['Tissue factor pathway inhibitor (TFPI) is a multidomain protein that negatively regulates the coagulation cascade. TFPI inhibits the tissue factor (TF)-activated factor\xa0VII-activated FX (FXa) complex during TF-mediated coagulation initiation. The aptamer BAX\xa0499 binds specifically to TFPI and inhibits its function, mediating a procoagulant effect in both in\xa0vitro and in\xa0vivo models of hemophilia.', 'This study sought to identify the regions of TFPI that are critical for BAX\xa0499 binding, and to determine how binding mediates aptamer inhibition of TFPI.', 'In\xa0vitro biochemical methods were used to evaluate the BAX\xa0499 interaction with and inhibition of TFPI. Binding experiments indicated that the full-length TFPI protein is required for tight aptamer binding. Binding-competition experiments implicated the Kunitz\xa01, Kunitz\xa03 and C-terminal domains of TFPI in aptamer binding, a finding that is supported by hydrogen-deuterium exchange experiments, and indicated that aptamer and FXa can bind simultaneously to TFPI. In enzymatic assays, BAX\xa0499 inhibited TFPI in a manner that is distinct from domain-specific antibodies, and aptamer inhibitory activity is reduced in the presence of the TFPI cofactor protein\xa0S.'] Does aptamer BAX 499 mediate inhibition of tissue factor pathway inhibitor via interaction with multiple domains of the protein?