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Anti-tissue factor pathway inhibitor activity in patients with primary antiphospholipid syndrome
Journal article   Peer reviewed

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

M.J. Adams, S. Donohoe, I.J. Mackie and S.J. Machin
British Journal of Haematology, Vol.114(2), pp.375-379
2001
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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 β2‐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 ± 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 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 < 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.

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Collaboration types
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.75 Blood Clotting
1.75.326 Antiphospholipid Syndrome
Web Of Science research areas
Hematology
ESI research areas
Clinical Medicine
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