title: Obesity increases risk of anticoagulation reversal failure with prothrombin complex concentrate in those with intracranial hemorrhage.
abstract: BACKGROUND
  Not all patients with warfarin-related acute intracranial hemorrhage (ICH) achieve full reversal of international normalized ratio (INR) after the first dose of weight-based prothrombin complex concentrate (PCC). We sought to identify factors associated with anticoagulation reversal failure after the first dose of PCC.
  
  
  METHODS
  Consecutive patients who were hospitalized with warfarin-related acute ICH at a tertiary center between 1 January 2010 and 31 December 2012 were studied. Anticoagulation reversal failure was defined as INR ≥ 1.5 after the first dose of PCC. Logistic regression was performed to determine the predictors of anticoagulation reversal failure.
  
  
  RESULTS
  Fifty-one patients with acute ICH received PCC for warfarin reversal using a weight-based protocol. Overall, 23 (45%) patients did not achieve full reversal of INR after the first dose. Those with anticoagulation reversal failure were obese (body mass index > 30 kg/m(2)) (41% vs. 14%, p = 0.03), had a higher initial INR (3.0 ± 1.4 vs. 2.0 ± 0.7, p = 0.001), and had a higher prevalence of initial INR >2.0 (22% vs. 67%, p = 0.001), compared with those who were successfully reversed. Multivariable logistic regression identified obesity (odds ratio 7.88, 95% CI 1.12 to 55.68) and initial INR >2.0 (odds ratio 12.49, 95% CI 2.27 to 68.87) as independent predictors of anticoagulation reversal failure.
  
  
  CONCLUSIONS
  Obesity and elevated initial INR are independently associated with anticoagulation reversal failure using the weight-based PCC protocol in patients with warfarin-related acute ICH. Further studies are needed to determine more effective dosing protocols and individualized strategies for anticoagulation reversal after acute ICH, especially among obese patients.
authors.affiliation: a Department of Pharmacy Practice, Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Honolulu, HI, USA.
authors.forename: Cherie
authors.initials: C
authors.lastname: Chu
authors.affiliation: a Department of Pharmacy Practice, Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, Honolulu, HI, USA.
authors.forename: Sheri
authors.initials: S
authors.lastname: Tokumaru
authors.affiliation: b Department of Pharmacy, The Queen's Medical Center, Honolulu, HI, USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Izumi
authors.affiliation: c Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA, and Department of Neuroscience, The Queen's Medical Center, Honolulu, HI, USA.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D015992:Body Mass Index; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009765:Obesity / Q000097:blood / Q000150:complications*; D012189:Retrospective Studies; D012306:Risk; D017211:Treatment Failure; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D014859:Warfarin
keywords: obesity; prothrombin complex concentrate; warfarin