Preeclampsia and Contact Activation
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 234
- Locations
- 1
- Primary Endpoint
- The Contact Activation System (CAS)
Study Overview
Brief Summary
Preeclampsia (PE) affects approximately 5% of all pregnancies with 2,500 cases registered annually in Denmark. PE is characterized by incomplete modelling of the spiral arteries of the uterus, hypertension, inflammation, hypercoagulability and proteinuria. Neonatal complications and increased cardiovascular risk are common features of the syndrome.
PE shares pathophysiologic features with recognized protein misfolding disorders and misfolded proteins are present in urine from women with PE. Misfolded proteins are potent activators of the contact system (CAS) which is involved in inflammation, coagulation and fibrinolysis.
Plasminogen activator inhibitor 2 (PAI-2) regulates important fibrinolytic processes in the placenta. The oxidative milieu characterizing PE may trigger misfolding of PAI-2 which then loose inhibitory capacity, but gain CAS-activating capacity. Thus, misfolding of PAI-2 may affect the fibrinolytic system in the placenta and compromise the modelling of the spiral arteries. Moreover, misfolded PAI-2 may contribute to the hypercoagulability and the inflammatory conditions characterizing women with PE.
The aim of the present study is i) to characterize CAS in women with PE, ii) to study the CAS-activating capacity of misfolded PAI-2 and iii) to develop and apply immunochemical methods for determination of native and misfolded PAI-2 in plasma.
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Cross Sectional
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Pregnant women developing preeclampsia
Exclusion Criteria
- •Healthy pregnant women
Outcomes
Primary Outcomes
The Contact Activation System (CAS)
Time Frame: 3 years
Biomarkers for the CAS in plasma Coagulation factor XII antigen/activity, High molecular weight kininogen (HK), Truncated (HK), Prekallikrein antigen, kallikrein generation, C1-esterase inhibitor, alpha-2-macroglobulin, Fast form alpha-2-macroglobulin, Thrombin generation,
Misfolded Plasminogen activator inhibitor 2 (PAI-2)
Time Frame: 3 years
Biomarkers for misfolded PAI-2 in plasma Native PAI-2 antigen, Misfolded PAI-2, Native PAI-1 antigen,
Secondary Outcomes
No secondary outcomes reported
Investigators
Anne Cathrine Meldgaard Godtfredsen
Principal investigator, medical doctor, phd student
University of Southern Denmark