CLEARANCE OF HUMAN FACTOR XIA-INHIBITOR COMPLEXES IN RATS

The serpins C1 esterase inhibitor (C1Inh), antithrombin (AT), alpha(1) -antitrypsin (alpha 1AT) and alpha(2)-antiplasmin (alpha 2AP) are know n inhibitors of coagulation factor XIa (FXIa). Although initial studie s suggested alpha 1AT to be the main inhibitor of FXIa, we recently de monstrated C1Inh to be a predominant inhibitor of FXIa in vitro in hum an plasma. The present study was performed to investigate the plasma e limination kinetics of preformed human FXIa-FXIa inhibitor complexes i njected in rats. The amounts of complexes remaining in circulation wer e measured using enzyme-linked immunosorbent assays. The plasma half-l ife time of clearance (t(1/2)) was 98 min far FXIa-alpha 1AT complexes , whereas it was considerably shorter, i.e. 19, 18 and 15 min far FXIa -C1Inh, FXIa-alpha 2AP and FXIa-AT complexes. respectively. Thus, due to this different plasma t(1/2), preferentially FXIa-alpha 1AT complex es may be detected in clinical samples. Furthermore. measuring FXIa-FX Ia inhibitor complexes in patient samples may not help to clarify tile relative contribution of the individual serpins to inactivation of FX Ia in vivo.