Date of Award

Fall 2016

Document type

Thesis

Degree Name

PhD (Doctor of Philosophy)

First Supervisor

Professor Fergal Malone

Second Supervisor

Professor Dermot Kenny

Funder/Sponsor

The Rotunda Foundation/ RCSI CLAT scheme

Keywords

Platelet Function, Platelet Function Assays, Pregnancy, Gestational Hypertension, Pre-Eclampsia, Intrauterine-Growth Restriction

Abstract

The link between platelets and utero-placental disease has been an important research question for the last number of decades. The primary aim of this thesis was to comprehensively investigate platelet biology in utero-placental disease using a number of different platelet function assays, in three clinical entities of utero-placental disease: Gestational Hypertension (GH), Pre-eclampsia (PET) and Intrauterine growth restriction (IUGR). A secondary aim was to correlate platelet function results with clinical outcomes.

For the first assay I found that spontaneous platelet aggregation was reduced in utero-placental disease compared with normal pregnancy controls. The second assay tested was a more comprehensive assay of agonist-induced aggregation and I found that platelet aggregation in response to incremental concentrations of a range of different agonists was also reduced in utero-placental disease compared with normal pregnancy controls. The final assay, the Dynamic Platelet Function Assay (DPFA) measured platelet behaviour over von Willebrand factor (VWF) under arterial shear-flow. I found significant differences in a number of novel platelet parameters in utero-placental disease. I also correlated platelet function with placental histopathology results and identified novel findings of altered platelet biology based on placental histopathology sub-type. I finally investigated differences in DPFA platelet function based on blood group type and found that pregnant patients with blood group O had significantly reduced platelet behaviour on VWF, which could possibly indicate and increased risk of obstetric haemorrhage.

Platelet biology appears to be altered in utero-placental disease, as assessed using three different platelet function assays. The continued development of the final assay, the DPFA, into a point-of-care test may enable more large-scale prospective studies of platelet function in pregnancy as a predictive tool and measure of aspirin response.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

File Size

5.60 MB

Comments

A thesis submitted for the degree of Doctor of Philosophy from the Royal College of Surgeons in Ireland in 2016.

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