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<title>UTas ePrints - The effects of tissue factor pathway inhibitor and anti-beta-2-glycoprotein-I IgG on thrombin generation</title>
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<meta content="Lean, Sim Yee" name="eprints.creators_name" />
<meta content="Ellery, Paul E.W." name="eprints.creators_name" />
<meta content="Ivey, Leesa" name="eprints.creators_name" />
<meta content="Thom, J." name="eprints.creators_name" />
<meta content="Oostryck, R." name="eprints.creators_name" />
<meta content="Leahy, Michael" name="eprints.creators_name" />
<meta content="Baker, Ross I." name="eprints.creators_name" />
<meta content="Adams, M.J." name="eprints.creators_name" />
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<meta content="Murray.Adams@utas.edu.au" name="eprints.creators_id" />
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<meta content="2007-09-27" name="eprints.datestamp" />
<meta content="2008-01-08 15:30:00" name="eprints.lastmod" />
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<meta content="The effects of tissue factor pathway inhibitor and anti-beta-2-glycoprotein-I IgG on thrombin generation" name="eprints.title" />
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<meta content="antiphospholipid antibodies, tissue factor pathway inhibitor, thrombin
generation, b-2-glycoprotein-I." name="eprints.keywords" />
<meta content="BACKGROUND AND OBJECTIVES: Recent evidence suggests that autoantibodies to tissue factor pathway inhibitor (TFPI) and/or antiphospholipid antibodies (aPL) may contribute to upregulation of the tissue factor (TF) pathway of blood coagulation and the development of thrombotic complications in the antiphospholipid syndrome (aPS). The aim of this study was to determine the influence of aPL e.g. anti-beta-2-glycoprotein-I (anti-beta2GPI) and anti-prothrombin, on in vitro TF-induced thrombin generation in the presence and absence of TFPI.
DESIGN-AND-METHODS: IgG fractions were collected from subjects with aPL (n=21) and normal controls (n=36). Anti-TFPI activity was determined after incubation of IgG isolated from control or subject plasma with pooled normal plasma using an amidolytic assay for TFPI. The influence of IgG fractions and purified aPL (anti-beta2GPI and anti-prothrombin) on TF-induced in vitro thrombin generation was determined using a chromogenic assay of thrombin activity. RESULTS: Patients with aPL had significantly elevated thrombin generation (median [interquartile range]) compared to normal controls (112.0 [104.0-124.0]% vs 89.9 [85.7-100.9]%, respectively; p<0.001). Thrombin generation was significantly correlated with anti-TFPI activity in patients with aPL (r(s)=0.452; p=0.039). It was also demonstrated that anti-beta2GPI, but not anti-prothrombin IgG antibodies, significantly enhanced TF-induced thrombin generation in the presence of TFPI, using both purified and patients' samples.
INTERPRETATION-AND-CONCLUSIONS: Our findings support the hypothesis that anti-beta2GPI IgG antibodies accelerate thrombin generation in the presence of TFPI and may contribute to hypercoagulability in patients with aPS." name="eprints.abstract" />
<meta content="2006-10" name="eprints.date" />
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<meta content="Haematologica" name="eprints.publication" />
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<meta content="10" name="eprints.number" />
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<meta content="0390-6078" name="eprints.issn" />
<meta content="1. Wilson WA, Gharavi AE, Koike T,
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335-46." name="eprints.referencetext" />
<meta content="Lean, Sim Yee and Ellery, Paul E.W. and Ivey, Leesa and Thom, J. and Oostryck, R. and Leahy, Michael and Baker, Ross I. and Adams, M.J. (2006) The effects of tissue factor pathway inhibitor and anti-beta-2-glycoprotein-I IgG on thrombin generation. Haematologica, 91 (10). pp. 1360-1366. ISSN 0390-6078" name="eprints.citation" />
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<meta content="Ellery, Paul E.W." name="DC.creator" />
<meta content="Ivey, Leesa" name="DC.creator" />
<meta content="Thom, J." name="DC.creator" />
<meta content="Oostryck, R." name="DC.creator" />
<meta content="Leahy, Michael" name="DC.creator" />
<meta content="Baker, Ross I." name="DC.creator" />
<meta content="Adams, M.J." name="DC.creator" />
<meta content="321008 Haematology" name="DC.subject" />
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<meta content="BACKGROUND AND OBJECTIVES: Recent evidence suggests that autoantibodies to tissue factor pathway inhibitor (TFPI) and/or antiphospholipid antibodies (aPL) may contribute to upregulation of the tissue factor (TF) pathway of blood coagulation and the development of thrombotic complications in the antiphospholipid syndrome (aPS). The aim of this study was to determine the influence of aPL e.g. anti-beta-2-glycoprotein-I (anti-beta2GPI) and anti-prothrombin, on in vitro TF-induced thrombin generation in the presence and absence of TFPI.
DESIGN-AND-METHODS: IgG fractions were collected from subjects with aPL (n=21) and normal controls (n=36). Anti-TFPI activity was determined after incubation of IgG isolated from control or subject plasma with pooled normal plasma using an amidolytic assay for TFPI. The influence of IgG fractions and purified aPL (anti-beta2GPI and anti-prothrombin) on TF-induced in vitro thrombin generation was determined using a chromogenic assay of thrombin activity. RESULTS: Patients with aPL had significantly elevated thrombin generation (median [interquartile range]) compared to normal controls (112.0 [104.0-124.0]% vs 89.9 [85.7-100.9]%, respectively; p<0.001). Thrombin generation was significantly correlated with anti-TFPI activity in patients with aPL (r(s)=0.452; p=0.039). It was also demonstrated that anti-beta2GPI, but not anti-prothrombin IgG antibodies, significantly enhanced TF-induced thrombin generation in the presence of TFPI, using both purified and patients' samples.
INTERPRETATION-AND-CONCLUSIONS: Our findings support the hypothesis that anti-beta2GPI IgG antibodies accelerate thrombin generation in the presence of TFPI and may contribute to hypercoagulability in patients with aPS." name="DC.description" />
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<h1 class="ep_tm_pagetitle">The effects of tissue factor pathway inhibitor and anti-beta-2-glycoprotein-I IgG on thrombin generation</h1>
<p style="margin-bottom: 1em" class="not_ep_block"><span class="person_name">Lean, Sim Yee</span> and <span class="person_name">Ellery, Paul E.W.</span> and <span class="person_name">Ivey, Leesa</span> and <span class="person_name">Thom, J.</span> and <span class="person_name">Oostryck, R.</span> and <span class="person_name">Leahy, Michael</span> and <span class="person_name">Baker, Ross I.</span> and <span class="person_name">Adams, M.J.</span> (2006) <xhtml:em>The effects of tissue factor pathway inhibitor and anti-beta-2-glycoprotein-I IgG on thrombin generation.</xhtml:em> Haematologica, 91 (10). pp. 1360-1366. ISSN 0390-6078</p><p style="margin-bottom: 1em" class="not_ep_block"></p><table style="margin-bottom: 1em" class="not_ep_block"><tr><td valign="top" style="text-align:center"><a href="http://eprints.utas.edu.au/843/1/Lean_et_al_2006.pdf"><img alt="[img]" src="http://eprints.utas.edu.au/style/images/fileicons/application_pdf.png" class="ep_doc_icon" border="0" /></a></td><td valign="top"><a href="http://eprints.utas.edu.au/843/1/Lean_et_al_2006.pdf"><span class="ep_document_citation">PDF</span></a> - Full text restricted - Requires a PDF viewer<br />139Kb</td></tr></table><div class="not_ep_block"><h2>Abstract</h2><p style="padding-bottom: 16px; text-align: left; margin: 1em auto 0em auto">BACKGROUND AND OBJECTIVES: Recent evidence suggests that autoantibodies to tissue factor pathway inhibitor (TFPI) and/or antiphospholipid antibodies (aPL) may contribute to upregulation of the tissue factor (TF) pathway of blood coagulation and the development of thrombotic complications in the antiphospholipid syndrome (aPS). The aim of this study was to determine the influence of aPL e.g. anti-beta-2-glycoprotein-I (anti-beta2GPI) and anti-prothrombin, on in vitro TF-induced thrombin generation in the presence and absence of TFPI.
DESIGN-AND-METHODS: IgG fractions were collected from subjects with aPL (n=21) and normal controls (n=36). Anti-TFPI activity was determined after incubation of IgG isolated from control or subject plasma with pooled normal plasma using an amidolytic assay for TFPI. The influence of IgG fractions and purified aPL (anti-beta2GPI and anti-prothrombin) on TF-induced in vitro thrombin generation was determined using a chromogenic assay of thrombin activity. RESULTS: Patients with aPL had significantly elevated thrombin generation (median [interquartile range]) compared to normal controls (112.0 [104.0-124.0]% vs 89.9 [85.7-100.9]%, respectively; p<0.001). Thrombin generation was significantly correlated with anti-TFPI activity in patients with aPL (r(s)=0.452; p=0.039). It was also demonstrated that anti-beta2GPI, but not anti-prothrombin IgG antibodies, significantly enhanced TF-induced thrombin generation in the presence of TFPI, using both purified and patients' samples.
INTERPRETATION-AND-CONCLUSIONS: Our findings support the hypothesis that anti-beta2GPI IgG antibodies accelerate thrombin generation in the presence of TFPI and may contribute to hypercoagulability in patients with aPS.</p></div><table style="margin-bottom: 1em" cellpadding="3" class="not_ep_block" border="0"><tr><th valign="top" class="ep_row">Item Type:</th><td valign="top" class="ep_row">Article</td></tr><tr><th valign="top" class="ep_row">Keywords:</th><td valign="top" class="ep_row">antiphospholipid antibodies, tissue factor pathway inhibitor, thrombin
generation, b-2-glycoprotein-I.</td></tr><tr><th valign="top" class="ep_row">Subjects:</th><td valign="top" class="ep_row"><a href="http://eprints.utas.edu.au/view/subjects/321008.html">320000 Medical and Health Sciences > 321000 Clinical Sciences > 321008 Haematology</a><br /><a href="http://eprints.utas.edu.au/view/subjects/300504.html">300000 Agricultural, Veterinary and Environmental Sciences > 300500 Veterinary Sciences > 300504 Immunology</a></td></tr><tr><th valign="top" class="ep_row">ID Code:</th><td valign="top" class="ep_row">843</td></tr><tr><th valign="top" class="ep_row">Deposited By:</th><td valign="top" class="ep_row"><span class="ep_name_citation"><span class="person_name">Dr Murray J Adams</span></span></td></tr><tr><th valign="top" class="ep_row">Deposited On:</th><td valign="top" class="ep_row">27 Sep 2007</td></tr><tr><th valign="top" class="ep_row">Last Modified:</th><td valign="top" class="ep_row">09 Jan 2008 02:30</td></tr><tr><th valign="top" class="ep_row">ePrint Statistics:</th><td valign="top" class="ep_row"><a target="ePrintStats" href="/es/index.php?action=show_detail_eprint;id=843;">View statistics for this ePrint</a></td></tr></table><p align="right">Repository Staff Only: <a href="http://eprints.utas.edu.au/cgi/users/home?screen=EPrint::View&eprintid=843">item control page</a></p>
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