Platelet Biology in Utero-placental Disease
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.
The Rotunda Foundation/ RCSI CLAT scheme
First SupervisorProfessor Fergal Malone
Second SupervisorProfessor Dermot Kenny
CommentsA thesis submitted for the degree of Doctor of Philosophy from the Royal College of Surgeons in Ireland in 2016.
Published CitationMullers SM. Platelet Biology in Utero-placental Disease [PhD Thesis]. Dublin: Royal College of Surgeons in Ireland; 2016.
- Doctor of Philosophy (PhD)