
  
  
  METHODS
  Consecutive patients receiving PCC (Cofact®, Sanquin, Amsterdam) for VKA reversal because of a major non-cranial bleed or an invasive procedure were enrolled in two cohorts. Data were collected prospectively in the fixed dose group, cohort 1, and retrospectively in the variable dose regimen, cohort 2. Study endpoints were proportion of patients reaching target INR and successful clinical outcome.
  
  
  RESULTS
  Cohort 1 consisted of 35 and cohort 2 of 32 patients. Target INR was reached in 70% of patients in cohort 1 versus 81% in cohort 2 (P = 0·37). Successful clinical outcome was seen in 91% of patients in cohort 1 versus 94% in cohort 2 (P = 1·00). Median INR decreased from 4·7 to 1·8 with a median dosage of 1040 IU factor IX (F IX) in cohort 1 and from 4·7 to 1·6 with a median dosage of 1580 IU F IX in cohort 2.
  
  
  CONCLUSIONS
  This study suggests that a fixed dose of 1040 IU of F IX may be an effective way to rapidly counteract VKA therapy in our patient population and provides a basis for future research.
authors.affiliation: Department of Hospital Pharmacy, Medical Centre Haaglanden, The Hague, The Netherlands. N.Khorsand@hagaziekenhuis.nl
authors.forename: N
authors.initials: N
authors.lastname: Khorsand
authors.forename: N J G M
authors.initials: NJ
authors.lastname: Veeger
authors.forename: M
authors.initials: M
authors.lastname: Muller
authors.forename: J W P M
authors.initials: JW
authors.lastname: Overdiek
authors.forename: W
authors.initials: W
authors.lastname: Huisman
authors.forename: R M
authors.initials: RM
authors.lastname: van Hest
authors.forename: K
authors.initials: K
authors.lastname: Meijer
mesh_terms: D000074:Acenocoumarol / Q000009:adverse effects / Q000037:antagonists & inhibitors; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D000931:Antidotes / Q000008:administration & dosage* / Q000627:therapeutic use; D001779:Blood Coagulation Factors / Q000008:administration & dosage* / Q000627:therapeutic use; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010644:Phenprocoumon / Q000009:adverse effects / Q000037:antagonists & inhibitors; D011446:Prospective Studies; D012189:Retrospective Studies; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D014859:Warfarin / Q000009:adverse effects / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D000931:Antidotes; D001779:Blood Coagulation Factors; D014812:Vitamin K; C025667:prothrombin complex concentrates; D014859:Warfarin; D000074:Acenocoumarol; D010644:Phenprocoumon