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  5.     <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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  13.     <meta content="Adams, M.J." name="eprints.creators_name" />
  14. <meta content="Breckler, L." name="eprints.creators_name" />
  15. <meta content="Stevens, P." name="eprints.creators_name" />
  16. <meta content="Thom, J." name="eprints.creators_name" />
  17. <meta content="Baker, Ross I." name="eprints.creators_name" />
  18. <meta content="Oostryck, R." name="eprints.creators_name" />
  19. <meta content="article" name="eprints.type" />
  20. <meta content="2007-09-27" name="eprints.datestamp" />
  21. <meta content="2008-01-08 15:30:00" name="eprints.lastmod" />
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  23. <meta content="Anti-tissue factor pathway inhibitor activity in
  24. subjects with antiphospholipid syndrome is
  25. associated with increased thrombin generation" name="eprints.title" />
  26. <meta content="pub" name="eprints.ispublished" />
  27. <meta content="321008" name="eprints.subjects" />
  28. <meta content="restricted" name="eprints.full_text_status" />
  29. <meta content="antiphospholipid syndrome, TFPI, thrombosis, anti-TFPI activity" name="eprints.keywords" />
  30. <meta content="Background and Objectives. Immunoglobulin G (IgG) fractions from subjects with
  31. antiphospholipid syndrome (aPS) have previously been demonstrated to have inhibitory
  32. activity against tissue factor pathway inhibitor (TFPI). This may contribute to the development
  33. of a prothrombotic state by impaired regulation of the tissue factor (TF) pathway.
  34. This study investigated the effect that IgG fractions from aPS subjects containing
  35. anti-TFPI activity have on in vitro TF-induced thrombin generation.
  36. Design and Methods. TFPI and anti-TFPI activities were determined in normal controls
  37. (n=29) and aPS subjects (n=57). TFPI activity was determined using an amidolytic assay
  38. based on the generation of factor Xa. Anti-TFPI activity was determined after incubating
  39. IgG isolated from a control or subject plasma with pooled normal plasma, using the TFPI
  40. activity assay. The influence of IgG fractions from controls (n=10) and subjects (n=23)
  41. on TF-induced in vitro thrombin generation was determined using a chromogenic assay
  42. of thrombin activity.
  43. Results. TFPI activity in controls (1.13 +/- 0.25 U/mL) was significantly lower than in subjects
  44. (1.30 +/- 0.42 U/mL) (p < 0.05). Anti-TFPI activity was significantly higher in subjects
  45. than controls (p = 0.0001). TF-induced thrombin generation was positively associated
  46. with anti-TFPI activity (r = 0.356; p > 0.05), with increased levels of each demonstrated
  47. in 5 subjects.
  48. Interpretations and Conclusions. Anti-TFPI activity was confirmed in 65% of aPS subjects.
  49. IgG fractions demonstrated a variable ability to interfere with TFPI function and TFinduced
  50. thrombin generation. Cross-reacting antiphospholipid antibodies and/or other
  51. entities may interfere with TFPI function, resulting in a net increase in thrombin generation
  52. and an increased thrombotic risk." name="eprints.abstract" />
  53. <meta content="2004-08" name="eprints.date" />
  54. <meta content="published" name="eprints.date_type" />
  55. <meta content="Haematologica" name="eprints.publication" />
  56. <meta content="89" name="eprints.volume" />
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  58. <meta content="895-990" name="eprints.pagerange" />
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  61. <meta content="http://www.haematologica.org/backissues/details.php?id=37361" name="eprints.official_url" />
  62. <meta content="1. Wilson W, Gharavi A, Koike T, Lockshin
  63. M, Branch W, Piette J, et al. International
  64. consensus statement on preliminary
  65. classification criteria for definite antiphospholipid
  66. syndrome: report of an
  67. international workshop. Arthritis Rheum
  68. 1999;42:1309-11.
  69. 2. Roubey RAS. Immunology of the antiphospholipid
  70. syndrome: antibodies, antigens
  71. and autoimmune response. Thromb
  72. Haemost 1999;82:656-61.
  73. 3. Martinuzzo ME, Maclouf J, Carreras LO,
  74. Levy-Toledano S. Antiphospholipid antibodies
  75. enhance thrombin-induced
  76. platelet activation and thromboxane formation.
  77. Thromb Haemost 1993;70:667-
  78. 71.
  79. 4. Shi W, Chong BH, Hogg PJ, Chesterman
  80. CN. Anticardiolipin antibodies block the
  81. inhibiton by b2-glycoprotein I of the factor
  82. Xa generating activity of platelets.
  83. Thromb Haemost 1993;70:342-5.
  84. 5. Cariou R, Tobelem G, Bellucci S, Soria J,
  85. Sora C, Maclouf J, et al. Effect of lupus
  86. anticoagulant on antithrombogenic
  87. properties of endothelia cells - inhibition
  88. of thrombomodulin-dependent protein C
  89. activation. Thromb Haemost 1988;60:
  90. 54-8.
  91. 6. Oosting JD, Derksen RHWM, Bobbink
  92. IWG, Hackeng TM, Bouma BN et al. Antiphospholipid
  93. antibodies directed against
  94. a combination of phospholipids with prothrombin,
  95. protein C or protein S: an
  96. explanation for their pathogenic mechanism.
  97. Blood 1993;81:2618-25.
  98. 7. Keeling DM, Campbell SJ, Mackie IJ,
  99. Machin SJ, Isenberg DA. The fibrinolytic
  100. response to venous occlusion and the
  101. natural anticoagulant in patients with
  102. antiphospholipid antibodies both with
  103. and without systemic lupus erythematosus.
  104. Br J Haematol 1991;77:354-9.
  105. 8. Amengual O, Atsumi T, Munther A, Kahamashta
  106. MA, Hughes GRV. The role of the
  107. tissue factor pathway in the hypercoagulable
  108. state in patients with the antiphospholipid
  109. syndrome. Thromb Haemost
  110. 1998;79:276-81.
  111. 9. Adams MJ, Donohoe S, Mackie IJ, Machin
  112. SJ. Anti-tissue factor pathway inhibitor
  113. activity in patients with primary antiphospholipid
  114. syndrome. Br J Haematol
  115. 2001;114:375-9.
  116. 10. Cakir B, Arnett FC, Roubey RAS. Autoantibodies
  117. to tissue factor pathway
  118. inhibitor (TFPI) are associated with arterial
  119. thrombosis/stroke. J Autoimmun
  120. 2000;15;OC25[abstract].
  121. 11. Forastiero RR, Martinuzzo ME, Broze GJ.
  122. High titers of autoantibodies to tissue
  123. factor pathway inhibitor are associated
  124. with the antiphospholipid syndrome. J
  125. Thromb Haemost 2003;1:718-24.
  126. 12. Sandset PM, Larsen ML, Abildgaard U,
  127. Lindahl AK, Odegaard OR. Chromogenic
  128. substrate assay of extrinsic pathway
  129. inhibitor (EPI): levels in the normal population
  130. and relation to cholesterol. Blood
  131. Coagul Fibrinol 1991;2:425-33.
  132. 13. Sheng Y, Hanly JG, Reddel SW, Kouts S,
  133. Guerin J, Koike T, et al. Detection of antiphospholipid
  134. antibodies: a single chromogenic
  135. substrate of thrombin generation
  136. sensitively detects lupus anticoagulants,
  137. anticardiolipin antibodies, plus
  138. antibodies binding b2-glycoprotein I and
  139. prothrombin. Clin Exp Immunol 2001;
  140. 12:4502-8.
  141. 14. Adams MJ, Dunstan RA, Oostryck R.
  142. Interference by lupus anticoagulant in a
  143. functional assay for tissue factor pathway
  144. inhibitor. Thromb Res 1995;80:435-
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  146. 15. Adams MJ, Oostryck R. Further investigations
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  148. in a functional assay for tissue factor
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  152. IC, Calguneri M, Celik I, et al. Clinical
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  156. state. Lupus 1999;8:737-41.
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  158. Shimura M, Hiyoyama K, et al. Aberrations
  159. of the tissue factor pathway in
  160. patients positive for lupus anticoagulant.
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  162. 1999;5:10-5.
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  164. Y. Induction of tissue factor-like
  165. activity in monocytes by anti-cardiolipin
  166. antibodies. J Immunol 1994;153:1328-
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  168. 19. Branch DW, Rodgers GM. Induction of
  169. endothelial cell tissue factor activity by
  170. sera from patients with antiphospholipid
  171. syndrome: a possible mechanism of
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  176. 25 cases and review of the literature.
  177. Haemostasis 1985;15:252-62.
  178. 21. Triplett DA, Brandt JT, Maas RL. The laboratory
  179. heterogeneity of lupus anticoagulants.
  180. Archiv Pathol Lab Med J 1985;
  181. 109:946-51.
  182. 22. Love PE, Santoro SA. Antiphospholipid
  183. antibodies: anticardiolipin and the lupus
  184. anticoagulant in systemic lupus erythematosus
  185. (SLE) and in non-SLE disorders.
  186. Prevalence and clinical significance. Ann
  187. Intern Med 1990;112:682-98.
  188. 23. Lynch A, Marlar R, Murphy J, Davila G,
  189. Santo M, Rutledge J, et al. Antiphospholipid
  190. antibodies in predicting adverse
  191. pregnancy outcome: a prospective study.
  192. Ann Intern Med 1994;120:470-5.
  193. 24. Veer CV, Mann KG. Regulation of tissue
  194. factor initiated thrombin generation by
  195. the stoichiometric inhibitors tissue factor
  196. pathway inhibitor, antithrombin II and
  197. heparin cofactor II. J Biol Chem 1997;
  198. 272:4367-77.
  199. 25. Greaves M. Antiphospholipid syndrome:
  200. state of the art with emphasis on laboratory
  201. evaluation. Haemostasis 2000;30
  202. Suppl 2:16-25.
  203. 26. Salemink I, Blezer R, Willems GM, Galli
  204. M, Bevers E, Lindhout T. Antibodies to
  205. b2GPI associated with antiphospholipid
  206. syndrome suppress the inhibitory activity
  207. of tissue factor pathway inhibitor.
  208. Thromb Haemost 2000;84:653-6." name="eprints.referencetext" />
  209. <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" />
  210. <meta content="http://eprints.utas.edu.au/1777/1/Adams_et_al_2004.pdf" name="eprints.document_url" />
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  212. <meta content="Anti-tissue factor pathway inhibitor activity in
  213. subjects with antiphospholipid syndrome is
  214. associated with increased thrombin generation" name="DC.title" />
  215. <meta content="Adams, M.J." name="DC.creator" />
  216. <meta content="Breckler, L." name="DC.creator" />
  217. <meta content="Stevens, P." name="DC.creator" />
  218. <meta content="Thom, J." name="DC.creator" />
  219. <meta content="Baker, Ross I." name="DC.creator" />
  220. <meta content="Oostryck, R." name="DC.creator" />
  221. <meta content="321008 Haematology" name="DC.subject" />
  222. <meta content="Background and Objectives. Immunoglobulin G (IgG) fractions from subjects with
  223. antiphospholipid syndrome (aPS) have previously been demonstrated to have inhibitory
  224. activity against tissue factor pathway inhibitor (TFPI). This may contribute to the development
  225. of a prothrombotic state by impaired regulation of the tissue factor (TF) pathway.
  226. This study investigated the effect that IgG fractions from aPS subjects containing
  227. anti-TFPI activity have on in vitro TF-induced thrombin generation.
  228. Design and Methods. TFPI and anti-TFPI activities were determined in normal controls
  229. (n=29) and aPS subjects (n=57). TFPI activity was determined using an amidolytic assay
  230. based on the generation of factor Xa. Anti-TFPI activity was determined after incubating
  231. IgG isolated from a control or subject plasma with pooled normal plasma, using the TFPI
  232. activity assay. The influence of IgG fractions from controls (n=10) and subjects (n=23)
  233. on TF-induced in vitro thrombin generation was determined using a chromogenic assay
  234. of thrombin activity.
  235. Results. TFPI activity in controls (1.13 +/- 0.25 U/mL) was significantly lower than in subjects
  236. (1.30 +/- 0.42 U/mL) (p < 0.05). Anti-TFPI activity was significantly higher in subjects
  237. than controls (p = 0.0001). TF-induced thrombin generation was positively associated
  238. with anti-TFPI activity (r = 0.356; p > 0.05), with increased levels of each demonstrated
  239. in 5 subjects.
  240. Interpretations and Conclusions. Anti-TFPI activity was confirmed in 65% of aPS subjects.
  241. IgG fractions demonstrated a variable ability to interfere with TFPI function and TFinduced
  242. thrombin generation. Cross-reacting antiphospholipid antibodies and/or other
  243. entities may interfere with TFPI function, resulting in a net increase in thrombin generation
  244. and an increased thrombotic risk." name="DC.description" />
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  358.     <h1 class="ep_tm_pagetitle">Anti-tissue factor pathway inhibitor activity in subjects with antiphospholipid syndrome is associated with increased thrombin generation</h1>
  359.     <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&#13;
  360. antiphospholipid syndrome (aPS) have previously been demonstrated to have inhibitory&#13;
  361. activity against tissue factor pathway inhibitor (TFPI). This may contribute to the development&#13;
  362. of a prothrombotic state by impaired regulation of the tissue factor (TF) pathway.&#13;
  363. This study investigated the effect that IgG fractions from aPS subjects containing&#13;
  364. anti-TFPI activity have on in vitro TF-induced thrombin generation.&#13;
  365. Design and Methods. TFPI and anti-TFPI activities were determined in normal controls&#13;
  366. (n=29) and aPS subjects (n=57). TFPI activity was determined using an amidolytic assay&#13;
  367. based on the generation of factor Xa. Anti-TFPI activity was determined after incubating&#13;
  368. IgG isolated from a control or subject plasma with pooled normal plasma, using the TFPI&#13;
  369. activity assay. The influence of IgG fractions from controls (n=10) and subjects (n=23)&#13;
  370. on TF-induced in vitro thrombin generation was determined using a chromogenic assay&#13;
  371. of thrombin activity.&#13;
  372. Results. TFPI activity in controls (1.13 +/- 0.25 U/mL) was significantly lower than in subjects&#13;
  373. (1.30 +/- 0.42 U/mL) (p &lt; 0.05). Anti-TFPI activity was significantly higher in subjects&#13;
  374. than controls (p = 0.0001). TF-induced thrombin generation was positively associated&#13;
  375. with anti-TFPI activity (r = 0.356; p &gt; 0.05), with increased levels of each demonstrated&#13;
  376. in 5 subjects.&#13;
  377. Interpretations and Conclusions. Anti-TFPI activity was confirmed in 65% of aPS subjects.&#13;
  378. IgG fractions demonstrated a variable ability to interfere with TFPI function and TFinduced&#13;
  379. thrombin generation. Cross-reacting antiphospholipid antibodies and/or other&#13;
  380. entities may interfere with TFPI function, resulting in a net increase in thrombin generation&#13;
  381. 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 &gt; 321000 Clinical Sciences &gt; 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&amp;eprintid=1777">item control page</a></p>
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