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

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posted on 2023-05-25, 23:21 authored by Adams, MJ, Donohoe, S, Mackie, IJ, Machin, SJ
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.

History

Publication title

British Journal of Haematology

Volume

114

Pagination

375-379

Department/School

School of Human Life Sciences

Publication status

  • Published

Rights statement

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

Repository Status

  • Open

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