Abstract 37: Tracking Endothelial Injury And Platelet Activation In Childhood Cerebral Arteriopathy

Abstract

Background: Cerebral arteriopathy is a well established risk factor for childhood arterial ischaemic stroke (AIS) recurrence. However, risk stratification of children with AIS and cerebral arteriopathy based on underlying disease mechanisms is currently impossible thus complicating the development of targeted secondary prevention strategies. Objective: We hypothesized that persistent cerebrovascular endothelial injury confers an increased prothrombotic tendency central to the pathogenesis of arteriopathy progression and stroke recurrence. The aim of this single centre cross-sectional study study was to relate indices of endothelial injury and thrombotic propensity to radiological and clinical disease course at least 6 months after the index AIS. Methods: Circulating endothelial cells (CECs) and microparticles (MPs) were identified with immunomagnetic bead extraction and flow cytometry respectively. MP mediated thrombin generation was assessed using a fluorogenic assay. Results were expressed as median and range. Results: 51 children with AIS aged 8•8 (0•9-17•4) years and 20 paediatric controls were included. Eleven were categorised as having progressive disease on clinical and/or radiological grounds while 40 had non-progressive disease. CECs were significantly raised at 120 (66-732) cells /ml in the progressive group, compared to 24 (0-88) cells/ml in the non-progressive group (p = 0•0002) and 32 (0-84) cells/ml in controls (p= 0•0003). In 2/8 children studied prospectively AIS recurrence was associated with increased CECs at 186 (140-232) cells/ml. Total circulating annexin V+ MPs were significantly higher at 553 (136- 1616) x 10 3/ml in then progressive compared to the non-progressive group 227 (49-893) x 10 3/ml, p=0•003. MPs were of endothelial, neutrophil and platelet origin and expressed tissue factor. MP-mediated thrombin generation was enhanced with peak thrombin generation of 127•3 (30-215) nM in the progressive compared to the non-progressive disease group 25 (10-73•40) nM, p=0•0001. Conclusion: We provide important insights into the role of endothelial injury, platelet activation and thrombogenicity in childhood AIS that could for the first time lead to stratified, mechanism specific secondary stroke prevention strategies.