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Anti-tissue factor pathway inhibitor activity in subjects with antiphospholipid syndrome is associated with increased thrombin generation

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Adams, MJ, Breckler, L, Stevens, P, Thom, J, Baker, RI and Oostryck, R 2004 , 'Anti-tissue factor pathway inhibitor activity in subjects with antiphospholipid syndrome is associated with increased thrombin generation' , Haematologica, vol. 89, no. 8 , pp. 895-990 .

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Abstract

Background and Objectives. Immunoglobulin G (IgG) fractions from subjects with
antiphospholipid syndrome (aPS) have previously been demonstrated to have inhibitory
activity against tissue factor pathway inhibitor (TFPI). This may contribute to the development
of a prothrombotic state by impaired regulation of the tissue factor (TF) pathway.
This study investigated the effect that IgG fractions from aPS subjects containing
anti-TFPI activity have on in vitro TF-induced thrombin generation.
Design and Methods. TFPI and anti-TFPI activities were determined in normal controls
(n=29) and aPS subjects (n=57). TFPI activity was determined using an amidolytic assay
based on the generation of factor Xa. Anti-TFPI activity was determined after incubating
IgG isolated from a control or subject plasma with pooled normal plasma, using the TFPI
activity assay. The influence of IgG fractions from controls (n=10) and subjects (n=23)
on TF-induced in vitro thrombin generation was determined using a chromogenic assay
of thrombin activity.
Results. TFPI activity in controls (1.13 +/- 0.25 U/mL) was significantly lower than in subjects
(1.30 +/- 0.42 U/mL) (p < 0.05). Anti-TFPI activity was significantly higher in subjects
than controls (p = 0.0001). TF-induced thrombin generation was positively associated
with anti-TFPI activity (r = 0.356; p > 0.05), with increased levels of each demonstrated
in 5 subjects.
Interpretations and Conclusions. Anti-TFPI activity was confirmed in 65% of aPS subjects.
IgG fractions demonstrated a variable ability to interfere with TFPI function and TFinduced
thrombin generation. Cross-reacting antiphospholipid antibodies and/or other
entities may interfere with TFPI function, resulting in a net increase in thrombin generation
and an increased thrombotic risk.

Item Type: Article
Authors/Creators:Adams, MJ and Breckler, L and Stevens, P and Thom, J and Baker, RI and Oostryck, R
Keywords: antiphospholipid syndrome, TFPI, thrombosis, anti-TFPI activity
Journal or Publication Title: Haematologica
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