Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.

BACKGROUND:The coagulation protein von Willebrand Factor (VWF) is known to be elevated in pregnancy. However, the timing and nature of changes in VWF and associated parameters throughout pregnancy are not well understood. OBJECTIVES:To better understand the changes in VWF provoked by pregnancy, we s...

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Main Authors: Danielle N Drury-Stewart, Kerry W Lannert, Dominic W Chung, Gayle T Teramura, James C Zimring, Barbara A Konkle, Hilary S Gammill, Jill M Johnsen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4237360?pdf=render
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author Danielle N Drury-Stewart
Kerry W Lannert
Dominic W Chung
Gayle T Teramura
James C Zimring
Barbara A Konkle
Hilary S Gammill
Jill M Johnsen
author_facet Danielle N Drury-Stewart
Kerry W Lannert
Dominic W Chung
Gayle T Teramura
James C Zimring
Barbara A Konkle
Hilary S Gammill
Jill M Johnsen
author_sort Danielle N Drury-Stewart
collection DOAJ
description BACKGROUND:The coagulation protein von Willebrand Factor (VWF) is known to be elevated in pregnancy. However, the timing and nature of changes in VWF and associated parameters throughout pregnancy are not well understood. OBJECTIVES:To better understand the changes in VWF provoked by pregnancy, we studied VWF-associated parameters in samples collected over the course of healthy pregnancies. METHODS:We measured VWF antigen (VWF:Ag), VWF propeptide (VWFpp), Factor VIII (FVIII), and ADAMTS13 activity in samples collected from 46 women during pregnancy and at non-pregnant baseline. We also characterized pregnant vs. non-pregnant VWF multimer structure in 21 pregnancies, and performed isoelectric focusing (IEF) of VWF in two pregnancies which had samples from multiple trimesters. RESULTS:VWF:Ag and FVIII levels were significantly increased during pregnancy. ADAMTS13 activity was unchanged. VWFpp levels increased much later in pregnancy than VWF:Ag, resulting in a progressive decrease in VWFpp:Ag ratios. FVIII:VWF ratios also decreased in pregnancy. Most pregnancies exhibited a clear loss of larger VWF multimers and altered VWF triplet structure. Further evidence of acquired VWF qualitative changes in pregnancy was found in progressive, reversible shifts in VWF IEF patterns over gestation. CONCLUSIONS:These data support a new view of pregnancy in which VWF can acquire qualitative changes associated with advancing gestational age. Modeling supports a scenario in which both increased VWF production and doubling of the VWF half-life would account for the data observed. We propose that gestation induces a prolongation in VWF survival, which likely contributes to increased total VWF levels and altered VWF structure.
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spelling doaj.art-b7b6c2bad6c342028a8d73a7495643842022-12-21T18:41:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11293510.1371/journal.pone.0112935Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.Danielle N Drury-StewartKerry W LannertDominic W ChungGayle T TeramuraJames C ZimringBarbara A KonkleHilary S GammillJill M JohnsenBACKGROUND:The coagulation protein von Willebrand Factor (VWF) is known to be elevated in pregnancy. However, the timing and nature of changes in VWF and associated parameters throughout pregnancy are not well understood. OBJECTIVES:To better understand the changes in VWF provoked by pregnancy, we studied VWF-associated parameters in samples collected over the course of healthy pregnancies. METHODS:We measured VWF antigen (VWF:Ag), VWF propeptide (VWFpp), Factor VIII (FVIII), and ADAMTS13 activity in samples collected from 46 women during pregnancy and at non-pregnant baseline. We also characterized pregnant vs. non-pregnant VWF multimer structure in 21 pregnancies, and performed isoelectric focusing (IEF) of VWF in two pregnancies which had samples from multiple trimesters. RESULTS:VWF:Ag and FVIII levels were significantly increased during pregnancy. ADAMTS13 activity was unchanged. VWFpp levels increased much later in pregnancy than VWF:Ag, resulting in a progressive decrease in VWFpp:Ag ratios. FVIII:VWF ratios also decreased in pregnancy. Most pregnancies exhibited a clear loss of larger VWF multimers and altered VWF triplet structure. Further evidence of acquired VWF qualitative changes in pregnancy was found in progressive, reversible shifts in VWF IEF patterns over gestation. CONCLUSIONS:These data support a new view of pregnancy in which VWF can acquire qualitative changes associated with advancing gestational age. Modeling supports a scenario in which both increased VWF production and doubling of the VWF half-life would account for the data observed. We propose that gestation induces a prolongation in VWF survival, which likely contributes to increased total VWF levels and altered VWF structure.http://europepmc.org/articles/PMC4237360?pdf=render
spellingShingle Danielle N Drury-Stewart
Kerry W Lannert
Dominic W Chung
Gayle T Teramura
James C Zimring
Barbara A Konkle
Hilary S Gammill
Jill M Johnsen
Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.
PLoS ONE
title Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.
title_full Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.
title_fullStr Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.
title_full_unstemmed Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.
title_short Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.
title_sort complex changes in von willebrand factor associated parameters are acquired during uncomplicated pregnancy
url http://europepmc.org/articles/PMC4237360?pdf=render
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