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Inactivation of factor XIa in human plasma assessed by measuring factor
XIa-protease inhibitor complexes: major role for C1-inhibitor
WA Wuillemin, M Minnema, JC Meijers, D Roem, AJ Eerenberg, JH Nuijens, H ten Cate and CE Hack
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service,
Amsterdam.
From experiments with purified proteins, it has been concluded that factor
XIa (FXIa) is inhibited in plasma mainly by alpha 1-antitrypsin (a1AT),
followed by antithrombin III (ATIII), C1-inhibitor (C1Inh), and alpha
2-antiplasmin (a2AP). However, the validity of this concept has never been
studied in plasma. We established the relative contribution of different
inhibitors to the inactivation of FXIa in human plasma, using enzyme-linked
immunosorbent assays (ELISAs) for the quantification of complexes of FXIa
with a1AT, C1Inh, a2AP, and ATIII. We found that 47% of FXIa added to
plasma formed complexes with C1Inh, 24.5% with a2AP, 23.5% with a1AT, and
5% with ATIII. The distribution of FXIa between these inhibitors in plasma
was independent of whether FXIa was added to plasma, or was activated
endogenously by kaolin, celite, or glass. However, in the presence of
heparin (1 or 50 U/mL), C1Inh appeared to be the major inhibitor of FXIa,
followed by ATIII. Furthermore, at lower temperatures, less FXIa-C1Inh and
FXIa-a1AT complexes but more FXIa-a2AP complexes were formed. These data
demonstrate that the contribution of the different inhibitors to
inactivation of FXIa in plasma may vary, but C1Inh is the principal
inhibitor under most conditions.
Volume 85,
Issue 6,
pp. 1517-1526,
03/15/1995
Copyright © 1995 by The American Society of Hematology
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