Complex Changes in von Willebrand Factor-Associated Parameters Are Acquired during Uncomplicated Pregnancy

Autor: Jill M. Johnsen, Hilary S. Gammill, James C. Zimring, Barbara A. Konkle, Gayle Teramura, Dominic W. Chung, Kerry W Lannert, Danielle N. Drury-Stewart
Rok vydání: 2014
Předmět:
Maternal Health
lcsh:Medicine
030204 cardiovascular system & hematology
Biochemistry
0302 clinical medicine
Pregnancy
hemic and lymphatic diseases
Blood plasma
Medicine and Health Sciences
lcsh:Science
Multidisciplinary
biology
Obstetrics and Gynecology
Gestational age
Hematology
Thrombosis
030220 oncology & carcinogenesis
cardiovascular system
Gestation
Female
Coagulation Factors
Research Article
circulatory and respiratory physiology
Adult
congenital
hereditary
and neonatal diseases and abnormalities
medicine.medical_specialty
ADAMTS13 Protein
Adamts13 activity
03 medical and health sciences
Von Willebrand factor
Internal medicine
von Willebrand Factor
medicine
Humans
Blood Coagulation
Uncomplicated pregnancy
Factor VIII
business.industry
lcsh:R
Biology and Life Sciences
Proteins
medicine.disease
ADAM Proteins
Endocrinology
biology.protein
Women's Health
lcsh:Q
Protein Multimerization
business
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 11, p e112935 (2014)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0112935
Popis: 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.
Databáze: OpenAIRE
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