title: Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Research Institute, Puget Sound Blood Center, Seattle, Washington, United States of America.
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Drury-Stewart
authors.affiliation: Research Institute, Puget Sound Blood Center, Seattle, Washington, United States of America.
authors.forename: Kerry W
authors.initials: KW
authors.lastname: Lannert
authors.affiliation: Research Institute, Puget Sound Blood Center, Seattle, Washington, United States of America.
authors.forename: Dominic W
authors.initials: DW
authors.lastname: Chung
authors.affiliation: Research Institute, Puget Sound Blood Center, Seattle, Washington, United States of America.
authors.forename: Gayle T
authors.initials: GT
authors.lastname: Teramura
authors.affiliation: Research Institute, Puget Sound Blood Center, Seattle, Washington, United States of America; Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: James C
authors.initials: JC
authors.lastname: Zimring
authors.affiliation: Research Institute, Puget Sound Blood Center, Seattle, Washington, United States of America; Department of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Konkle
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington, United States of America; Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Hilary S
authors.initials: HS
authors.lastname: Gammill
authors.affiliation: Research Institute, Puget Sound Blood Center, Seattle, Washington, United States of America; Department of Medicine, University of Washington, Seattle, Washington, United States of America.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Johnsen
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000071120:ADAMTS13 Protein; D000328:Adult; D005169:Factor VIII / Q000378:metabolism*; D005260:Female; D006801:Humans; D011247:Pregnancy / Q000097:blood / Q000378:metabolism*; D055503:Protein Multimerization; D014841:von Willebrand Factor / Q000737:chemistry / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor; D005169:Factor VIII; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human