Anti‐tissue factor pathway inhibitor activity in patients with primary antiphospholipid syndrome
The association between antiphospholipid antibodies and an increased risk of thrombosis in antiphospholipid syndrome (aPS) patients is probably caused by numerous mechanisms, including the effects of antibodies to phospholipid‐binding proteins such as β2‐glycoprotein I and prothrombin. In this study...
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| Veröffentlicht in: | British journal of haematology 2001-08, Vol.114 (2), p.375-379 |
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| creator | Adams, Murray J. Donohoe, Siobhán Mackie, Ian J. Machin, Samuel J. |
| description | The association between antiphospholipid antibodies and an increased risk of thrombosis in antiphospholipid syndrome (aPS) patients is probably caused by numerous mechanisms, including the effects of antibodies to phospholipid‐binding proteins such as β2‐glycoprotein I and prothrombin. In this study, we investigated the inhibition of tissue factor pathway inhibitor (TFPI) in 33 patients with primary antiphospholipid syndrome (PAPS). TFPI was measured in PAPS patients using an amidolytic assay, dependent on the generation of activated factor X (Fxa), and this was compared with 55 healthy subjects. Functional levels of TFPI (mean ± SD) were significantly lower in PAPS patients (0·89 ± 0·37 U/ml) than the control group (1·05 ± 0·15 U/ml) (P = 0·02). The difference was caused by a subset of five patients who had TFPI levels below the lower 99% confidence interval of the normal reference range, representing increased FXa generation in the assay system. IgG fractions were isolated from these five patients and five control subjects, then incorporated into normal plasma to measure FXa generation in the TFPI assay system. FXa generation was increased when polyclonal rabbit anti‐human TFPI IgG (P |
| doi_str_mv | 10.1046/j.1365-2141.2001.02923.x |
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In this study, we investigated the inhibition of tissue factor pathway inhibitor (TFPI) in 33 patients with primary antiphospholipid syndrome (PAPS). TFPI was measured in PAPS patients using an amidolytic assay, dependent on the generation of activated factor X (Fxa), and this was compared with 55 healthy subjects. Functional levels of TFPI (mean ± SD) were significantly lower in PAPS patients (0·89 ± 0·37 U/ml) than the control group (1·05 ± 0·15 U/ml) (P = 0·02). The difference was caused by a subset of five patients who had TFPI levels below the lower 99% confidence interval of the normal reference range, representing increased FXa generation in the assay system. IgG fractions were isolated from these five patients and five control subjects, then incorporated into normal plasma to measure FXa generation in the TFPI assay system. FXa generation was increased when polyclonal rabbit anti‐human TFPI IgG (P < 0·0001) or PAPS IgG (P = 0·0001) were added to normal plasma, demonstrating inhibition of TFPI. The apparent anti‐TFPI activity demonstrated in the five subjects with PAPS in this study may represent a significant new mechanism for thrombosis in patients with aPS, as it implies that increased tissue factor FVIIa‐mediated thrombin generation might occur.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1046/j.1365-2141.2001.02923.x</identifier><identifier>PMID: 11529859</identifier><identifier>CODEN: BJHEAL</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Adult ; Aged ; antiphospholipid syndrome ; Antiphospholipid Syndrome - blood ; anti‐TFPI activity ; Biological and medical sciences ; Case-Control Studies ; factor Xa ; Factor Xa - metabolism ; Female ; Hematologic and hematopoietic diseases ; Hematology ; Humans ; Immunoglobulin G - metabolism ; Lipoproteins - blood ; Male ; Medical sciences ; Middle Aged ; Platelet diseases and coagulopathies ; TFPI ; thrombosis ; Thrombosis - blood</subject><ispartof>British journal of haematology, 2001-08, Vol.114 (2), p.375-379</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright Blackwell Scientific Publications Ltd. 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In this study, we investigated the inhibition of tissue factor pathway inhibitor (TFPI) in 33 patients with primary antiphospholipid syndrome (PAPS). TFPI was measured in PAPS patients using an amidolytic assay, dependent on the generation of activated factor X (Fxa), and this was compared with 55 healthy subjects. Functional levels of TFPI (mean ± SD) were significantly lower in PAPS patients (0·89 ± 0·37 U/ml) than the control group (1·05 ± 0·15 U/ml) (P = 0·02). The difference was caused by a subset of five patients who had TFPI levels below the lower 99% confidence interval of the normal reference range, representing increased FXa generation in the assay system. IgG fractions were isolated from these five patients and five control subjects, then incorporated into normal plasma to measure FXa generation in the TFPI assay system. FXa generation was increased when polyclonal rabbit anti‐human TFPI IgG (P < 0·0001) or PAPS IgG (P = 0·0001) were added to normal plasma, demonstrating inhibition of TFPI. The apparent anti‐TFPI activity demonstrated in the five subjects with PAPS in this study may represent a significant new mechanism for thrombosis in patients with aPS, as it implies that increased tissue factor FVIIa‐mediated thrombin generation might occur.</description><subject>Adult</subject><subject>Aged</subject><subject>antiphospholipid syndrome</subject><subject>Antiphospholipid Syndrome - blood</subject><subject>anti‐TFPI activity</subject><subject>Biological and medical sciences</subject><subject>Case-Control Studies</subject><subject>factor Xa</subject><subject>Factor Xa - metabolism</subject><subject>Female</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunoglobulin G - metabolism</subject><subject>Lipoproteins - blood</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Platelet diseases and coagulopathies</subject><subject>TFPI</subject><subject>thrombosis</subject><subject>Thrombosis - blood</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u1DAUhS0EokPhFVCEBLuk_olje8GiVNBSVWIDa8u_Go8ySbATprPjEXhGngS7E1GJFQvL1r3fubo-B4AKwQbBtrvYNYh0tMaoRQ2GEDUQC0ya-ydg87fxFGwghKzOAn4GXqS0yyCBFD0HZwhRLDgVG6Avhzn8_vlrDiktrvLKzGOsJjVvD-pYhWEbdCiVXA8_wlxKpRvcMKfqEOZtNcWwV_FYqTxo2o4pnz5MwVbpONg47t1L8MyrPrlX630Ovn36-PXqpr77cv356vKuNi3DpLZae8ws1pAjbyixhhMohHWCCNER5ixDhAjKjadUK9W2tHXac-KtpZprcg7eneZOcfy-uDTLfUjG9b0a3LgkyRAirMM8g2_-AXfjEoe8m0TFFcoYyxA_QSaOKUXn5fpRiaAsIcidLF7L4rUsIciHEOR9lr5e5y967-yjcHU9A29XQCWjeh_VYEJ65FoocNfBzL0_cYfQu-N_LyA_3N6UF_kDwMelRQ</recordid><startdate>200108</startdate><enddate>200108</enddate><creator>Adams, Murray J.</creator><creator>Donohoe, Siobhán</creator><creator>Mackie, Ian J.</creator><creator>Machin, Samuel J.</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><general>Blackwell Publishing Ltd</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200108</creationdate><title>Anti‐tissue factor pathway inhibitor activity in patients with primary antiphospholipid syndrome</title><author>Adams, Murray J. ; Donohoe, Siobhán ; Mackie, Ian J. ; Machin, Samuel J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4723-dbbf27d2b081fc53dc83099de9399637ed7133958cf55baa4454ebf83fdd5b8b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adult</topic><topic>Aged</topic><topic>antiphospholipid syndrome</topic><topic>Antiphospholipid Syndrome - blood</topic><topic>anti‐TFPI activity</topic><topic>Biological and medical sciences</topic><topic>Case-Control Studies</topic><topic>factor Xa</topic><topic>Factor Xa - metabolism</topic><topic>Female</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immunoglobulin G - metabolism</topic><topic>Lipoproteins - blood</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Platelet diseases and coagulopathies</topic><topic>TFPI</topic><topic>thrombosis</topic><topic>Thrombosis - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Adams, Murray J.</creatorcontrib><creatorcontrib>Donohoe, Siobhán</creatorcontrib><creatorcontrib>Mackie, Ian J.</creatorcontrib><creatorcontrib>Machin, Samuel J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Adams, Murray J.</au><au>Donohoe, Siobhán</au><au>Mackie, Ian J.</au><au>Machin, Samuel J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti‐tissue factor pathway inhibitor activity in patients with primary antiphospholipid syndrome</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2001-08</date><risdate>2001</risdate><volume>114</volume><issue>2</issue><spage>375</spage><epage>379</epage><pages>375-379</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><coden>BJHEAL</coden><abstract>The association between antiphospholipid antibodies and an increased risk of thrombosis in antiphospholipid syndrome (aPS) patients is probably caused by numerous mechanisms, including the effects of antibodies to phospholipid‐binding proteins such as β2‐glycoprotein I and prothrombin. 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FXa generation was increased when polyclonal rabbit anti‐human TFPI IgG (P < 0·0001) or PAPS IgG (P = 0·0001) were added to normal plasma, demonstrating inhibition of TFPI. The apparent anti‐TFPI activity demonstrated in the five subjects with PAPS in this study may represent a significant new mechanism for thrombosis in patients with aPS, as it implies that increased tissue factor FVIIa‐mediated thrombin generation might occur.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>11529859</pmid><doi>10.1046/j.1365-2141.2001.02923.x</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged antiphospholipid syndrome Antiphospholipid Syndrome - blood anti‐TFPI activity Biological and medical sciences Case-Control Studies factor Xa Factor Xa - metabolism Female Hematologic and hematopoietic diseases Hematology Humans Immunoglobulin G - metabolism Lipoproteins - blood Male Medical sciences Middle Aged Platelet diseases and coagulopathies TFPI thrombosis Thrombosis - blood |
| title | Anti‐tissue factor pathway inhibitor activity in patients with primary antiphospholipid syndrome |
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