title: In vitro comparison of the effect of two factor XI (FXI) concentrates on thrombin generation in major FXI deficiency.
abstract: BACKGROUND
  Bleeding risk in factor XI (FXI) deficiency following surgery may be reduced by treatment with either of two FXI concentrates, but indications for their use are unclear and treatment has been associated with thrombosis.
  
  
  OBJECTIVE
  To quantify and compare the effects of two different FXI concentrates on thrombin generation (TG) in major FXI deficiency (FXI:C < 15 IU dL(-1) ).
  
  
  METHODS
  Thrombin generation was measured in controls (n = 50), FXI-deficient individuals pre and post in vitro spiking with FXI concentrates (n = 10), and in ex vivo samples following treatment with FXI concentrate (n = 3).
  
  
  RESULTS
  Thrombin generation was significantly impaired in FXI deficiency but improved following FXI replacement in vitro and in vivo. LFB Hemoleven(®) had greater effect on TG than BPL FXI concentrate in vitro (equivalent in vivo doses 10, 20 and 30 U kg(-1) ): higher endogenous thrombin potential (ETP) (P < 0.0001), peak height (P < 0.01) velocity (P < 0.0002) and shorter lag time and time to peak (both P < 0.003). Some measurements with LFB Hemoleven(®) exceeded the reference range. At lower dose (5 U kg(-1) ), BPL FXI concentrate normalized all TG parameters and LFB Hemoleven(®) normalized the ETP but exceeded the reference range with other parameters.
  
  
  CONCLUSIONS
  Both FXI concentrates improve TG in vitro in major FXI deficiency but differ in dose response, and for both products, doses lower than previously recommended normalized TG in vitro. Comparison of in vitro spiked and ex vivo samples suggest that in vitro results could be used to estimate an expected in vivo response to FXI replacement.
authors.affiliation: Department of Haematology, Manchester Royal Infirmary, Central Manchester University Hospital NHS Trust, Manchester, UK.|Institute of Cancer Sciences, The University of Manchester, Manchester, UK.
authors.forename: G N
authors.initials: GN
authors.lastname: Pike
authors.affiliation: Haematology Molecular Diagnostics Centre, Manchester Royal Infirmary, Central Manchester University Hospital NHS Trust, Manchester, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Cumming
authors.affiliation: Department of Haematology, Manchester Royal Infirmary, Central Manchester University Hospital NHS Trust, Manchester, UK.|The University of Manchester, Manchester, UK.
authors.forename: C R M
authors.initials: CR
authors.lastname: Hay
authors.affiliation: Haematology Molecular Diagnostics Centre, Manchester Royal Infirmary, Central Manchester University Hospital NHS Trust, Manchester, UK.
authors.forename: B
authors.initials: B
authors.lastname: Sempasa
authors.affiliation: Haematology Molecular Diagnostics Centre, Manchester Royal Infirmary, Central Manchester University Hospital NHS Trust, Manchester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Sutherland
authors.affiliation: Department of Haematology, Manchester Royal Infirmary, Central Manchester University Hospital NHS Trust, Manchester, UK.
authors.forename: J
authors.initials: J
authors.lastname: Thachil
authors.affiliation: Department of Haematology, Manchester Royal Infirmary, Central Manchester University Hospital NHS Trust, Manchester, UK.|Institute of Cancer Sciences, The University of Manchester, Manchester, UK.
authors.forename: J
authors.initials: J
authors.lastname: Burthem
authors.affiliation: The University of Manchester, Manchester, UK.|SHOT office, Manchester Blood Centre, Plymouth Grove, Manchester, UK.
authors.forename: P H B
authors.initials: PH
authors.lastname: Bolton-Maggs
mesh_terms: D000328:Adult; D000368:Aged; D001780:Blood Coagulation Tests; D005172:Factor XI / Q000235:genetics / Q000627:therapeutic use*; D005173:Factor XI Deficiency / Q000188:drug therapy*; D005260:Female; D005838:Genotype; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D013917:Thrombin / Q000032:analysis*; D055815:Young Adult
chemical_list: D005172:Factor XI; D013917:Thrombin
keywords: bleeding disorder; blood coagulation; factor XI; factor XI deficiency; plasma-derived concentrate; thrombin generation