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

Citation

Adams, MJ and Donohoe, S and Mackie, IJ and Machin, SJ, Anti-tissue factor pathway inhibitor activity in patients with primary antiphospholipid syndrome, British Journal of Haematology, 114, (2) pp. 375-379. ISSN 0007-1048 (2001) [Refereed Article]

DOI: doi:10.1046/j.1365-2141.2001.02923.x

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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Haematology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Blood Disorders
Author:Adams, MJ (Dr Murray Adams)
ID Code:43862
Year Published:2001
Web of Science® Times Cited:21
Deposited By:Health Sciences A
Deposited On:2007-10-10
Last Modified:2007-10-10
Downloads:0

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