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  5.     <title>UTas ePrints - Anti-tissue factor pathway inhibitor activity in patients with primary antiphospholipid syndrome</title>
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  13.     <meta content="Adams, M.J." name="eprints.creators_name" />
  14. <meta content="Donohoe, S." name="eprints.creators_name" />
  15. <meta content="Mackie, I.J." name="eprints.creators_name" />
  16. <meta content="Machin, S.J." name="eprints.creators_name" />
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  18. <meta content="2007-09-10" name="eprints.datestamp" />
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  21. <meta content="Anti-tissue factor pathway inhibitor activity in patients with
  22. primary antiphospholipid syndrome" name="eprints.title" />
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  26. <meta content="TFPI, antiphospholipid syndrome, anti-TFPI
  27. activity, factor Xa, thrombosis." name="eprints.keywords" />
  28. <meta content="The definitive version is available at www.blackwell-synergy.com" name="eprints.note" />
  29. <meta content="The association between antiphospholipid antibodies
  30. and an increased risk of thrombosis in antiphospholipid
  31. syndrome (aPS) patients is probably caused by
  32. numerous mechanisms, including the effects of antibodies
  33. to phospholipid-binding proteins such as b2-glycoprotein I
  34. and prothrombin. In this study, we investigated the
  35. inhibition of tissue factor pathway inhibitor (TFPI) in 33
  36. patients with primary antiphospholipid syndrome (PAPS).
  37. TFPI was measured in PAPS patients using an amidolytic
  38. assay, dependent on the generation of activated factor X
  39. (Fxa), and this was compared with 55 healthy subjects.
  40. Functional levels of TFPI (mean plus or minus SD) were significantly
  41. lower in PAPS patients (0.89 plus or minus 0.37 U/ml) than the
  42. control group (1.05 plus or minus 0.15 U/ml) (P = 0.02). The difference
  43. was caused by a subset of five patients who had TFPI
  44. levels below the lower 99% confidence interval of the
  45. normal reference range, representing increased FXa generation
  46. in the assay system. IgG fractions were isolated from
  47. these five patients and five control subjects, then incorporated
  48. into normal plasma to measure FXa generation in the
  49. TFPI assay system. FXa generation was increased when
  50. polyclonal rabbit anti-human TFPI IgG (P less than 0.0001) or
  51. PAPS IgG (P = 0.0001) were added to normal plasma,
  52. demonstrating inhibition of TFPI. The apparent anti-TFPI
  53. activity demonstrated in the five subjects with PAPS in this
  54. study may represent a significant new mechanism for
  55. thrombosis in patients with aPS, as it implies that increased
  56. tissue factor FVIIa-mediated thrombin generation might
  57. occur." name="eprints.abstract" />
  58. <meta content="2001" name="eprints.date" />
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  60. <meta content="British Journal of Haematology" name="eprints.publication" />
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  62. <meta content="375-379" name="eprints.pagerange" />
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  66. <meta content="http://dx.doi.org/10.1046/j.1365-2141.2001.02923.x" name="eprints.official_url" />
  67. <meta content="Adams, M.J. &amp; Oostryck, R. (1997) Further investigations of lupus
  68. anticoagulant interference in a functional assay for tissue factor
  69. pathway inhibitor. Thrombosis Research, 87, 245±249.
  70. Adams, M.J., Dunstan, R.A. &amp; Oostryck, R. (1995) Interference by
  71. lupus anticoagulant in a functional assay for tissue factor
  72. pathway inhibitor. Thrombosis Research, 80, 435±550.
  73. Amengual, O., Atsumi, T., Khamashta, M.A. &amp; Hughes, G.R. (1998)
  74. The role of the tissue factor pathway in the hypercoagulable state
  75. in patients with the antiphospholipid syndrome. Thrombosis and
  76. Haemostasis, 79, 276±281.
  77. Broze, G.J., Warren, L.A., Novotny, W.F., Higuchi, D.A., Girard, J.J. &amp;
  78. Miletich, J.P. (1988) The lipoprotein-associated coagulation
  79. inhibitor that inhibits the factor VII-tissue factor complex also
  80. inhibits factor Xa: insight into its possible mechanism of action.
  81. Blood, 71, 335±343.
  82. Cakir, B., Arnett, F.C. &amp; Roubey, R.A.S. (2000) Autoantibodies to
  83. tissue factor pathway inhibitor (TFPI) are associated with arterial
  84. thrombosis/stroke. Journal of Autoimmunity, 15, A11(Abstract).
  85. Exner, T., Triplett, D.A., Taberner, D. &amp; Machin, S.J. (1991)
  86. Guidelines for testing and revised criteria for lupus anticoagulants.
  87. Thrombosis and Haemostasis, 65, 320±322.
  88. Greaves, M., Cohen, H., Machin, S.J. &amp; Mackie, I.J. (2000) Guidelines
  89. on the investigation and management of the antiphospholipid
  90. syndrome. British Journal of Haematology, 109, 704±715.
  91. Harris, E.N. &amp; Hughes, G.R. (1987) Standardising the anticardiolipin
  92. antibody test. Lancet., 1, 277.
  93. Harris, E.N., Baguley, E., Asherson, R.A. &amp; Hughes, G.R. (1987)
  94. Clinical and serological features of the `antiphospholipid syndrome'.
  95. British Journal of Rheumatology, 26, 19.
  96. Hughes, G.R., Harris, N.N. &amp; Gharavi, A.E. (1986) The anticardiolipin
  97. syndrome. Journal of Rheumatology, 13, 486±489.
  98. Jacobsen, E.M., Sandset, P.M. &amp; Wisloff, F. (1999) Do antiphospholipid
  99. antibodies interfere with tissue factor pathway inhibitor?
  100. Thrombosis Research, 94, 213±220.
  101. Kiraz, S., Ertenli, I., Benekli, M., Haznedaroglu, I.C., Calguneri, M.,
  102. Celik, I., Apras, S. &amp; Kirazli, S. (1999) Clinical significance of
  103. hemostatic markers and thrombomodulin in systemic lupus
  104. erythematosus: evidence for a prothrombotic state. Lupus, 8,
  105. 737±741.
  106. Love, P.E. &amp; Santoro, S.A. (1990) Antiphospholipid antibodies:
  107. anticardiolipin and the lupus anticoagulant in systemic lupus
  108. erythematosus (SLE) and in non-SLE disorders. Prevalence and
  109. clinical significance. Annals of Internal Medicine, 112, 682±698.
  110. McNally, T., Mackie, I.J., Machin, S.J. &amp; Isenberg, D.A. (1995)
  111. Increased levels of beta 2-glycoprotein-I antigen and beta 2-
  112. glycoprotein-I binding antibodies are associated with a history of
  113. thromboembolic complications in patients with SLE and primary
  114. antiphospholipid syndrome. British Journal of Rheumatology, 34,
  115. 1031±1036.
  116. McNeil, H.P., Simpson, R.J., Chesterman, C.N. &amp; Krilis, S.A. (1990)
  117. Anti-phospholipid antibodies are directed against a complex
  118. antigen that includes a lipid-binding inhibitor of coagulation:
  119. beta 2-glycoprotein I (apoliporotein H). Proceedings of the National
  120. Academy of Sciences of the United States of America, 87, 4120±
  121. 4114.
  122. Salemink, I., Blezer, R., Willems, G.M., Galli, M., Bevers, E. &amp;
  123. Lindhout, T. (2000) Antibodies to û2-glycoprotein-I associated
  124. with antiphospholipid syndrome suppress the inhibitory activity
  125. of tissue factor pathway inhibitor. Thrombosis and Haemostasis, 84,
  126. 653±656.
  127. Sandset, P.M., Abildgaard, U. &amp; Pettersen, M. (1987) A sensitive
  128. assay of extrinsic coagulation pathway inhibitor (EPI) in plasma
  129. and plasma fractions. Thrombosis Research, 47, 389±400.
  130. Wakita, Y., Wada, H., Nakase, T., Nakasaki, T., Shimura, M.,
  131. Hiyoyama, K., Mori, Y., Gabazza, E.C., Nishikawa, M., Deguchi, K.
  132. &amp; Shiku, H. (1999) Aberrations of the tissue factor pathway in
  133. patients positive for lupus anticoagulant. Clinical and Applied
  134. Thrombosis and Haemostasis, 5, 10±15.
  135. Wilson, W.A., Gharavi, A.E., Koike, T., Lockshin, M.D., Branch,
  136. D.W., Piette, J.C., Brey, R., Derksen, R., Harris, E.N., Hughes, G.R.,
  137. Triplett, D.A. &amp; Khamashta, M.A. (1999) International consensus
  138. statement on preliminary classification criteria for definite
  139. antiphospholipid syndrome: report of an international workshop.
  140. Arthritis and Rheumatism, 42, 1309±1311." name="eprints.referencetext" />
  141. <meta content="Adams, M.J. and Donohoe, S. and Mackie, I.J. and Machin, S.J. (2001) Anti-tissue factor pathway inhibitor activity in patients with primary antiphospholipid syndrome. British Journal of Haematology, 114 . pp. 375-379." name="eprints.citation" />
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  149. <meta content="Machin, S.J." name="DC.creator" />
  150. <meta content="321008 Haematology" name="DC.subject" />
  151. <meta content="The association between antiphospholipid antibodies
  152. and an increased risk of thrombosis in antiphospholipid
  153. syndrome (aPS) patients is probably caused by
  154. numerous mechanisms, including the effects of antibodies
  155. to phospholipid-binding proteins such as b2-glycoprotein I
  156. and prothrombin. In this study, we investigated the
  157. inhibition of tissue factor pathway inhibitor (TFPI) in 33
  158. patients with primary antiphospholipid syndrome (PAPS).
  159. TFPI was measured in PAPS patients using an amidolytic
  160. assay, dependent on the generation of activated factor X
  161. (Fxa), and this was compared with 55 healthy subjects.
  162. Functional levels of TFPI (mean plus or minus SD) were significantly
  163. lower in PAPS patients (0.89 plus or minus 0.37 U/ml) than the
  164. control group (1.05 plus or minus 0.15 U/ml) (P = 0.02). The difference
  165. was caused by a subset of five patients who had TFPI
  166. levels below the lower 99% confidence interval of the
  167. normal reference range, representing increased FXa generation
  168. in the assay system. IgG fractions were isolated from
  169. these five patients and five control subjects, then incorporated
  170. into normal plasma to measure FXa generation in the
  171. TFPI assay system. FXa generation was increased when
  172. polyclonal rabbit anti-human TFPI IgG (P less than 0.0001) or
  173. PAPS IgG (P = 0.0001) were added to normal plasma,
  174. demonstrating inhibition of TFPI. The apparent anti-TFPI
  175. activity demonstrated in the five subjects with PAPS in this
  176. study may represent a significant new mechanism for
  177. thrombosis in patients with aPS, as it implies that increased
  178. tissue factor FVIIa-mediated thrombin generation might
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  293.     <h1 class="ep_tm_pagetitle">Anti-tissue factor pathway inhibitor activity in patients with primary antiphospholipid syndrome</h1>
  294.     <p style="margin-bottom: 1em" class="not_ep_block"><span class="person_name">Adams, M.J.</span> and <span class="person_name">Donohoe, S.</span> and <span class="person_name">Mackie, I.J.</span> and <span class="person_name">Machin, S.J.</span> (2001) <xhtml:em>Anti-tissue factor pathway inhibitor activity in patients with primary antiphospholipid syndrome.</xhtml:em> British Journal of Haematology, 114 . pp. 375-379.</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/1780/1/Adams_et_al_2001.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/1780/1/Adams_et_al_2001.pdf"><span class="ep_document_citation">PDF</span></a> - Full text restricted - Requires a PDF viewer<br />151Kb</td></tr></table><p style="margin-bottom: 1em" class="not_ep_block">Official URL: <a href="http://dx.doi.org/10.1046/j.1365-2141.2001.02923.x">http://dx.doi.org/10.1046/j.1365-2141.2001.02923.x</a></p><div class="not_ep_block"><h2>Abstract</h2><p style="padding-bottom: 16px; text-align: left; margin: 1em auto 0em auto">The association between antiphospholipid antibodies&#13;
  295. and an increased risk of thrombosis in antiphospholipid&#13;
  296. syndrome (aPS) patients is probably caused by&#13;
  297. numerous mechanisms, including the effects of antibodies&#13;
  298. to phospholipid-binding proteins such as b2-glycoprotein I&#13;
  299. and prothrombin. In this study, we investigated the&#13;
  300. inhibition of tissue factor pathway inhibitor (TFPI) in 33&#13;
  301. patients with primary antiphospholipid syndrome (PAPS).&#13;
  302. TFPI was measured in PAPS patients using an amidolytic&#13;
  303. assay, dependent on the generation of activated factor X&#13;
  304. (Fxa), and this was compared with 55 healthy subjects.&#13;
  305. Functional levels of TFPI (mean plus or minus SD) were significantly&#13;
  306. lower in PAPS patients (0.89 plus or minus 0.37 U/ml) than the&#13;
  307. control group (1.05 plus or minus 0.15 U/ml) (P = 0.02). The difference&#13;
  308. was caused by a subset of five patients who had TFPI&#13;
  309. levels below the lower 99% confidence interval of the&#13;
  310. normal reference range, representing increased FXa generation&#13;
  311. in the assay system. IgG fractions were isolated from&#13;
  312. these five patients and five control subjects, then incorporated&#13;
  313. into normal plasma to measure FXa generation in the&#13;
  314. TFPI assay system. FXa generation was increased when&#13;
  315. polyclonal rabbit anti-human TFPI IgG (P less than 0.0001) or&#13;
  316. PAPS IgG (P = 0.0001) were added to normal plasma,&#13;
  317. demonstrating inhibition of TFPI. The apparent anti-TFPI&#13;
  318. activity demonstrated in the five subjects with PAPS in this&#13;
  319. study may represent a significant new mechanism for&#13;
  320. thrombosis in patients with aPS, as it implies that increased&#13;
  321. tissue factor FVIIa-mediated thrombin generation might&#13;
  322. occur.</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">Additional Information:</th><td valign="top" class="ep_row">The definitive version is available at www.blackwell-synergy.com</td></tr><tr><th valign="top" class="ep_row">Keywords:</th><td valign="top" class="ep_row">TFPI, antiphospholipid syndrome, anti-TFPI&#13;
  323. activity, factor Xa, thrombosis.</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">1780</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">10 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=1780;">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=1780">item control page</a></p>
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