High titers of autoantibodies to tissue factor pathway inhibitor are associated with the antiphospholipid syndrome

Abstract

Summary: As the activity of the tissue factor pathway inhibitor (TFPI) may be impaired in patients with antiphospholipid antibodies (aPL), 162 aPL patients were evaluated for auto-antibodies to recombinant TFPI (anti-TFPI) using an optimized ELISA. Anti-TFPI (>18UmL -1 for IgG and/or> 15 U mL -1 for IgM) were detected in 54 patients with aPL (33.3%) and in three out of 79 normal controls (3.8%, P < 0.0001). Among aPL patients, the prevalence of positive anti-TFPI was 38.3 and 28.4% in those with or without diagnosis of definite antiphospholipid syndrome (APS). Patients with definite APS had a significantly greater frequency of high titer (>50UmL -1) anti-TFPI than aPL patients from the no definite APS group (18.5% vs. 6.2%, OR 3.7, P = 0.017). Most aPL recognized full-length TFPI, but not a truncated form of TFPI lacking the C-terminus of the molecule. Isolated IgGs from subjects with anti-TFPI impaired the dose-dependent inhibitory effect of TFPI on factor Xa activity in the presence, but not in the absence of phospho-lipid vesicles. Thus, aPL with high titer anti-TFPI limit TFPI action and are associated with the APS. © 2003 International Society on Thrombosis and Haemostasis.