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  5.     <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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  13.     <meta content="Lean, Sim Yee" name="eprints.creators_name" />
  14. <meta content="Ellery, Paul E.W." name="eprints.creators_name" />
  15. <meta content="Ivey, Leesa" name="eprints.creators_name" />
  16. <meta content="Thom, J." name="eprints.creators_name" />
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  18. <meta content="Leahy, Michael" name="eprints.creators_name" />
  19. <meta content="Baker, Ross I." name="eprints.creators_name" />
  20. <meta content="Adams, M.J." name="eprints.creators_name" />
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  28. <meta content="Murray.Adams@utas.edu.au" name="eprints.creators_id" />
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  30. <meta content="2007-09-27" name="eprints.datestamp" />
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  33. <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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  38. <meta content="antiphospholipid antibodies, tissue factor pathway inhibitor, thrombin
  39. generation, b-2-glycoprotein-I." name="eprints.keywords" />
  40. <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. 
  41. 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. 
  42. 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" />
  43. <meta content="2006-10" name="eprints.date" />
  44. <meta content="published" name="eprints.date_type" />
  45. <meta content="Haematologica" name="eprints.publication" />
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  52. <meta content="1. Wilson WA, Gharavi AE, Koike T,
  53. Lockshin MD, Branch DW, Piette J-C,
  54. et al. International consensus statement
  55. on preliminary classification criteria for
  56. definite antiphospholipid syndrome:
  57. report of an international workshop.
  58. Arthritis Rheum 1999; 42:1309-11.
  59. 2. Roubey RAS. Immunology of the
  60. antiphospholipid antibody syndrome.
  61. Arthritis Rheum 1996; 39:1444-54.
  62. 3. Roubey RAS. Autoantibodies to phospholipid-
  63. binding plasma proteins: a
  64. new view of lupus anticoagulants and
  65. other &quot;antiphospholipid&quot; autoantibodies.
  66. Blood 1994;84:2854-67.
  67. 4. McNeil HP, Simpson RJ, Chesterman
  68. CN, Krilis SA. Anti-phospholipid antibodies
  69. are directed against a complex
  70. antigen that includes a lipid-binding
  71. inhibitor of coagulation: b2-glycoprotein
  72. I (apolipoprotein H). Proc Natl
  73. Acad Sci USA 1990;87:4120-4.
  74. 5. Galli M, Comfurius P, Maassen C,
  75. Hemker HC, de Baets MH, van Breda-
  76. Vriesman PJC, et al. Anticardiolipin
  77. antibodies (ACA) directed not to cardiolipin
  78. but to a plasma protein cofactor.
  79. Lancet 1990;335:1544-7.
  80. 6. Matsuura E, Igarashi Y, Fujimoto M,
  81. Ichikawa K, Koike T. Anticardiolipin
  82. cofactor(s) and differential diagnosis of
  83. autoimmune disease. Lancet 1990; 336:
  84. 177-8.
  85. 7. Willems GM, Janssen MP, Pelsers
  86. MMAL, Comfurius P, Galli M, Zwaal.
  87. RFA, et al. Role of divalency in the
  88. high-affinity binding of anticardiolipin
  89. antibody-b2-glycoprotein I complexes
  90. to lipid membranes. Biochemistry
  91. 1996;35:13833-13842.
  92. 8. Rao LVM, Hoang AD, Rapaport SI.
  93. Mechanism and effects of the binding
  94. of lupus anticoagulant IgG and prothrombin
  95. to surface phospholipid.
  96. Blood 1996;88:4173-82.
  97. 9. Takeya H, Mori T, Gabazza EC,
  98. Kuroda K, Deguchi H, Matsuura E, et
  99. al. Anti-b2-glycoprotein I (b2GPI) monoclonal
  100. antibodies with lupus anticoagulant-
  101. like activity enhance the b2GPI
  102. binding to phospholipids. J Clin Invest
  103. 1997;99:2260-8.
  104. 10. Broze GJ Jr, Warren LA, Novotny WF,
  105. Higuchi DA, Girard JJ, Miletich JP. The
  106. lipoprotein-associated coagulation
  107. inhibitor that inhibits the factor VII-tissue
  108. factor complex also inhibits factor
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  111. 11. Rao LVM, Rapaport SI. Studies of a
  112. mechanism inhibiting the initiation of
  113. the extrinsic pathway of coagulation.
  114. Blood 1987;69:645-51.
  115. 12. Forastiero RR, Martinuzzo ME, Broze
  116. GJ, Jr. High titers of autoantibodies to
  117. tissue factor pathway inhibitor are
  118. associated with the antiphospholipid
  119. syndrome. J Thromb Haemost 2003; 1:
  120. 718-24.
  121. 13. Adams M, Donohoe S, Mackie IJ,
  122. Machin SJ. Anti-tissue factor pathway
  123. inhibitor activity in patients with primary
  124. antiphospholipid syndrome. Br J
  125. Haematol 2001;114:357-9.
  126. 14. Adams M, Breckler L, Stevens S, Thom
  127. J, Baker R, Oostryck R. Anti-tissue factor
  128. pathway activity in subjects with
  129. antiphospholipid syndrome is associated
  130. with increased thrombin generation.
  131. Haematologica 2004;89:985-90.
  132. 15. Jacobsen EM, Sandset PM, Finn W. Do
  133. antiphospholipid antibodies interfere
  134. with tissue factor pathway inhibitor?
  135. Thrombosis Research 1999;94:213-220.
  136. 16. Salemink I, Blezer R, Willems GM,
  137. Galli M, Bevers E, Lindhout T. Antibodies
  138. to b2-glycoprotein I associated
  139. with antiphospholipid syndrome suppress
  140. the inhibitory activity of tissue
  141. factor pathway inhibitor. Thromb
  142. Haemost 2000;84:653-6.
  143. 17. Amengual O, Atsumi T, Khamashta
  144. MA, Hughes GRV. The role of the tissue
  145. factor pathway in the hypercoagulable
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  147. antiphospholipid syndrome. Thromb
  148. Haemost 1998;79:276-81.
  149. 18. Branch DW, Rodgers GM. Induction of
  150. endothelial cell tissue factor activity by
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  153. of thrombosis. Am J Obstet Gynecol
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  155. 19. Kornberg A, Blank M, Kaufman S,
  156. Shoenfeld Y. Induction of tissue factorlike
  157. activity in monocytes by anti-cardiolipin
  158. antibodies. J Immunol 1994;
  159. 153:1328-32.
  160. 20. Sheng Y, Hanly JG, Reddel SW, Kouts
  161. S, Guerin J, Koike T, et al. Detection of 'antiphospholipid' antibodies: a single
  162. chromogenic assay of thrombin generation
  163. sensitively detects lupus anticoagulants,
  164. anticardiolipin antibodies,
  165. plus antibodies binding b2-glycoprotein
  166. and prothrombin. Clin Exp Immunol
  167. 2001;124:502-8.
  168. 21. Sandset PM, Larsen ML, Abildgaard U,
  169. Lindahl AK, Odegaard OR. Chromogenic
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  179. Adamcuk Y, Broze GJ, Forastiero R.
  180. Antiphospholipid antibodies and antibodies
  181. to tissue factor pathway
  182. inhibitor in women with implantation
  183. failures or early and late pregnancy
  184. losses. J Thromb Haemost 2005;3:1-3.
  185. 24. Roubey RAS. Tissue factor pathway
  186. and the antiphospholipid syndrome. J
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  188. 25. Hanly JG, Smith SA. Anti-b(2)-glycoprotein
  189. I autoantibodies, in vitro
  190. thrombin generation, and the antiphospholipid
  191. syndrome. J Rheumatol
  192. 2000;27:2152-9.
  193. 26. Roubey RAS, Eisenberg RA, Harper
  194. MF, Winfield JB. &quot;Anticardiolipin&quot;
  195. autoantibodies recognize b2-glycoprotein
  196. I in the absence of phospholipid:
  197. importance of antigen density and
  198. bivalent binding. J Immunol 1995;
  199. 154:954-60.
  200. 27. Simmelink MJA, Horbach DA,
  201. Derksen RHWM, Meijers JCM, Bevers
  202. EM, Willems GM, et al. Complexes of
  203. anti-prothrombin antibodies and prothrombin
  204. cause lupus anticoagulant
  205. activity by competing with the binding
  206. of clotting factors for catalytic
  207. phospholipid surfaces. Br J Haematol
  208. 2001;113:621-9.
  209. 28. Matsuura E, Igarashi Y, Yasuda T,
  210. Triplett DA, Koike T. Anticardiolipin
  211. antibodies recognize b2-glycoprotein I
  212. structure altered by interacting with an
  213. oxygen modified solid phase surface. J
  214. Exp Med 1994;179:457-62.
  215. 29. Tincani A, Spatola L, Prati E, Allegri F,
  216. Ferremi P, Cattaneo R, et al. The anti-
  217. b2-glycoprotein I activity in human
  218. anti-phospholipid syndrome sera is
  219. due to monoreactive low-affinity
  220. autoantibodies directed to epitopes
  221. located on native b2-glycoprotein I
  222. and preserved during species' evolution.
  223. J Immunol 1996;157:5732-8.
  224. 30. Miyakis S, Giannakopoulos B, Krilis
  225. SA. b2 glycoprotein I-function in health
  226. and disease. Thromb Res 2004; 114:
  227. 335-46." name="eprints.referencetext" />
  228. <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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  232. <meta content="Lean, Sim Yee" name="DC.creator" />
  233. <meta content="Ellery, Paul E.W." name="DC.creator" />
  234. <meta content="Ivey, Leesa" name="DC.creator" />
  235. <meta content="Thom, J." name="DC.creator" />
  236. <meta content="Oostryck, R." name="DC.creator" />
  237. <meta content="Leahy, Michael" name="DC.creator" />
  238. <meta content="Baker, Ross I." name="DC.creator" />
  239. <meta content="Adams, M.J." name="DC.creator" />
  240. <meta content="321008 Haematology" name="DC.subject" />
  241. <meta content="300504 Immunology" name="DC.subject" />
  242. <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. 
  243. 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. 
  244. 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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  357.     <h1 class="ep_tm_pagetitle">The effects of tissue factor pathway inhibitor and anti-beta-2-glycoprotein-I IgG on thrombin generation</h1>
  358.     <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. &#13;
  359. 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&lt;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. &#13;
  360. 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&#13;
  361. 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 &gt; 321000 Clinical Sciences &gt; 321008 Haematology</a><br /><a href="http://eprints.utas.edu.au/view/subjects/300504.html">300000 Agricultural, Veterinary and Environmental Sciences &gt; 300500 Veterinary Sciences &gt; 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&amp;eprintid=843">item control page</a></p>
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