Brian Cotter

Platelet function in patients with a history of unexplained recurrent miscarriage who subsequently miscarry again.

OBJECTIVE This study was designed to evaluate platelet aggregation in pregnant women with a history of unexplained recurrent miscarriage (RM) and to compare platelet function in such patients who go on to have either another subsequent miscarriage or a successful pregnancy. STUDY DESIGN A prospective longitudinal study was performed to evaluate platelet function in a cohort of patients with a history of unexplained RM. Platelet reactivity testing was performed at 4-7 weeks gestation, to compare platelet aggregation between those with a subsequent miscarriage and those who had successful live birth outcomes. Platelet aggregation was calculated using a modified assay of light transmission aggregometry with multiple agonists at different concentrations. RESULTS In a cohort of 39 patients with a history of RM, 30 had a successful pregnancy outcome while nine had a subsequent miscarriage again. Women with subsequent miscarriage had reduced platelet aggregation in response to adenosine diphosphate (P value 0.0012) and thrombin receptor activating peptide (P value 0.0334) when compared to those with successful pregnancies. Women with subsequent miscarriages also had a trend towards reduced platelet aggregation in response to epinephrine (P value 0.0568). CONCLUSION Patients with a background history of unexplained RM demonstrate reduced platelet function if they have a subsequent miscarriage compared to those who go on to have a successful pregnancy.

Reduced spontaneous platelet aggregation: a novel risk factor for adverse pregnancy outcome

OBJECTIVE Spontaneous platelet aggregation has not been adequately assessed as a potential risk factor for adverse outcomes in pregnancy. Therefore the objective of this study was to assess spontaneous platelet aggregation (SPA), measured via a novel functional assay, as a risk factor for hypertensive disease and intra-uterine growth restriction (IUGR). STUDY DESIGN This was a prospective longitudinal study. Spontaneous platelet aggregation was assessed as a marker of platelet reactivity using a modification of light transmission aggregometry. Platelet reactivity was assessed in four groups: non-pregnant healthy female volunteers (n=30), longitudinally in normal uncomplicated pregnancy (n=50), hypertensive disorder (n=40) and IUGR (n=30). The mean percentage SPA was plotted and compared across all groups. RESULTS Spontaneous platelet aggregation was significantly reduced in the first trimester compared to the non-pregnant group (p-value=0.003). The mean aggregation for the hypertensive group was 1.9%, (95% CI -0.08 to 4.02) and for the IUGR group was 1.6%, (95% CI -0.6 to 3.72). Platelet aggregation in the hypertensive group was significantly reduced compared to the normal pregnant group (p<0.05). Spontaneous platelet aggregation was also reduced in the IUGR group compared to normal pregnancy (p<0.05). CONCLUSION This study demonstrates that a reduction of spontaneous platelet aggregation may be a novel risk factor for adverse pregnancy outcomes such as pre-eclampsia and IUGR. The most clinically significant finding is that SPA is significantly lower in pregnancies complicated by hypertension and IUGR compared to those who had a normal pregnancy outcome. Further studies should be carried out to asses if spontaneous platelet aggregation may be a clinically useful tool for the prediction of pre-eclampsia and IUGR.

PF.04 Abnormal Platelet Reactivity in Pregnancies Complicated by Intrauterine Growth Restriction

Platelet function in pregnancies complicated by intra-uterine growth restriction (IUGR) is not well understood. We sought to evaluate platelet function in response to multiple concentrations of multiple agonists in pregnancies complicated by IUGR using a novel platelet function assay. Cases of intrauterine growth restricted singleton pregnancies were recruited following ultrasound diagnosis between 24–40 weeks gestation (estimated fetal weight <10th centile for gestational age) in a tertiary referral centre. A modification of standard light transmission aggregometry was used to assess platelet reactivity. Several agonists were assessed at incremental concentrations to characterise the response to multiple receptors. The findings were compared to healthy controls matched for gestational age with normal fetal weight. A total of 24 pregnancies complicated with IUGR and 36 healthy controls were recruited. Platelet reactivity in response to the agonists Arachidonic acid, Adenosine-diphosphate, Epinephrine and Thrombin-receptor activating protein was significantly reduced in the IUGR cohort. There was a nonsignificant trend to decreased reactivity in response to collagen (Table 1). Abstract PF.04 Table 1 Concentration of EC50 for each agonist Agonist EC50 P value Normal pregnancy IUGR Arachidonic acid 0.064 0.283 <0.0001 Adenosine-diphosphate 21 54 0.0007 Collagen 0.052 0.427 0.0973 Epinephrine 231.4 3839 0.0015 Thrombin-receptor activating protein 10.27 71.54 <0.0001 In pregnancies complicated by IUGR there is a significant decrease in platelet function compared to healthy pregnant controls. This may reveal valuable insights into the patho-physiology of the disease, and may represent an inadequate growth factor response in IUGR. Further evaluation of the role of platelets may and aid in the development of future interventions for IUGR.

PF.11 Abnormal Platelet Function is Seen in Women with Unexplained Recurrent Miscarriage During Pregnancy

Objective To evaluate platelet aggregation in patients with a history of recurrent miscarriage (RM) during a subsequent successful pregnancy and compare them to healthy pregnant controls. Study design A prospective longitudinal study was performed to compare platelet function in 30 patients with a history of three consecutive unexplained first trimester pregnancy losses and 30 healthy age-matched pregnant controls. Exclusion criteria included the use of anti-platelet medications such as aspirin and medical conditions that can affect platelet function. Light transmission aggregometry was used to assay platelet agonists at different times and concentrations to create dose-response curves. Results In contrast, to the increased platelet aggregation response seen in healthy controls, platelet reactivity in patients with RM peaked at 12–14 weeks gestation, highlighted by the increased aggregation response to epinephrine (p = 0.0008) and collagen (p < 0.0001) and then decreased in the third trimester in response to epinephrine (p < 0.0001), arachidonic acid (p < 0.0001) and Thrombin Receptor Activating Peptide (p < 0.0001). Conclusion Patients with a history of recurrent miscarriage have significantly different platelet function when compared to healthy controls, in particular during the first trimester. Knowledge of which patients have impaired platelet function may allow for more targeted therapy in the setting of recurrent miscarriage.

PP.36 The Impact of Unexplained Recurrent Miscarriage on Subsequent Pregnancy Outcomes

Aim We sought to determine subsequent pregnancy outcomes in a cohort of women with a history of unexplained recurrent miscarriage (RM) as compared to healthy pregnancy controls. Study design This was a prospective cohort study of women attending a dedicated RM clinic in the Rotunda Hospital in 2011. Inclusion criteria included women with a history of three consecutive first trimester losses that were unexplained in the past, no medical intervention and singleton pregnancies only. The inclusion criteria for the healthy controls included no history of stillbirth, intrauterine growth restriction, preeclampsia or preterm labour. Results Of the 42 women with RM recruited to the study nine (23%) experienced further first trimester miscarriages, one molar and one ectopic pregnancy. The remaining RM cohort with ongoing pregnancies (n = 31) were compared to healthy controls (n = 31) matched for age and BMI. The only statistical difference between the two groups was the earlier mean gestational delivery of the RM group (38 + 2 vs 39 + 4 weeks, p = 0.004) attributed to earlier induction due to their past history. Otherwise there was no significant difference with respect to pregnancy complications, delivery and neonatal outcomes. All of RM patients achieved successful term deliveries with a 74% vaginal delivery rate and a mean birthweight of 3.23 kg. Conclusion This study re-iterates the reassuring prognosis for women with a history of unexplained RM who undergo supportive care at a dedicated clinic. The majority delivered appropriately grown fetuses at term which was comparable to healthy controls.