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In vitro comparison of the effect of two factor XI (FXI) concentrates on thrombin generation in major FXI deficiency
Author(s) -
Pike G. N.,
Cumming A. M.,
Hay C. R. M.,
Sempasa B.,
Sutherland M.,
Thachil J.,
Burthem J.,
BoltonMaggs P. H. B.
Publication year - 2016
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.12846
Subject(s) - thrombin generation , ex vivo , medicine , factor xi , in vivo , factor ix , in vitro , thrombin , platelet , chemistry , biochemistry , coagulation , biology , microbiology and biotechnology
Introduction 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. Aim 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. Conclusion 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.