Logo image
Anti-tissue factor pathway inhibitor activity in subjects with antiphospholipid syndrome is associated with increased thrombin generation
Journal article   Open access   Peer reviewed

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

M. Adams, L. Breckler, P. Stevens, J. Thom, R. Baker and R. Oostryck
Haematologica, Vol.89(8), pp.985-990
2004
pdf
Anti-tissue factor pathway inhibitor activity in subjects with antiphospholipid syndrome is associated with increased thrombin generation.pdfDownloadView
Published (Version of Record) Open Access
url
Free to Read *No subscription requiredView

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. INTERPRETATION AND CONCLUSIONS: Anti-TFPI activity was confirmed in 65% of aPS subjects. IgG fractions demonstrated a variable ability to interfere with TFPI function and TF-induced 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.

Details

Metrics

40 File views/ downloads
38 Record Views
Logo image