title: Pregnancy outcome and fibrinolytic, endothelial and coagulation markers in women undergoing uterine artery Doppler screening at 23 weeks.
abstract: BACKGROUND
  Pre-eclampsia (PET) and/or fetal growth restriction (FGR) remain a major cause of maternal and fetal morbidity and mortality. In pregnancy, fibrinolysis is controlled by the maternal endothelium and placenta, both of which are central to the pathogenesis of PET/FGR. Clinically, uterine artery Doppler screening at 23 weeks is used to predict PET/FGR. An abnormal uterine artery Doppler finding is defined as early diastolic bilateral uterine artery notching (BN) in the waveform. However, about 50% of mothers with BN do not develop PET/FGR.
  
  
  OBJECTIVE
  We investigated fibrinolytic changes and uterine artery Doppler findings in the second trimester, and related them to pregnancy outcome; in particular assessing whether fibrinolytic markers could discriminate between normal and abnormal outcome in mothers with BN.
  
  
  METHODS
  Plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), plasminogen activator inhibitor-2 (PAI-2), plasmin-alpha(2) antiplasmin (PAP), D-dimers and markers of endothelial dysfunction were measured with Doppler ultrasound at 23 weeks.
  
  
  RESULTS
  Those with BN had decreased PAP and D-dimer levels, and raised PAI-1 and thrombomodulin levels. Mothers with BN and PET/FGR had significantly increased t-PA levels and reduced PAI-2 levels.
  
  
  CONCLUSIONS
  BN at 23 weeks of gestation is associated with increased PAI-1 levels. Within the BN group, mothers who developed PET/FGR had increased t-PA levels and decreased PAI-2 levels, although there was no net change in fibrinolysis as measured by D-dimer levels. No single fibrinolytic marker is helpful in determining pregnancy outcome in those with BN, but t-PA and PAI-2 are worthy of study in a multifactorial algorithm.
authors.affiliation: Thrombosis & Vascular Biology Group, Department of Haematology, Guy's & St Thomas' Trust, London, UK. Beverley.hunt@gstt.nhs.uk
authors.forename: B J
authors.initials: BJ
authors.lastname: Hunt
authors.forename: H
authors.initials: H
authors.lastname: Missfelder-Lobos
authors.forename: M
authors.initials: M
authors.lastname: Parra-Cordero
authors.forename: O
authors.initials: O
authors.lastname: Fletcher
authors.forename: K
authors.initials: K
authors.lastname: Parmar
authors.forename: E
authors.initials: E
authors.lastname: Lefkou
authors.forename: C C
authors.initials: CC
authors.lastname: Lees