
<ArticleTitle>Anti-<prot>tissue factor pathway inhibitor</prot> activity in patients with primary antiphospholipid syndrome.</ArticleTitle>
<AbstractText>The association between antiphospholipid antibodies and an increased risk of thrombosis in antiphospholipid syndrome (aPS) patients is probably caused by numerous mechanisms, including the effects of antibodies to phospholipid-binding proteins such as <prot>beta(2)-glycoprotein I</prot> and <prot>prothrombin</prot>. In this study, we investigated the inhibition of <prot>tissue factor pathway inhibitor</prot> (<prot>TFPI</prot>) in 33 patients with primary antiphospholipid syndrome (PAPS). <prot>TFPI</prot> was measured in PAPS patients using an amidolytic assay, dependent on the generation of activated factor X (<prot>Fxa</prot>), and this was compared with 55 healthy subjects. Functional levels of <prot>TFPI</prot> (mean +/- SD) were significantly lower in PAPS patients (0.89 +/- 0.37 U/ml) than the control group (1.05 +/- 0.15 U/ml) (P = 0.02). The difference was caused by a subset of five patients who had <prot>TFPI</prot> levels below the lower 99% confidence interval of the normal reference range, representing increased <prot>FXa</prot> generation in the assay system. IgG fractions were isolated from these five patients and five control subjects, then incorporated into normal plasma to measure <prot>FXa</prot> generation in the <prot>TFPI</prot> assay system. <prot>FXa</prot> generation was increased when polyclonal rabbit anti-human <prot>TFPI</prot> IgG (P &#60; 0.0001) or PAPS IgG (P = 0.0001) were added to normal plasma, demonstrating inhibition of <prot>TFPI</prot>. The apparent anti-<prot>TFPI</prot> activity demonstrated in the five subjects with PAPS in this study may represent a significant new mechanism for thrombosis in patients with aPS, as it implies that increased tissue factor <prot>FVIIa</prot>-mediated <prot>thrombin</prot> generation might occur.</AbstractText>
