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Plasma levels of plasminogen activator inhibitor‐1 and bleeding phenotype in patients with von Willebrand disease

Introduction von Willebrand disease (VWD) is the most common inherited bleeding disorder. In VWD patients, large variations in bleeding tendency are observed, which cannot be completely explained by the variation in von Willebrand factor levels or activities. Thus, there must be additional factors,...

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Published in:Haemophilia : the official journal of the World Federation of Hemophilia 2017-05, Vol.23 (3), p.437-443
Main Authors: Abdul, S., Boender, J., Malfliet, J. J. M. C., Eikenboom, J., Fijn van Draat, K., Mauser‐Bunschoten, E. P., Meijer, K., Meris, J., Laros‐van Gorkom, B. A. P., Bom, J. G., Leebeek, F. W. G., Rijken, D. C., Uitte de Willige, S., Fijnvandraat, K, Coppens, M, Kors, A, Jonkers, H, Boersma, R, Beckers, A, Granzen, B, Tamminga, J, Linden, W, Ypma, F, Smiers, W, Brons, P, Nijziel, M, Cnossen, H
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cited_by cdi_FETCH-LOGICAL-c3886-874b82fad92fc60ab778c25058b5d3a9ff873c3d71982c26a673b245803b994e3
cites cdi_FETCH-LOGICAL-c3886-874b82fad92fc60ab778c25058b5d3a9ff873c3d71982c26a673b245803b994e3
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container_title Haemophilia : the official journal of the World Federation of Hemophilia
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creator Abdul, S.
Boender, J.
Malfliet, J. J. M. C.
Eikenboom, J.
Fijn van Draat, K.
Mauser‐Bunschoten, E. P.
Meijer, K.
Meris, J.
Laros‐van Gorkom, B. A. P.
Bom, J. G.
Leebeek, F. W. G.
Rijken, D. C.
Uitte de Willige, S.
Fijnvandraat, K
Coppens, M
Kors, A
Jonkers, H
Boersma, R
Beckers, A
Granzen, B
Tamminga, J
Linden, W
Ypma, F
Smiers, W
Brons, P
Nijziel, M
Cnossen, H
description Introduction von Willebrand disease (VWD) is the most common inherited bleeding disorder. In VWD patients, large variations in bleeding tendency are observed, which cannot be completely explained by the variation in von Willebrand factor levels or activities. Thus, there must be additional factors, for instance, changes in fibrinolysis that have an effect on the variation in bleeding tendency in VWD patients. Aim To investigate whether plasminogen activator inhibitor‐1 (PAI‐1) level influences the variation in bleeding tendency in VWD patients. Methods PAI‐1 antigen levels were measured in the plasma of 633 patients with moderate or severe VWD who participated in the ‘Willebrand in the Netherlands’ (WiN) study, a nationwide multicentre cross‐sectional study. Bleeding severity was assessed using the Tosetto bleeding score. Results PAI‐1 levels increased with age (Spearman's rho: 0.225, P 
doi_str_mv 10.1111/hae.13206
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J. M. C. ; Eikenboom, J. ; Fijn van Draat, K. ; Mauser‐Bunschoten, E. P. ; Meijer, K. ; Meris, J. ; Laros‐van Gorkom, B. A. P. ; Bom, J. G. ; Leebeek, F. W. G. ; Rijken, D. C. ; Uitte de Willige, S. ; Fijnvandraat, K ; Coppens, M ; Kors, A ; Jonkers, H ; Boersma, R ; Beckers, A ; Granzen, B ; Tamminga, J ; Linden, W ; Ypma, F ; Smiers, W ; Brons, P ; Nijziel, M ; Cnossen, H</creator><creatorcontrib>Abdul, S. ; Boender, J. ; Malfliet, J. J. M. C. ; Eikenboom, J. ; Fijn van Draat, K. ; Mauser‐Bunschoten, E. P. ; Meijer, K. ; Meris, J. ; Laros‐van Gorkom, B. A. P. ; Bom, J. G. ; Leebeek, F. W. G. ; Rijken, D. C. ; Uitte de Willige, S. ; Fijnvandraat, K ; Coppens, M ; Kors, A ; Jonkers, H ; Boersma, R ; Beckers, A ; Granzen, B ; Tamminga, J ; Linden, W ; Ypma, F ; Smiers, W ; Brons, P ; Nijziel, M ; Cnossen, H ; WIN study group</creatorcontrib><description>Introduction von Willebrand disease (VWD) is the most common inherited bleeding disorder. In VWD patients, large variations in bleeding tendency are observed, which cannot be completely explained by the variation in von Willebrand factor levels or activities. Thus, there must be additional factors, for instance, changes in fibrinolysis that have an effect on the variation in bleeding tendency in VWD patients. Aim To investigate whether plasminogen activator inhibitor‐1 (PAI‐1) level influences the variation in bleeding tendency in VWD patients. Methods PAI‐1 antigen levels were measured in the plasma of 633 patients with moderate or severe VWD who participated in the ‘Willebrand in the Netherlands’ (WiN) study, a nationwide multicentre cross‐sectional study. Bleeding severity was assessed using the Tosetto bleeding score. Results PAI‐1 levels increased with age (Spearman's rho: 0.225, P &lt; 0.001) and were higher in men (23 [IQR 12–60] vs. 20 [IQR 10–44] ng mL−1 in women, P = 0.039), whereas the bleeding score was higher in women (11 [IQR 7–17] vs. 9 [IQR 5–14] ng mL−1 in men, P = 0.002). After adjustment for age and sex by stratification, PAI‐1 level and bleeding score were negatively correlated (Spearman's rho: −0.170, P = 0.017) in the group of 196 young (age ≤ 45 year) female VWD patients, accounting for 31% of our study population. Conclusion In young female VWD patients, we observed that low PAI‐1 levels were associated with a higher bleeding score, which may partly explain the observed variability in bleeding phenotype in VWD patients.</description><identifier>ISSN: 1351-8216</identifier><identifier>EISSN: 1365-2516</identifier><identifier>DOI: 10.1111/hae.13206</identifier><identifier>PMID: 28306198</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adolescent ; Adult ; Age ; Aged ; Aged, 80 and over ; Bleeding ; bleeding score ; Child ; Child, Preschool ; Cohort Studies ; Female ; Fibrinolysis ; Genotype ; Health risk assessment ; Hemorrhage - complications ; Humans ; Infant ; Male ; Middle Aged ; Phenotype ; Plasma levels ; Plasminogen Activator Inhibitor 1 - blood ; Plasminogen Activator Inhibitor 1 - genetics ; Plasminogen activator inhibitors ; plasminogen activator inhibitor‐1 ; Population studies ; von Willebrand disease ; von Willebrand Diseases - blood ; von Willebrand Diseases - complications ; von Willebrand Diseases - genetics ; Von Willebrand factor ; Young Adult</subject><ispartof>Haemophilia : the official journal of the World Federation of Hemophilia, 2017-05, Vol.23 (3), p.437-443</ispartof><rights>2017 John Wiley &amp; Sons Ltd</rights><rights>2017 John Wiley &amp; Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3886-874b82fad92fc60ab778c25058b5d3a9ff873c3d71982c26a673b245803b994e3</citedby><cites>FETCH-LOGICAL-c3886-874b82fad92fc60ab778c25058b5d3a9ff873c3d71982c26a673b245803b994e3</cites><orcidid>0000-0002-2035-4485</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fhae.13206$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fhae.13206$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,786,790,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28306198$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abdul, S.</creatorcontrib><creatorcontrib>Boender, J.</creatorcontrib><creatorcontrib>Malfliet, J. J. M. C.</creatorcontrib><creatorcontrib>Eikenboom, J.</creatorcontrib><creatorcontrib>Fijn van Draat, K.</creatorcontrib><creatorcontrib>Mauser‐Bunschoten, E. P.</creatorcontrib><creatorcontrib>Meijer, K.</creatorcontrib><creatorcontrib>Meris, J.</creatorcontrib><creatorcontrib>Laros‐van Gorkom, B. A. P.</creatorcontrib><creatorcontrib>Bom, J. G.</creatorcontrib><creatorcontrib>Leebeek, F. W. G.</creatorcontrib><creatorcontrib>Rijken, D. C.</creatorcontrib><creatorcontrib>Uitte de Willige, S.</creatorcontrib><creatorcontrib>Fijnvandraat, K</creatorcontrib><creatorcontrib>Coppens, M</creatorcontrib><creatorcontrib>Kors, A</creatorcontrib><creatorcontrib>Jonkers, H</creatorcontrib><creatorcontrib>Boersma, R</creatorcontrib><creatorcontrib>Beckers, A</creatorcontrib><creatorcontrib>Granzen, B</creatorcontrib><creatorcontrib>Tamminga, J</creatorcontrib><creatorcontrib>Linden, W</creatorcontrib><creatorcontrib>Ypma, F</creatorcontrib><creatorcontrib>Smiers, W</creatorcontrib><creatorcontrib>Brons, P</creatorcontrib><creatorcontrib>Nijziel, M</creatorcontrib><creatorcontrib>Cnossen, H</creatorcontrib><creatorcontrib>WIN study group</creatorcontrib><title>Plasma levels of plasminogen activator inhibitor‐1 and bleeding phenotype in patients with von Willebrand disease</title><title>Haemophilia : the official journal of the World Federation of Hemophilia</title><addtitle>Haemophilia</addtitle><description>Introduction von Willebrand disease (VWD) is the most common inherited bleeding disorder. In VWD patients, large variations in bleeding tendency are observed, which cannot be completely explained by the variation in von Willebrand factor levels or activities. Thus, there must be additional factors, for instance, changes in fibrinolysis that have an effect on the variation in bleeding tendency in VWD patients. Aim To investigate whether plasminogen activator inhibitor‐1 (PAI‐1) level influences the variation in bleeding tendency in VWD patients. Methods PAI‐1 antigen levels were measured in the plasma of 633 patients with moderate or severe VWD who participated in the ‘Willebrand in the Netherlands’ (WiN) study, a nationwide multicentre cross‐sectional study. Bleeding severity was assessed using the Tosetto bleeding score. Results PAI‐1 levels increased with age (Spearman's rho: 0.225, P &lt; 0.001) and were higher in men (23 [IQR 12–60] vs. 20 [IQR 10–44] ng mL−1 in women, P = 0.039), whereas the bleeding score was higher in women (11 [IQR 7–17] vs. 9 [IQR 5–14] ng mL−1 in men, P = 0.002). After adjustment for age and sex by stratification, PAI‐1 level and bleeding score were negatively correlated (Spearman's rho: −0.170, P = 0.017) in the group of 196 young (age ≤ 45 year) female VWD patients, accounting for 31% of our study population. Conclusion In young female VWD patients, we observed that low PAI‐1 levels were associated with a higher bleeding score, which may partly explain the observed variability in bleeding phenotype in VWD patients.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Bleeding</subject><subject>bleeding score</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>Fibrinolysis</subject><subject>Genotype</subject><subject>Health risk assessment</subject><subject>Hemorrhage - complications</subject><subject>Humans</subject><subject>Infant</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Phenotype</subject><subject>Plasma levels</subject><subject>Plasminogen Activator Inhibitor 1 - blood</subject><subject>Plasminogen Activator Inhibitor 1 - genetics</subject><subject>Plasminogen activator inhibitors</subject><subject>plasminogen activator inhibitor‐1</subject><subject>Population studies</subject><subject>von Willebrand disease</subject><subject>von Willebrand Diseases - blood</subject><subject>von Willebrand Diseases - complications</subject><subject>von Willebrand Diseases - genetics</subject><subject>Von Willebrand factor</subject><subject>Young Adult</subject><issn>1351-8216</issn><issn>1365-2516</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp10ctKxDAUBuAgiveFLyABN7qo5tKm6VLEGwi6UFyGpD11IpmkNp2R2fkIPqNPYuaiC8FscghffpJzEDqg5JSmdTbScEo5I2INbVMuiowVVKzP64JmklGxhXZifCVkgTbRFpOcCFrJbRQfnI5jjR1MwUUcWtzND6wPL-Cxrgc71UPosfUja2yqvj4-Kda-wcYBNNa_4G4EPgyzDhLCnR4s-CHidzuM8DR4_GydA9PPrzQ2go6whzZa7SLsr_Zd9HR1-Xhxk93dX99enN9lNZdSZLLMjWStbirW1oJoU5ayZgUppCkarqu2lSWveVOmj7CaCS1KblheSMJNVeXAd9HxMrfrw9sE4qDGNtbgnPYQJlFRWUrJ8pKTRI_-0Ncw6X16naIVI7mkMs-TOlmqug8x9tCqrrdj3c8UJWo-CZUmoRZNTvZwlTgxY2h-5U_rEzhbgnfrYPZ_kro5v1xGfgOVDJM1</recordid><startdate>201705</startdate><enddate>201705</enddate><creator>Abdul, S.</creator><creator>Boender, J.</creator><creator>Malfliet, J. 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J. M. C. ; Eikenboom, J. ; Fijn van Draat, K. ; Mauser‐Bunschoten, E. P. ; Meijer, K. ; Meris, J. ; Laros‐van Gorkom, B. A. P. ; Bom, J. G. ; Leebeek, F. W. G. ; Rijken, D. C. ; Uitte de Willige, S. ; Fijnvandraat, K ; Coppens, M ; Kors, A ; Jonkers, H ; Boersma, R ; Beckers, A ; Granzen, B ; Tamminga, J ; Linden, W ; Ypma, F ; Smiers, W ; Brons, P ; Nijziel, M ; Cnossen, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3886-874b82fad92fc60ab778c25058b5d3a9ff873c3d71982c26a673b245803b994e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Bleeding</topic><topic>bleeding score</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Cohort Studies</topic><topic>Female</topic><topic>Fibrinolysis</topic><topic>Genotype</topic><topic>Health risk assessment</topic><topic>Hemorrhage - complications</topic><topic>Humans</topic><topic>Infant</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Phenotype</topic><topic>Plasma levels</topic><topic>Plasminogen Activator Inhibitor 1 - blood</topic><topic>Plasminogen Activator Inhibitor 1 - genetics</topic><topic>Plasminogen activator inhibitors</topic><topic>plasminogen activator inhibitor‐1</topic><topic>Population studies</topic><topic>von Willebrand disease</topic><topic>von Willebrand Diseases - blood</topic><topic>von Willebrand Diseases - complications</topic><topic>von Willebrand Diseases - genetics</topic><topic>Von Willebrand factor</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abdul, S.</creatorcontrib><creatorcontrib>Boender, J.</creatorcontrib><creatorcontrib>Malfliet, J. 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J. M. C.</au><au>Eikenboom, J.</au><au>Fijn van Draat, K.</au><au>Mauser‐Bunschoten, E. P.</au><au>Meijer, K.</au><au>Meris, J.</au><au>Laros‐van Gorkom, B. A. P.</au><au>Bom, J. G.</au><au>Leebeek, F. W. G.</au><au>Rijken, D. C.</au><au>Uitte de Willige, S.</au><au>Fijnvandraat, K</au><au>Coppens, M</au><au>Kors, A</au><au>Jonkers, H</au><au>Boersma, R</au><au>Beckers, A</au><au>Granzen, B</au><au>Tamminga, J</au><au>Linden, W</au><au>Ypma, F</au><au>Smiers, W</au><au>Brons, P</au><au>Nijziel, M</au><au>Cnossen, H</au><aucorp>WIN study group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasma levels of plasminogen activator inhibitor‐1 and bleeding phenotype in patients with von Willebrand disease</atitle><jtitle>Haemophilia : the official journal of the World Federation of Hemophilia</jtitle><addtitle>Haemophilia</addtitle><date>2017-05</date><risdate>2017</risdate><volume>23</volume><issue>3</issue><spage>437</spage><epage>443</epage><pages>437-443</pages><issn>1351-8216</issn><eissn>1365-2516</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Introduction von Willebrand disease (VWD) is the most common inherited bleeding disorder. In VWD patients, large variations in bleeding tendency are observed, which cannot be completely explained by the variation in von Willebrand factor levels or activities. Thus, there must be additional factors, for instance, changes in fibrinolysis that have an effect on the variation in bleeding tendency in VWD patients. Aim To investigate whether plasminogen activator inhibitor‐1 (PAI‐1) level influences the variation in bleeding tendency in VWD patients. Methods PAI‐1 antigen levels were measured in the plasma of 633 patients with moderate or severe VWD who participated in the ‘Willebrand in the Netherlands’ (WiN) study, a nationwide multicentre cross‐sectional study. Bleeding severity was assessed using the Tosetto bleeding score. Results PAI‐1 levels increased with age (Spearman's rho: 0.225, P &lt; 0.001) and were higher in men (23 [IQR 12–60] vs. 20 [IQR 10–44] ng mL−1 in women, P = 0.039), whereas the bleeding score was higher in women (11 [IQR 7–17] vs. 9 [IQR 5–14] ng mL−1 in men, P = 0.002). After adjustment for age and sex by stratification, PAI‐1 level and bleeding score were negatively correlated (Spearman's rho: −0.170, P = 0.017) in the group of 196 young (age ≤ 45 year) female VWD patients, accounting for 31% of our study population. Conclusion In young female VWD patients, we observed that low PAI‐1 levels were associated with a higher bleeding score, which may partly explain the observed variability in bleeding phenotype in VWD patients.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28306198</pmid><doi>10.1111/hae.13206</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-2035-4485</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1351-8216
ispartof Haemophilia : the official journal of the World Federation of Hemophilia, 2017-05, Vol.23 (3), p.437-443
issn 1351-8216
1365-2516
language eng
recordid cdi_proquest_miscellaneous_1878824730
source Wiley
subjects Adolescent
Adult
Age
Aged
Aged, 80 and over
Bleeding
bleeding score
Child
Child, Preschool
Cohort Studies
Female
Fibrinolysis
Genotype
Health risk assessment
Hemorrhage - complications
Humans
Infant
Male
Middle Aged
Phenotype
Plasma levels
Plasminogen Activator Inhibitor 1 - blood
Plasminogen Activator Inhibitor 1 - genetics
Plasminogen activator inhibitors
plasminogen activator inhibitor‐1
Population studies
von Willebrand disease
von Willebrand Diseases - blood
von Willebrand Diseases - complications
von Willebrand Diseases - genetics
Von Willebrand factor
Young Adult
title Plasma levels of plasminogen activator inhibitor‐1 and bleeding phenotype in patients with von Willebrand disease
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