INACTIVATION OF FACTOR XIA IN HUMAN PLASMA ASSESSED BY MEASURING FACTOR XIA-PROTEASE INHIBITOR COMPLEXES - MAJOR ROLE FOR C1-INHIBITOR

From experiments with purified proteins, it has been concluded that fa ctor XIa (FXIa) is inhibited in plasma mainly by alpha(1)-antitrypsin (a1AT), followed by antithrombin III (ATIII), C1-inhibitor (C1Inh), an d alpha(2)-antiplasmin (a2AP). However, the validity of this concept h as never been studied in plasma. We established the relative contribut ion of different inhibitors to the inactivation of FXIa in human plasm a, using enzyme-linked immunosorbent assays (ELISAs) for the quantific ation 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% w ith a2AP, 23.5% with a1AT, and 5% with ATIII. The distribution of FXIa between these inhibitors in plasma was independent of whether FXIa wa s added to plasma, or was activated endogenously by kaolin, celite, or glass. However, in the presence of heparin (1 or 50 U/mL), C1Inh appe ared to be the major inhibitor of FXIa, followed by ATIII. Furthermore , at lower temperatures, less FXIa-C1Inh and FXIa-a1AT complexes but m ore FXIa-a2AP complexes were formed. These data demonstrate that the c ontribution of the different inhibitors to inactivation of FXIa in pla sma may vary, but C1Inh is the principal inhibitor under most conditio ns. (C) 1995 by The American Society of Hematology.