title: Fixed Versus Variable Dosing of Prothrombin Complex Concentrate in Vitamin K Antagonist-Related Intracranial Hemorrhage: A Retrospective Analysis.
abstract: Millions of patients receive vitamin K antagonist (VKA) therapy worldwide. Annually 0.2-1 % of all VKA users develops an intracranial hemorrhage (ICH). Prothrombin complex concentrate (PCC) is administered to restore the INR ≤ 1.5 in an attempt to limit hematoma growth. In order to facilitate PCC dosing, our hospital recently changed from a variable dose based on bodyweight, baseline- and target-INR, to a fixed 1000 IU fIX PCC dosing protocol for ICH.
  
  
  
  In a before and after design, we compared successful achievement of an INR ≤ 1.5 with a fixed dosing strategy versus the variable dosing strategy of PCC in patients presenting with intracranial bleeding complications of VKA. Data of the two cohorts of patients were retrospectively collected from medical records.
  
  
  
  A median dosage of 1750 IU was given per patient in the variable dose group (n = 25) versus 1000 IU in the fixed dose group (n = 28). In the intention-to-treat analysis, 96 % achieved an INR ≤ 1.5 after an initial dose in the variable dose cohort compared to 68 % in the fixed dose cohort (p = 0.01). An additional dose was given in 2 (8 %) versus 9 (32 %) patients, respectively (p = 0.04). The median door-to-PCC-order time was 42 versus 32 min (p = 0.37) and the door-to-needle time was 81, respectively 60 min (p = 0.42).
  
  
  
  The fixed dose protocol necessitates additional PCC infusions more frequently to achieve a target INR ≤ 1.5. Door-to-order and door-to-needle time were shorter but, in this small cohort, not significantly so. The effect on clinical outcome remains unknown.
authors.affiliation: Department of Haematology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. r.abdoellakhan@ahz.nl.|Department of Pharmacy, Apotheek Haagse Ziekenhuizen, The Hague, The Netherlands. r.abdoellakhan@ahz.nl.
authors.forename: Rahat Amadkhan
authors.initials: RA
authors.lastname: Abdoellakhan
authors.affiliation: Department of Neurology, Medical Center Haaglanden, The Hague, The Netherlands.
authors.forename: Ishita Parveen
authors.initials: IP
authors.lastname: Miah
authors.affiliation: Department of Pharmacy, Apotheek Haagse Ziekenhuizen, The Hague, The Netherlands.
authors.forename: Nakisa
authors.initials: N
authors.lastname: Khorsand
authors.affiliation: Department of Haematology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Karina
authors.initials: K
authors.lastname: Meijer
authors.affiliation: Department of Neurology, Medical Center Haaglanden, The Hague, The Netherlands.
authors.forename: Korné
authors.initials: K
authors.lastname: Jellema
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D001779:Blood Coagulation Factors / Q000008:administration & dosage*; 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; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D014812:Vitamin K; C025667:prothrombin complex concentrates
keywords: Hemostasis; International normalized ratio; Intracranial hemorrhage; Prothrombin complex concentrate; Vitamin K antagonist