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Clearance of human factor XIa–inhibitor complexes in rats
Author(s) -
Wuillemin Walter A.,
Bleeker Wim K.,
Agterb erg Jacques,
Rigter Gemma,
Cate Hugoten,
Hack C.Erik
Publication year - 1996
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.1365-2141.1996.d01-1740.x
Subject(s) - antithrombin , chemistry , in vivo , alpha (finance) , enzyme inhibitor , human plasma , recombinant dna , in vitro , biochemistry , pharmacology , chromatography , biology , heparin , medicine , construct validity , microbiology and biotechnology , nursing , gene , patient satisfaction
The serpins C1 esterase inhibitor (C1Inh), antithrombin (AT), α 1 ‐antitrypsin (α1AT) and α 2 ‐antiplasmin (α2AP) are known inhibitors of coagulation factor XIa (FXIa). Although initial studies suggested α1AT to be the main inhibitor of FXIa, we recently demonstrated C1Inh to be a predominant inhibitor of FXIa in vitro in human plasma. The present study was performed to investigate the plasma elimination kinetics of preformed human FXIa–FXIa inhibitor complexes injected in rats. The amounts of complexes remaining in circulation were measured using enzyme‐linked immunosorbent assays. The plasma half‐life time of clearance ( t 1/2 ) was 98 min for FXIa–α1AT complexes, whereas it was considerably shorter, i.e. 19, 18 and 15 min for FXIa–C1Inh, FXIa–α2AP and FXIa–AT complexes, respectively. Thus, due to this different plasma t 1/2 , preferentially FXIa–α1AT complexes may be detected in clinical samples. Furthermore, measuring FXIa–FXIa inhibitor complexes in patient samples may not help to clarify the relative contribution of the individual serpins to inactivation of FXIa in vivo