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<title>UTas ePrints - Anti-tissue factor pathway inhibitor activity in subjects with antiphospholipid syndrome is associated with increased thrombin generation</title>
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<meta content="Adams, M.J." name="eprints.creators_name" />
<meta content="Breckler, L." name="eprints.creators_name" />
<meta content="Stevens, P." name="eprints.creators_name" />
<meta content="Thom, J." name="eprints.creators_name" />
<meta content="Baker, Ross I." name="eprints.creators_name" />
<meta content="Oostryck, R." name="eprints.creators_name" />
<meta content="article" name="eprints.type" />
<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="Anti-tissue factor pathway inhibitor activity in
subjects with antiphospholipid syndrome is
associated with increased thrombin generation" name="eprints.title" />
<meta content="pub" name="eprints.ispublished" />
<meta content="321008" name="eprints.subjects" />
<meta content="restricted" name="eprints.full_text_status" />
<meta content="antiphospholipid syndrome, TFPI, thrombosis, anti-TFPI activity" name="eprints.keywords" />
<meta content="Background and Objectives. Immunoglobulin G (IgG) fractions from subjects with
antiphospholipid syndrome (aPS) have previously been demonstrated to have inhibitory
activity against tissue factor pathway inhibitor (TFPI). This may contribute to the development
of a prothrombotic state by impaired regulation of the tissue factor (TF) pathway.
This study investigated the effect that IgG fractions from aPS subjects containing
anti-TFPI activity have on in vitro TF-induced thrombin generation.
Design and Methods. TFPI and anti-TFPI activities were determined in normal controls
(n=29) and aPS subjects (n=57). TFPI activity was determined using an amidolytic assay
based on the generation of factor Xa. Anti-TFPI activity was determined after incubating
IgG isolated from a control or subject plasma with pooled normal plasma, using the TFPI
activity assay. The influence of IgG fractions from controls (n=10) and subjects (n=23)
on TF-induced in vitro thrombin generation was determined using a chromogenic assay
of thrombin activity.
Results. TFPI activity in controls (1.13 +/- 0.25 U/mL) was significantly lower than in subjects
(1.30 +/- 0.42 U/mL) (p < 0.05). Anti-TFPI activity was significantly higher in subjects
than controls (p = 0.0001). TF-induced thrombin generation was positively associated
with anti-TFPI activity (r = 0.356; p > 0.05), with increased levels of each demonstrated
in 5 subjects.
Interpretations and Conclusions. Anti-TFPI activity was confirmed in 65% of aPS subjects.
IgG fractions demonstrated a variable ability to interfere with TFPI function and TFinduced
thrombin generation. Cross-reacting antiphospholipid antibodies and/or other
entities may interfere with TFPI function, resulting in a net increase in thrombin generation
and an increased thrombotic risk." name="eprints.abstract" />
<meta content="2004-08" name="eprints.date" />
<meta content="published" name="eprints.date_type" />
<meta content="Haematologica" name="eprints.publication" />
<meta content="89" name="eprints.volume" />
<meta content="8" name="eprints.number" />
<meta content="895-990" name="eprints.pagerange" />
<meta content="UNSPECIFIED" name="eprints.thesis_type" />
<meta content="TRUE" name="eprints.refereed" />
<meta content="http://www.haematologica.org/backissues/details.php?id=37361" name="eprints.official_url" />
<meta content="1. Wilson W, Gharavi A, Koike T, Lockshin
M, Branch W, Piette J, et al. International
consensus statement on preliminary
classification criteria for definite antiphospholipid
syndrome: report of an
international workshop. Arthritis Rheum
1999;42:1309-11.
2. Roubey RAS. Immunology of the antiphospholipid
syndrome: antibodies, antigens
and autoimmune response. Thromb
Haemost 1999;82:656-61.
3. Martinuzzo ME, Maclouf J, Carreras LO,
Levy-Toledano S. Antiphospholipid antibodies
enhance thrombin-induced
platelet activation and thromboxane formation.
Thromb Haemost 1993;70:667-
71.
4. Shi W, Chong BH, Hogg PJ, Chesterman
CN. Anticardiolipin antibodies block the
inhibiton by b2-glycoprotein I of the factor
Xa generating activity of platelets.
Thromb Haemost 1993;70:342-5.
5. Cariou R, Tobelem G, Bellucci S, Soria J,
Sora C, Maclouf J, et al. Effect of lupus
anticoagulant on antithrombogenic
properties of endothelia cells - inhibition
of thrombomodulin-dependent protein C
activation. Thromb Haemost 1988;60:
54-8.
6. Oosting JD, Derksen RHWM, Bobbink
IWG, Hackeng TM, Bouma BN et al. Antiphospholipid
antibodies directed against
a combination of phospholipids with prothrombin,
protein C or protein S: an
explanation for their pathogenic mechanism.
Blood 1993;81:2618-25.
7. Keeling DM, Campbell SJ, Mackie IJ,
Machin SJ, Isenberg DA. The fibrinolytic
response to venous occlusion and the
natural anticoagulant in patients with
antiphospholipid antibodies both with
and without systemic lupus erythematosus.
Br J Haematol 1991;77:354-9.
8. Amengual O, Atsumi T, Munther A, Kahamashta
MA, Hughes GRV. The role of the
tissue factor pathway in the hypercoagulable
state in patients with the antiphospholipid
syndrome. Thromb Haemost
1998;79:276-81.
9. Adams MJ, Donohoe S, Mackie IJ, Machin
SJ. Anti-tissue factor pathway inhibitor
activity in patients with primary antiphospholipid
syndrome. Br J Haematol
2001;114:375-9.
10. Cakir B, Arnett FC, Roubey RAS. Autoantibodies
to tissue factor pathway
inhibitor (TFPI) are associated with arterial
thrombosis/stroke. J Autoimmun
2000;15;OC25[abstract].
11. Forastiero RR, Martinuzzo ME, Broze GJ.
High titers of autoantibodies to tissue
factor pathway inhibitor are associated
with the antiphospholipid syndrome. J
Thromb Haemost 2003;1:718-24.
12. Sandset PM, Larsen ML, Abildgaard U,
Lindahl AK, Odegaard OR. Chromogenic
substrate assay of extrinsic pathway
inhibitor (EPI): levels in the normal population
and relation to cholesterol. Blood
Coagul Fibrinol 1991;2:425-33.
13. Sheng Y, Hanly JG, Reddel SW, Kouts S,
Guerin J, Koike T, et al. Detection of antiphospholipid
antibodies: a single chromogenic
substrate of thrombin generation
sensitively detects lupus anticoagulants,
anticardiolipin antibodies, plus
antibodies binding b2-glycoprotein I and
prothrombin. Clin Exp Immunol 2001;
12:4502-8.
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Interference by lupus anticoagulant in a
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87:245-9.
16. Kiraz S, Ertenli L, Benekli M, Haznadaroglu
IC, Calguneri M, Celik I, et al. Clinical
significance of the hemostatic markers
and thrombomodulin in systemic
lupus erythematosus: evidence for a prothrombotic
state. Lupus 1999;8:737-41.
17. Wakita Y, Wada H, Nakase T, Nakasaki T,
Shimura M, Hiyoyama K, et al. Aberrations
of the tissue factor pathway in
patients positive for lupus anticoagulant.
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1999;5:10-5.
18. Kornberg A, Blank M, Kaufman S, Shoenfeld
Y. Induction of tissue factor-like
activity in monocytes by anti-cardiolipin
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19. Branch DW, Rodgers GM. Induction of
endothelial cell tissue factor activity by
sera from patients with antiphospholipid
syndrome: a possible mechanism of
thrombosis. Am J Obstet Gynecol 1993;
168:206-10.
20. Lechner K, Pabinger-Fasching IP. Lupus
anticoagulant and thrombosis. A study of
25 cases and review of the literature.
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21. Triplett DA, Brandt JT, Maas RL. The laboratory
heterogeneity of lupus anticoagulants.
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109:946-51.
22. Love PE, Santoro SA. Antiphospholipid
antibodies: anticardiolipin and the lupus
anticoagulant in systemic lupus erythematosus
(SLE) and in non-SLE disorders.
Prevalence and clinical significance. Ann
Intern Med 1990;112:682-98.
23. Lynch A, Marlar R, Murphy J, Davila G,
Santo M, Rutledge J, et al. Antiphospholipid
antibodies in predicting adverse
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Ann Intern Med 1994;120:470-5.
24. Veer CV, Mann KG. Regulation of tissue
factor initiated thrombin generation by
the stoichiometric inhibitors tissue factor
pathway inhibitor, antithrombin II and
heparin cofactor II. J Biol Chem 1997;
272:4367-77.
25. Greaves M. Antiphospholipid syndrome:
state of the art with emphasis on laboratory
evaluation. Haemostasis 2000;30
Suppl 2:16-25.
26. Salemink I, Blezer R, Willems GM, Galli
M, Bevers E, Lindhout T. Antibodies to
b2GPI associated with antiphospholipid
syndrome suppress the inhibitory activity
of tissue factor pathway inhibitor.
Thromb Haemost 2000;84:653-6." name="eprints.referencetext" />
<meta content="Adams, M.J. and Breckler, L. and Stevens, P. and Thom, J. and Baker, Ross I. and Oostryck, R. (2004) Anti-tissue factor pathway inhibitor activity in subjects with antiphospholipid syndrome is associated with increased thrombin generation. Haematologica, 89 (8). pp. 895-990." name="eprints.citation" />
<meta content="http://eprints.utas.edu.au/1777/1/Adams_et_al_2004.pdf" name="eprints.document_url" />
<link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" />
<meta content="Anti-tissue factor pathway inhibitor activity in
subjects with antiphospholipid syndrome is
associated with increased thrombin generation" name="DC.title" />
<meta content="Adams, M.J." name="DC.creator" />
<meta content="Breckler, L." name="DC.creator" />
<meta content="Stevens, P." name="DC.creator" />
<meta content="Thom, J." name="DC.creator" />
<meta content="Baker, Ross I." name="DC.creator" />
<meta content="Oostryck, R." name="DC.creator" />
<meta content="321008 Haematology" name="DC.subject" />
<meta content="Background and Objectives. Immunoglobulin G (IgG) fractions from subjects with
antiphospholipid syndrome (aPS) have previously been demonstrated to have inhibitory
activity against tissue factor pathway inhibitor (TFPI). This may contribute to the development
of a prothrombotic state by impaired regulation of the tissue factor (TF) pathway.
This study investigated the effect that IgG fractions from aPS subjects containing
anti-TFPI activity have on in vitro TF-induced thrombin generation.
Design and Methods. TFPI and anti-TFPI activities were determined in normal controls
(n=29) and aPS subjects (n=57). TFPI activity was determined using an amidolytic assay
based on the generation of factor Xa. Anti-TFPI activity was determined after incubating
IgG isolated from a control or subject plasma with pooled normal plasma, using the TFPI
activity assay. The influence of IgG fractions from controls (n=10) and subjects (n=23)
on TF-induced in vitro thrombin generation was determined using a chromogenic assay
of thrombin activity.
Results. TFPI activity in controls (1.13 +/- 0.25 U/mL) was significantly lower than in subjects
(1.30 +/- 0.42 U/mL) (p < 0.05). Anti-TFPI activity was significantly higher in subjects
than controls (p = 0.0001). TF-induced thrombin generation was positively associated
with anti-TFPI activity (r = 0.356; p > 0.05), with increased levels of each demonstrated
in 5 subjects.
Interpretations and Conclusions. Anti-TFPI activity was confirmed in 65% of aPS subjects.
IgG fractions demonstrated a variable ability to interfere with TFPI function and TFinduced
thrombin generation. Cross-reacting antiphospholipid antibodies and/or other
entities may interfere with TFPI function, resulting in a net increase in thrombin generation
and an increased thrombotic risk." name="DC.description" />
<meta content="2004-08" name="DC.date" />
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<meta content="Adams, M.J. and Breckler, L. and Stevens, P. and Thom, J. and Baker, Ross I. and Oostryck, R. (2004) Anti-tissue factor pathway inhibitor activity in subjects with antiphospholipid syndrome is associated with increased thrombin generation. Haematologica, 89 (8). pp. 895-990." name="DC.identifier" />
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<h1 class="ep_tm_pagetitle">Anti-tissue factor pathway inhibitor activity in subjects with antiphospholipid syndrome is associated with increased thrombin generation</h1>
<p style="margin-bottom: 1em" class="not_ep_block"><span class="person_name">Adams, M.J.</span> and <span class="person_name">Breckler, L.</span> and <span class="person_name">Stevens, P.</span> and <span class="person_name">Thom, J.</span> and <span class="person_name">Baker, Ross I.</span> and <span class="person_name">Oostryck, R.</span> (2004) <xhtml:em>Anti-tissue factor pathway inhibitor activity in subjects with antiphospholipid syndrome is associated with increased thrombin generation.</xhtml:em> Haematologica, 89 (8). pp. 895-990.</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/1777/1/Adams_et_al_2004.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/1777/1/Adams_et_al_2004.pdf"><span class="ep_document_citation">PDF</span></a> - Full text restricted - Requires a PDF viewer<br />231Kb</td></tr></table><p style="margin-bottom: 1em" class="not_ep_block">Official URL: <a href="http://www.haematologica.org/backissues/details.php?id=37361">http://www.haematologica.org/backissues/details.php?id=37361</a></p><div class="not_ep_block"><h2>Abstract</h2><p style="padding-bottom: 16px; text-align: left; margin: 1em auto 0em auto">Background and Objectives. Immunoglobulin G (IgG) fractions from subjects with
antiphospholipid syndrome (aPS) have previously been demonstrated to have inhibitory
activity against tissue factor pathway inhibitor (TFPI). This may contribute to the development
of a prothrombotic state by impaired regulation of the tissue factor (TF) pathway.
This study investigated the effect that IgG fractions from aPS subjects containing
anti-TFPI activity have on in vitro TF-induced thrombin generation.
Design and Methods. TFPI and anti-TFPI activities were determined in normal controls
(n=29) and aPS subjects (n=57). TFPI activity was determined using an amidolytic assay
based on the generation of factor Xa. Anti-TFPI activity was determined after incubating
IgG isolated from a control or subject plasma with pooled normal plasma, using the TFPI
activity assay. The influence of IgG fractions from controls (n=10) and subjects (n=23)
on TF-induced in vitro thrombin generation was determined using a chromogenic assay
of thrombin activity.
Results. TFPI activity in controls (1.13 +/- 0.25 U/mL) was significantly lower than in subjects
(1.30 +/- 0.42 U/mL) (p < 0.05). Anti-TFPI activity was significantly higher in subjects
than controls (p = 0.0001). TF-induced thrombin generation was positively associated
with anti-TFPI activity (r = 0.356; p > 0.05), with increased levels of each demonstrated
in 5 subjects.
Interpretations and Conclusions. Anti-TFPI activity was confirmed in 65% of aPS subjects.
IgG fractions demonstrated a variable ability to interfere with TFPI function and TFinduced
thrombin generation. Cross-reacting antiphospholipid antibodies and/or other
entities may interfere with TFPI function, resulting in a net increase in thrombin generation
and an increased thrombotic risk.</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 syndrome, TFPI, thrombosis, anti-TFPI activity</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></td></tr><tr><th valign="top" class="ep_row">ID Code:</th><td valign="top" class="ep_row">1777</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=1777;">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=1777">item control page</a></p>
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