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Anti-tissue factor pathway inhibitor activity in patients with primary antiphospholipid syndrome

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Adams, MJ and Donohoe, S and Mackie, IJ and Machin, SJ (2001) Anti-tissue factor pathway inhibitor activity in patients with primary antiphospholipid syndrome. British Journal of Haematology, 114. pp. 375-379.

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Abstract

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 b2-glycoprotein I
and prothrombin. In this study, we investigated the
inhibition of tissue factor pathway inhibitor (TFPI) in 33
patients with primary antiphospholipid syndrome (PAPS).
TFPI was measured in PAPS patients using an amidolytic
assay, dependent on the generation of activated factor X
(Fxa), and this was compared with 55 healthy subjects.
Functional levels of TFPI (mean plus or minus SD) were significantly
lower in PAPS patients (0.89 plus or minus 0.37 U/ml) than the
control group (1.05 plus or minus 0.15 U/ml) (P = 0.02). The difference
was caused by a subset of five patients who had TFPI
levels below the lower 99% confidence interval of the
normal reference range, representing increased FXa generation
in the assay system. IgG fractions were isolated from
these five patients and five control subjects, then incorporated
into normal plasma to measure FXa generation in the
TFPI assay system. FXa generation was increased when
polyclonal rabbit anti-human TFPI IgG (P less than 0.0001) or
PAPS IgG (P = 0.0001) were added to normal plasma,
demonstrating inhibition of TFPI. The apparent anti-TFPI
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 FVIIa-mediated thrombin generation might
occur.

Item Type: Article
Keywords: TFPI, antiphospholipid syndrome, anti-TFPI activity, factor Xa, thrombosis.
Journal or Publication Title: British Journal of Haematology
Page Range: pp. 375-379
Identification Number - DOI: 10.1046/j.1365-2141.2001.02923.x
Additional Information:

The definitive version is available at www.blackwell-synergy.com

Date Deposited: 10 Sep 2007
Last Modified: 18 Nov 2014 03:21
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