title: The Australian and New Zealand Haemostasis Registry: ten years of data on off-licence use of recombinant activated factor VII.
abstract: BACKGROUND
  Recombinant activated factor VII (rFVIIa) has been widely used as an off-licence pan-haemostatic agent in patients with critical bleeding. However, outside the trauma setting, there is relatively little high quality evidence on the risks and benefits of this agent. The Haemostasis Registry was established to investigate the extent of use, dosing, safety and outcomes of patients after off-licence rFVIIa treatment of critical bleeding.
  
  
  METHODS
  The Registry recruited non-haemophiliac patients treated with rFVIIa from 2000-2009 (inclusive) in Australia and New Zealand. Detailed information was gathered on patients' demographics, context of bleeding, rFVIIa administration, laboratory results, blood component and other therapies, and outcomes. Outcome measures included subjectively assessed effect of rFVIIa on bleeding (response), adverse events (thromboembolic and other) and 28-day mortality.
  
  
  RESULTS
  The registry included 3,446 cases in 3,322 patients (median [IQR] age 56 [33-70] years, 65% (n=2,147) male). Clinical indications included cardiac surgery (45%), other surgery (18%), trauma (13%), medical bleeding (6%), liver disease (6%), and obstetric haemorrhage (5%). The median [IQR] dose was 91 [72-103] μg/kg and 77% received a single dose. Reduction or cessation of bleeding was reported in 74% and 28-day survival was 71% but outcomes varied depending on clinical context. pH strongly correlated with outcome measures; 81% of patients with pH <7.1 died. Approximately 11% of patients had thromboembolic adverse events. In multivariate analysis, pH prior to administration and bleeding context were independently associated with reported response to rFVIIa and 28-day mortality.
  
  
  CONCLUSIONS
  The Haemostasis Registry is the largest dataset of its kind and provides observational data on the off-licence use of rFVIIa over a 10-year period. It has been an invaluable resource for rigorously tracking adverse events and helping to inform clinical practice.
authors: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors: Amanda
authors: A
authors: Zatta
authors: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors: Zoe
authors: Z
authors: Mcquilten
authors: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia Australian Haemophilia Centre Directors' Organisation, Melbourne, Australia.
authors: Rangi
authors: R
authors: Kandane-Rathnayake
authors: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia Transfusion Medicine, Royal North Shore Hospital, Sydney, Australia.
authors: James
authors: J
authors: Isbister
authors: Haemophilia and Thrombosis Unit, Royal Prince Alfred Hospital, Sydney, Australia.
authors: Scott
authors: S
authors: Dunkley
authors: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors: John
authors: J
authors: Mcneil
authors: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia Emergency and Trauma Centre, Alfred Health, Melbourne, Australia.
authors: Peter
authors: P
authors: Cameron
authors: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia Calembeena Consulting, Melbourne, Australia.
authors: Louise
authors: L
authors: Phillips
mesh_terms: D000328:Adult; D000368:Aged; D001315:Australia / Q000453:epidemiology; D018572:Disease-Free Survival; D005169:Factor VIII / Q000008:administration & dosage* / Q000009:adverse effects; D015944:Factor VIIIa / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009520:New Zealand / Q000453:epidemiology; D012042:Registries; D015996:Survival Rate
chemical_list: D015944:Factor VIIIa; C078147:F8 protein, human; D005169:Factor VIII