739: Abnormalities in platelet reactivity in preeclampsia

Abstract

Aoife Murray, Naomi Burke, Karen Flood, Brian Cotter, Zara Fonseca-Kelly, Mark Hehir, Mark Dempsey, Louise Fay, Jennifer Catherine Donnelly, Patrick Dicker, Michael Geary, Dermot Kenny, Fergal Malone Royal College of Surgeons in Ireland, Obstetrics and Gynecology, Dublin 1, Ireland, Rotunda Hospital, Obstetrics and Gynecology, Dublin 1, Ireland, National Maternity Hospital, Obstetrics and Gynaecology, Dublin, Ireland, Royal College Of Surgeons in Ireland, Epidemiology and Public Health, Dublin, Ireland, Rotunda Hospital, Obstetrics and Gynaecology, Dublin, Ireland, Clinical Research Centre, Royal College of Surgeons in Ireland, Dublin 2, Ireland, Royal College of Surgeons in Ireland, Obstetrics and Gynaecology, Dublin, Ireland OBJECTIVE: To determine abnormalities in reactivity of platelets in cases of pre-eclampsia and gestational hypertension using a novel platelet function assay. STUDY DESIGN: Thirty patients diagnosed with either pre-eclamspia or gestational hypertension were recruited. Inclusion criteria were singleton pregnancies between 24 0 and 39 6 with either pre-eclampsia or gestational hypertension as defined by ACOG criteria. Exclusion criteria included diabetes, clotting disorders, aspirin usage or BMI 30. All patients were in the third trimester of pregnancy and the values obtained were compared to patients (N 30) who were in the third trimester of uncomplicated normal pregnancy not affected by either pre-eclamspia or gestational hypertension. A 30ml whole blood sample was drawn according to a strict protocol to maintain platelet integrity. A platelet function assay was performed on each sample within 30 minutes of blood draw. A modification of standard light transmission aggregometry was used to assess platelet function, with light absorbance measured following addition of 5 different agonists at maximal and sub-maximal concentrations. Since platelets have multiple receptors it is necessary to study more than one receptor with the various agonists. The percentage aggregation response for each concentration of each agonist was calculated. RESULTS: Platelet reactivity differed significantly between the two groups of patients for each agonist. Platelet aggregation to arachidonic acid (p 0.0042), epinephrine (p 0.00001) and collagen (p 0.00001) was less reactive in pre-eclamptic and gestational hypertension than in uncomplicated third trimester patients. This pattern of platelet aggregation was not repeated for the agonists TRAP and ADP. CONCLUSION: We have demonstrated a significant reduction in platelet reactivity in patients with both pre-eclampsia and gestational hypertension compared to patients with uncomplicated pregnancies in the third trimester. These data may be of value when designing interventions for prevention or treatment of pre-eclampsia. 740 Effect of postnatal angiotensin-converting enzyme inhibition on fetal vascular programming in a transgenic mouse model lacking endothelial nitric oxide synthase Arshag Kalanderian, Giuseppe Chiossi, Maged Costantine, Phyllis Orise, Gary D.V. Hankins, George R. Saade, Monica Longo The University of Texas Medical Branch, Obstetrics & Gynecology, Galveston, TX OBJECTIVE: Angiotensin converting-enzyme (ACE) inhibitors have been used in adults to prevent progression of hypertension and altered vascular remodeling. We have previously shown that heterozygous offspring developing in an adverse uterine environment lacking endothelial nitric oxide synthase (NOS3) have altered vascular function, and develop hypertension later in life. Our objective was to determine whether captopril, an ACE inhibitor, prevents the fetal programming of adult vascular function in this murine model. STUDY DESIGN: Homozygous NOS3 knockout (KO) and wild type (WT) mice were cross-bred to produce heterozygous offspring developing in a WT mother with a normal uterine environment (KOP) versus a KO mother lacking a functional NOS3 (KOM). Osmotic minipumps were placed in female offspring at 4 weeks of age to deliver captopril or vehicle at 0.25 l/hr for 4 weeks. At 14 weeks, the offspring were sacrificed, and carotid arteries were isolated for in vitro vascular reactivity studies. Contractile responses to phenylephrine (PE), in the presence and absence of the nitric oxide synthase inhibitor L-NAME, and angiotensin (ANG), as well as vasorelaxant responses to acetylcholine (Ach) and isoproterenol (ISO) were determined. ANOVA followed by Neuman-Keuls post hoc test were used for statistical analysis (significance: P 0.05). RESULTS: Contractile responses to PE were significantly increased in KOM offspring compared with KOP, and treatment with captopril corrected this response without any effect on responses in KOP (Figure A). The difference between KOM-CAP vs KOM was decreased by L-NAME, although the response in KOM remained higher. No significant differences were seen in response to ANG between the groups. Vasorelaxant responses to Ach (Figure B) and ISO were significantly improved in KOM treated with captopril compared to untreated KOM offspring (p 0.05). CONCLUSION: Treatment with an ACE inhibitor at a young age prevents the vascular dysfunction seen with fetal programming of adult hypertension. ACE inhibition may represent a potential strategy for postnatal prevention of adult hypertension. Poster Session V Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical-Disease www.AJOG.org