Preeclampsia and Contact Activation

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.

Official Title
-----------------
Preeclampsia and Contact Activation

Conditions
-----------------
CAS, Preeclampsia, Misfolding Disease, Protein

Intervention / Treatment
-----------------
* Other: Pregnancy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnant women developing preeclampsia Exclusion Criteria: Healthy pregnant women

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Preeclamptic women<br>Pregnant women who is diagnosed with preeclampsia during anytime of pregnancy. | Other: Pregnancy<br>* Pregnancies complicated by preeclampsia<br>|
| Healthy pregnant women<br>Pregnant women without preeclampsia. Will be matched for body mass index, gestational age and age. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Contact Activation System (CAS) | 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, | 3 years | 
| Misfolded Plasminogen activator inhibitor 2 (PAI-2) | Biomarkers for misfolded PAI-2 in plasma Native PAI-2 antigen, Misfolded PAI-2, Native PAI-1 antigen, | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Contact activation system, PAI-2