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

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.

• Authors: Murray Adams, Liza Breckler, Paul Stevens, Jim Thom, Ross Baker, Robert Oostryck
• Journal: Haematologica (Haematologica) Vol. 89 Issue 8 Pg. 985-90 (Aug 2004) ISSN: 1592-8721 [Electronic] Italy
• PMID: 15339683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin G
• Lipoproteins
• lipoprotein-associated coagulation inhibitor
• Thrombin

Topics

• Adult
• Antiphospholipid Syndrome (blood, immunology)
• Female
• Humans
• Immunoglobulin G (blood)
• Lipoproteins (blood, immunology)
• Male
• Middle Aged
• Reference Values
• Thrombin (metabolism)