Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis
Summary Essentials The role of increased factor VIII in cirrhosis‐induced hypercoagulability has never been demonstrated. Factor VIII and protein C effects were characterized by thrombin generation with thrombomodulin. Factor VIII elevation plays a significant role in cirrhosis‐induced plasma hyperc...
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| Veröffentlicht in: | Journal of thrombosis and haemostasis 2018-06, Vol.16 (6), p.1132-1140 |
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| creator | Sinegre, T. Duron, C. Lecompte, T. Pereira, B. Massoulier, S. Lamblin, G. Abergel, A. Lebreton, A. |
| description | Summary
Essentials
The role of increased factor VIII in cirrhosis‐induced hypercoagulability has never been demonstrated.
Factor VIII and protein C effects were characterized by thrombin generation with thrombomodulin.
Factor VIII elevation plays a significant role in cirrhosis‐induced plasma hypercoagulability.
Only protein C and factor VIII normalization led to thrombin generation similar to controls.
Summary
Background
In cirrhosis, thrombin generation (TG) studied in the presence of thrombomodulin (TM) indicates plasma hypercoagulability. Although the role of protein C (PC) deficiency has been investigated, the influence of an increase in the factor VIII level has never been addressed.
Objectives
We investigated the roles of high FVIII and low PC levels in increased TG in the presence of TM.
Methods
Blood samples were prospectively collected from 35 healthy controls and 93 patients with cirrhosis (Child–Turcotte–Pugh [CTP]‐A, n = 61; CTP‐B, n = 19; and CTP‐C, n = 13) and FVIII levels > 150% (n = 48) and/or PC levels |
| doi_str_mv | 10.1111/jth.14011 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_01846126v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2047983577</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4221-9a1355c2e6f965eef820220cb080f60c5faa1dafa70be1c3e8e6114294acfcf23</originalsourceid><addsrcrecordid>eNp1kU1v1DAQhi0EoqVw4A8gS1zgsK3txE5yrCpgg1biUrhas95x45U3DrZDlX-Pl22LhIQvY808eufjJeQtZ5e8vKt9Hi55zTh_Rs65rNpV01bq-eO_q6oz8iqlPWO8k4K9JGeik02jmDwnUz-aiJBwRy2YHCL90fc9nTwsiQJN7m501hkYM43BI3XjsZYOQIdlwmgC3M0ets67vNBpwDHkkqfB0gmywzEneu_yQI2LcQjJpdfkhQWf8M1DvCDfP3-6vVmvNt--9DfXm5WpheCrDnglpRGobKckom0FE4KZLWuZVcxIC8B3YKFhW-SmwhYV57XoajDWWFFdkI8n3QG8nqI7QFx0AKfX1xt9zDHe1ooL9YsX9sOJnWL4OWPK-uCSQe9hxDAnLQqrVCuVKuj7f9B9mONYNilU3XRtVS77t7mJIaWI9mkCzvTRMl0s038sK-y7B8V5e8DdE_noUQGuTsC987j8X0l_vV2fJH8D-iOgYQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2047983577</pqid></control><display><type>article</type><title>Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis</title><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Sinegre, T. ; Duron, C. ; Lecompte, T. ; Pereira, B. ; Massoulier, S. ; Lamblin, G. ; Abergel, A. ; Lebreton, A.</creator><creatorcontrib>Sinegre, T. ; Duron, C. ; Lecompte, T. ; Pereira, B. ; Massoulier, S. ; Lamblin, G. ; Abergel, A. ; Lebreton, A.</creatorcontrib><description>Summary
Essentials
The role of increased factor VIII in cirrhosis‐induced hypercoagulability has never been demonstrated.
Factor VIII and protein C effects were characterized by thrombin generation with thrombomodulin.
Factor VIII elevation plays a significant role in cirrhosis‐induced plasma hypercoagulability.
Only protein C and factor VIII normalization led to thrombin generation similar to controls.
Summary
Background
In cirrhosis, thrombin generation (TG) studied in the presence of thrombomodulin (TM) indicates plasma hypercoagulability. Although the role of protein C (PC) deficiency has been investigated, the influence of an increase in the factor VIII level has never been addressed.
Objectives
We investigated the roles of high FVIII and low PC levels in increased TG in the presence of TM.
Methods
Blood samples were prospectively collected from 35 healthy controls and 93 patients with cirrhosis (Child–Turcotte–Pugh [CTP]‐A, n = 61; CTP‐B, n = 19; and CTP‐C, n = 13) and FVIII levels > 150% (n = 48) and/or PC levels < 70% (n = 88). TG was performed with tissue factor (5 pm), phospholipids, and TM (4 nm). FVIII and PC levels were normalized by adding an inhibitory anti‐FVIII antibody and exogenous PC, respectively.
Results
The endogenous thrombin potential (ETP) in the presence of TM was higher in patients than in controls. After FVIII normalization, the ETP (median) decreased from 929 nm min to 621 nm min (CTP‐A), 1122 nm min to 1082 nm min (CTP‐B), and 1221 nm min to 1143 nm min (CTP‐C); after PC normalization, it decreased from 776 nm min to 566 nm min (CTP‐A), 1120 nm min to 790 nm min (CTP‐B), and 995 nm min to 790 nm min (CTP‐C). The ETP was reduced by 17% and 30%, respectively, but normal TG was not restored. When both FVIII and PC levels were normalized, the ETP decreased from 929 nm min to 340 nm min (CTP‐A), 1122 nm min to 506 nm min (CTP‐B), and 1226 nm min to 586 nm min (CTP‐C), becoming similar to control levels.
Conclusion
Cirrhosis‐induced plasma hypercoagulability, as demonstrated in these experimental conditions, can be partly explained by opposite changes in two factors: PC level (decrease) and FVIII level (increase).</description><identifier>ISSN: 1538-7933</identifier><identifier>ISSN: 1538-7836</identifier><identifier>EISSN: 1538-7836</identifier><identifier>DOI: 10.1111/jth.14011</identifier><identifier>PMID: 29577605</identifier><language>eng</language><publisher>England: Elsevier Limited</publisher><subject>Cardiology and cardiovascular system ; Cirrhosis ; Coagulation factors ; factor VIII ; Human health and pathology ; hypercoagulability ; Life Sciences ; Liver cirrhosis ; Phenotypes ; Phospholipids ; Protein C ; Protein deficiency ; protein C ; Thrombin ; thrombin generation ; Thrombomodulin ; Tissue factor</subject><ispartof>Journal of thrombosis and haemostasis, 2018-06, Vol.16 (6), p.1132-1140</ispartof><rights>2018 International Society on Thrombosis and Haemostasis</rights><rights>2018 International Society on Thrombosis and Haemostasis.</rights><rights>Copyright © 2018 International Society on Thrombosis and Haemostasis</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4221-9a1355c2e6f965eef820220cb080f60c5faa1dafa70be1c3e8e6114294acfcf23</citedby><cites>FETCH-LOGICAL-c4221-9a1355c2e6f965eef820220cb080f60c5faa1dafa70be1c3e8e6114294acfcf23</cites><orcidid>0000-0003-0945-1425 ; 0000-0001-7480-1052</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29577605$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01846126$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Sinegre, T.</creatorcontrib><creatorcontrib>Duron, C.</creatorcontrib><creatorcontrib>Lecompte, T.</creatorcontrib><creatorcontrib>Pereira, B.</creatorcontrib><creatorcontrib>Massoulier, S.</creatorcontrib><creatorcontrib>Lamblin, G.</creatorcontrib><creatorcontrib>Abergel, A.</creatorcontrib><creatorcontrib>Lebreton, A.</creatorcontrib><title>Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis</title><title>Journal of thrombosis and haemostasis</title><addtitle>J Thromb Haemost</addtitle><description>Summary
Essentials
The role of increased factor VIII in cirrhosis‐induced hypercoagulability has never been demonstrated.
Factor VIII and protein C effects were characterized by thrombin generation with thrombomodulin.
Factor VIII elevation plays a significant role in cirrhosis‐induced plasma hypercoagulability.
Only protein C and factor VIII normalization led to thrombin generation similar to controls.
Summary
Background
In cirrhosis, thrombin generation (TG) studied in the presence of thrombomodulin (TM) indicates plasma hypercoagulability. Although the role of protein C (PC) deficiency has been investigated, the influence of an increase in the factor VIII level has never been addressed.
Objectives
We investigated the roles of high FVIII and low PC levels in increased TG in the presence of TM.
Methods
Blood samples were prospectively collected from 35 healthy controls and 93 patients with cirrhosis (Child–Turcotte–Pugh [CTP]‐A, n = 61; CTP‐B, n = 19; and CTP‐C, n = 13) and FVIII levels > 150% (n = 48) and/or PC levels < 70% (n = 88). TG was performed with tissue factor (5 pm), phospholipids, and TM (4 nm). FVIII and PC levels were normalized by adding an inhibitory anti‐FVIII antibody and exogenous PC, respectively.
Results
The endogenous thrombin potential (ETP) in the presence of TM was higher in patients than in controls. After FVIII normalization, the ETP (median) decreased from 929 nm min to 621 nm min (CTP‐A), 1122 nm min to 1082 nm min (CTP‐B), and 1221 nm min to 1143 nm min (CTP‐C); after PC normalization, it decreased from 776 nm min to 566 nm min (CTP‐A), 1120 nm min to 790 nm min (CTP‐B), and 995 nm min to 790 nm min (CTP‐C). The ETP was reduced by 17% and 30%, respectively, but normal TG was not restored. When both FVIII and PC levels were normalized, the ETP decreased from 929 nm min to 340 nm min (CTP‐A), 1122 nm min to 506 nm min (CTP‐B), and 1226 nm min to 586 nm min (CTP‐C), becoming similar to control levels.
Conclusion
Cirrhosis‐induced plasma hypercoagulability, as demonstrated in these experimental conditions, can be partly explained by opposite changes in two factors: PC level (decrease) and FVIII level (increase).</description><subject>Cardiology and cardiovascular system</subject><subject>Cirrhosis</subject><subject>Coagulation factors</subject><subject>factor VIII</subject><subject>Human health and pathology</subject><subject>hypercoagulability</subject><subject>Life Sciences</subject><subject>Liver cirrhosis</subject><subject>Phenotypes</subject><subject>Phospholipids</subject><subject>Protein C</subject><subject>Protein deficiency</subject><subject>protein C</subject><subject>Thrombin</subject><subject>thrombin generation</subject><subject>Thrombomodulin</subject><subject>Tissue factor</subject><issn>1538-7933</issn><issn>1538-7836</issn><issn>1538-7836</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kU1v1DAQhi0EoqVw4A8gS1zgsK3txE5yrCpgg1biUrhas95x45U3DrZDlX-Pl22LhIQvY808eufjJeQtZ5e8vKt9Hi55zTh_Rs65rNpV01bq-eO_q6oz8iqlPWO8k4K9JGeik02jmDwnUz-aiJBwRy2YHCL90fc9nTwsiQJN7m501hkYM43BI3XjsZYOQIdlwmgC3M0ets67vNBpwDHkkqfB0gmywzEneu_yQI2LcQjJpdfkhQWf8M1DvCDfP3-6vVmvNt--9DfXm5WpheCrDnglpRGobKckom0FE4KZLWuZVcxIC8B3YKFhW-SmwhYV57XoajDWWFFdkI8n3QG8nqI7QFx0AKfX1xt9zDHe1ooL9YsX9sOJnWL4OWPK-uCSQe9hxDAnLQqrVCuVKuj7f9B9mONYNilU3XRtVS77t7mJIaWI9mkCzvTRMl0s038sK-y7B8V5e8DdE_noUQGuTsC987j8X0l_vV2fJH8D-iOgYQ</recordid><startdate>201806</startdate><enddate>201806</enddate><creator>Sinegre, T.</creator><creator>Duron, C.</creator><creator>Lecompte, T.</creator><creator>Pereira, B.</creator><creator>Massoulier, S.</creator><creator>Lamblin, G.</creator><creator>Abergel, A.</creator><creator>Lebreton, A.</creator><general>Elsevier Limited</general><general>Wiley</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0003-0945-1425</orcidid><orcidid>https://orcid.org/0000-0001-7480-1052</orcidid></search><sort><creationdate>201806</creationdate><title>Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis</title><author>Sinegre, T. ; Duron, C. ; Lecompte, T. ; Pereira, B. ; Massoulier, S. ; Lamblin, G. ; Abergel, A. ; Lebreton, A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4221-9a1355c2e6f965eef820220cb080f60c5faa1dafa70be1c3e8e6114294acfcf23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Cardiology and cardiovascular system</topic><topic>Cirrhosis</topic><topic>Coagulation factors</topic><topic>factor VIII</topic><topic>Human health and pathology</topic><topic>hypercoagulability</topic><topic>Life Sciences</topic><topic>Liver cirrhosis</topic><topic>Phenotypes</topic><topic>Phospholipids</topic><topic>Protein C</topic><topic>Protein deficiency</topic><topic>protein C</topic><topic>Thrombin</topic><topic>thrombin generation</topic><topic>Thrombomodulin</topic><topic>Tissue factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sinegre, T.</creatorcontrib><creatorcontrib>Duron, C.</creatorcontrib><creatorcontrib>Lecompte, T.</creatorcontrib><creatorcontrib>Pereira, B.</creatorcontrib><creatorcontrib>Massoulier, S.</creatorcontrib><creatorcontrib>Lamblin, G.</creatorcontrib><creatorcontrib>Abergel, A.</creatorcontrib><creatorcontrib>Lebreton, A.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Journal of thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sinegre, T.</au><au>Duron, C.</au><au>Lecompte, T.</au><au>Pereira, B.</au><au>Massoulier, S.</au><au>Lamblin, G.</au><au>Abergel, A.</au><au>Lebreton, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis</atitle><jtitle>Journal of thrombosis and haemostasis</jtitle><addtitle>J Thromb Haemost</addtitle><date>2018-06</date><risdate>2018</risdate><volume>16</volume><issue>6</issue><spage>1132</spage><epage>1140</epage><pages>1132-1140</pages><issn>1538-7933</issn><issn>1538-7836</issn><eissn>1538-7836</eissn><abstract>Summary
Essentials
The role of increased factor VIII in cirrhosis‐induced hypercoagulability has never been demonstrated.
Factor VIII and protein C effects were characterized by thrombin generation with thrombomodulin.
Factor VIII elevation plays a significant role in cirrhosis‐induced plasma hypercoagulability.
Only protein C and factor VIII normalization led to thrombin generation similar to controls.
Summary
Background
In cirrhosis, thrombin generation (TG) studied in the presence of thrombomodulin (TM) indicates plasma hypercoagulability. Although the role of protein C (PC) deficiency has been investigated, the influence of an increase in the factor VIII level has never been addressed.
Objectives
We investigated the roles of high FVIII and low PC levels in increased TG in the presence of TM.
Methods
Blood samples were prospectively collected from 35 healthy controls and 93 patients with cirrhosis (Child–Turcotte–Pugh [CTP]‐A, n = 61; CTP‐B, n = 19; and CTP‐C, n = 13) and FVIII levels > 150% (n = 48) and/or PC levels < 70% (n = 88). TG was performed with tissue factor (5 pm), phospholipids, and TM (4 nm). FVIII and PC levels were normalized by adding an inhibitory anti‐FVIII antibody and exogenous PC, respectively.
Results
The endogenous thrombin potential (ETP) in the presence of TM was higher in patients than in controls. After FVIII normalization, the ETP (median) decreased from 929 nm min to 621 nm min (CTP‐A), 1122 nm min to 1082 nm min (CTP‐B), and 1221 nm min to 1143 nm min (CTP‐C); after PC normalization, it decreased from 776 nm min to 566 nm min (CTP‐A), 1120 nm min to 790 nm min (CTP‐B), and 995 nm min to 790 nm min (CTP‐C). The ETP was reduced by 17% and 30%, respectively, but normal TG was not restored. When both FVIII and PC levels were normalized, the ETP decreased from 929 nm min to 340 nm min (CTP‐A), 1122 nm min to 506 nm min (CTP‐B), and 1226 nm min to 586 nm min (CTP‐C), becoming similar to control levels.
Conclusion
Cirrhosis‐induced plasma hypercoagulability, as demonstrated in these experimental conditions, can be partly explained by opposite changes in two factors: PC level (decrease) and FVIII level (increase).</abstract><cop>England</cop><pub>Elsevier Limited</pub><pmid>29577605</pmid><doi>10.1111/jth.14011</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-0945-1425</orcidid><orcidid>https://orcid.org/0000-0001-7480-1052</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Cardiology and cardiovascular system Cirrhosis Coagulation factors factor VIII Human health and pathology hypercoagulability Life Sciences Liver cirrhosis Phenotypes Phospholipids Protein C Protein deficiency protein C Thrombin thrombin generation Thrombomodulin Tissue factor |
| title | Increased factor VIII plays a significant role in plasma hypercoagulability phenotype of patients with cirrhosis |
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