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A study of coagulation potential in pre-eclampsia

Tham, Kah Meng (2010) A study of coagulation potential in pre-eclampsia. MSc(R) thesis, University of Glasgow.

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Abstract

Pre-eclampsia is a multisystem obstetric disease of unknown aetiology that is associated with enhanced coagulation, endothelial activation and reduced placental function. A two-stage model for pre-eclampsia has been proposed involving abnormal placentation and the maternal response to this. In this thesis, I have identified a possible relationship between annexin V expressed on the surface of syncytiotrophoblasts and fibrin deposition, suggesting that annexin V may serve to protect the surface of placental villi from excessive coagulation. A prothrombinase assay was developed for the purpose of measuring maternal plasma microparticle procoagulant activity between pre-eclamptic women and healthy pregnant control women. No significant difference was found in microparticle procoagulant activity between these two groups. However, quantitation of fetal Corticotrophin-Releasing Hormone mRNA (CRH mRNA) in maternal plasma as a measure of placental cell debris was undertaken between pre-eclamptic and healthy control groups. There were four-fold higher levels of placental cell debris in the maternal blood of pre-eclamptic patients compared to healthy pregnant controls and the mean fetal CRH mRNA level was greater in the group of pre-eclamptic patients over 36 weeks’ gestation compared to pre-eclamptic patients under 36 weeks’ gestation. Factor VII coagulant activity was also positively correlated with placental cell debris in maternal circulation in pre-eclampsia which suggests that placental cell debris may have procoagulant potential. Measures of coagulation activation, endothelial activation and placental function in maternal plasma were in keeping with the pattern expected for pre-eclamptic patients. Maternal erythrocyte fatty acid status was measured in pre-eclamptic patients and Body Mass Index-matched healthy pregnant controls. Pre-eclamptic patients were found to have a lower percentage of total polyunsaturated fatty acids and total n-6 fatty acids as well as lower amounts of dihomo-γ-linolenic acid, arachidonic acid and docosahexaenoic acid compared to healthy pregnant controls. This change in maternal fatty acid profile would be consistent with a greater synthesis of the potent eicosanoid thromboxane A2. In summary, these results are overall consistent with a state of enhanced coagulation priming in pre-eclampsia.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Keywords: Haemostasis, coagulation, pregnancy, pre-eclampsia, placenta, fetal, intrauterine growth restriction, IUGR, tissue factor, TF, fibrin, annexin V, M30, apoptosis, microparticles, phosphatidylserine, syncytiotrophoblast membrane particles, STBM, corticotrophin-releasing hormone mRNA, CRH mRNA, tissue factor pathway inhibitor, TFPI, thrombin-antithrombin complex, TAT, prothrombin fragment 1+2, factor VIIc, factor XIIa, activated protein C, APC, plasminogen activator inhibitor type 1, PAI-1, soluble intercellular adhesion molecule-1, sICAM-1, soluble vascular cell adhesion molecule-1, sVCAM-1, von willebrand factor, vWF, plasminogen activator inhibitor type-2, PAI-2, thromboxane, prostacyclin, fatty acid, n-3 fatty acids, n-6 fatty acids, polyunsaturated fatty acids, diabetic, immunocytochemistry, ICC, prothrombinase assay, procoagulant activity, coagulation activation, endothelial activation, placental function, erythrocyte membrane fatty acid
Subjects: R Medicine > RG Gynecology and obstetrics
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Freeman, Dr. Dilys
Date of Award: 2010
Depositing User: Dr Kah Meng Tham
Unique ID: glathesis:2010-1916
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 16 Jun 2010
Last Modified: 10 Dec 2012 13:48
URI: http://theses.gla.ac.uk/id/eprint/1916

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