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Activation profiles of factor VIII in concentrates reflect one‐stage/chromogenic potency discrepancies
Author(s) -
Hubbard Anthony R.,
Weller Lynne J.,
Bevan Sally A.
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03494.x
Subject(s) - chromogenic , potency , thrombin , chemistry , von willebrand factor , coagulation , incubation , recombinant dna , von willebrand disease , incubation period , chromatography , microbiology and biotechnology , medicine , biochemistry , in vitro , platelet , biology , gene
Summary. We have investigated the possibility that differences in the profile of factor VIII (FVIII) activation, by thrombin, may help to explain the one‐stage/chromogenic potency discrepancies in two therapeutic concentrates. A Method M concentrate and a recombinant B‐domain‐deleted (B‐DD) concentrate were found to have one‐stage/chromogenic ratios of approximately 1·15 and 0·70, respectively, relative to the World Health Organization (WHO) 6th International Standard (IS) FVIII concentrate, whether pre‐diluted in FVIII‐deficient plasma or buffer (± von Willebrand factor, VWF). The activation of FVIII, by thrombin, was followed in a buffer medium (± VWF) and all three concentrates showed similar times to reach peak FVIII coagulation (FVIII:C) activity. However, despite the use of equivalent amounts of FVIII:C for all three concentrates, the B‐DD concentrate reached a higher peak level and maintained higher FVIII:C compared with the WHO 6th IS throughout the incubation period, whereas the Method M concentrate reached a lower peak level and maintained lower FVIII:C throughout the incubation period. We propose that the higher levels of FVIII:C found with the B‐DD concentrate and the lower levels with the Method M concentrate, following activation, may be reflected in the potencies obtained by the chromogenic method and may be consistent with one‐stage/chromogenic ratios of < 1·0 and > 1·0 respectively.