Characterization of Platelet Activation in Patients with Eisenmenger Syndrome
Authors: Haire Gordon , Egan Karl , Kevane Barry , Fay Michael , Fortune Anne , Savage Rhona , Doran Esther , O'Neill Ciara , Walsh Kevin , Kenny Damien , Lennon Aine , Maguire Patricia , Ni Ainle Fionnuala 
Published: October 2019

Abstract

Background
Eisenmenger Syndrome (ES) is an extremely rare and serious complication of congenital heart disease in which pulmonary vascular resistance overcomes that of the systemic circulation causing bidirectional or reversed flow across an intracardiac shunt. Patients with ES have an increased incidence of both thrombotic and bleeding complications which occur through poorly understood mechanisms. We have recently demonstrated a critical mechanistic role for platelets in supporting abnormal hypercoagulability in patients with ES using calibrated automated thrombography (Kevane & Ní Áinle et al., J Thromb Haemost 2018).
Aims
Based upon our published data, we further hypothesized that patients with ES would have higher plasma concentrations of platelet activation markers. Therefore, the aim of this study was to measure plamsa levels of soluble P-Selectin (sP-Selectin) and soluble glycoprotein VI (sGPVI) in patients with ES and in matched healthy controls.
Methods
Patients over the age of 18 with Eisenmenger Syndrome and healthy controls were recruited from the cardiology service at a large tertiary referral centre (Mater Misericordiae University Hospital) incorporating the Irish national congenital heart disease service. Platelet poor plasma (PPP) was generated from participants' blood by centrifugation at 2000xg for 10 minutes at room temperature. Commercially available ELISA assays employing quantitative sandwich immunoassay techniques were performed according to manufacturer protocol to measure plasma sP-Selectin and sGPVI levels. All experiments were performed in duplicate with results expressed as mean +/- standard error of mean. Comparisons between groups were made utilising the Student's t-test with a p-value < 0.05 deemed to represent statistical significance.
Results
During the study period, >14,000 patients attended the MMUH cardiology service. Of these, 14 consecutive patients with a diagnosis of ES and 10 matched healthy controls were recruited. Patients with ES had significantly elevated plasma concentrations of both soluble P-Selectin [38.5 +/- 8.3 vs. 11.3 +/- 4.2 ng/ml (p < 0.05)] and soluble GPVI [10.5 +/- 2.4 vs. 1.5 +/- 1.4 ng/ml (p < 0.01)] compared to healthy controls.
Conclusion
Building upon our recently published data in this population, a large cohort given the extreme rarity of this condition, increased concentrations of markers of platelet activation in individuals with ES further suggest a mechanistic role for platelets in ES-mediated hypercoagulability. This phenotype may be a consequence of vascular pathology associated with pulmonary hypertension in these patients. As such, therapies targeted at underlying vascular pathologies may act to ameliorate prothrombotic tendencies and we aim to characterize response to therapy during this ongoing study.

Disclosures
Ni Ainle: Leo Pharma: Research Funding; Actelion: Research Funding; Bayer: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Boehringer: Membership on an entity's Board of Directors or advisory committees.