title: Clearance of human factor XIa-inhibitor complexes in rats.
abstract: The serpins C1 esterase inhibitor (C1Inh), antithrombin (AT), alpha 1-antitrypsin (alpha 1AT) and alpha 2-antiplasmin (alpha 2AP) are known inhibitors of coagulation factor XIa (FXIa). Although initial studies suggested alpha 1AT 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 (t1/2) was 98 min for FXIa-alpha 1AT complexes, whereas it was considerably shorter, i.e. 19, 18 and 15 min for FXIa-C1Inh, FXIa-alpha 2AP and FXIa-AT complexes, respectively. Thus, due to this different plasma t1/2, preferentially FXIa-alpha 1AT 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.
authors.affiliation: Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands.
authors.forename: W A
authors.initials: WA
authors.lastname: Wuillemin
authors.forename: W K
authors.initials: WK
authors.lastname: Bleeker
authors.forename: J
authors.initials: J
authors.lastname: Agterberg
authors.forename: G
authors.initials: G
authors.lastname: Rigter
authors.forename: H
authors.initials: H
authors.lastname: ten Cate
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology*; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D015945:Factor XIa / Q000378:metabolism* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D008954:Models, Biological; D051381:Rats; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*; D000979:alpha-2-Antiplasmin / Q000494:pharmacology*
chemical_list: D003174:Complement C1 Inactivator Proteins; D000515:alpha 1-Antitrypsin; D000979:alpha-2-Antiplasmin; D000990:Antithrombin III; D015945:Factor XIa