Poster Presentation Australia and New Zealand Society for Extracellular Vesicles Conference 2023

Age-related changes in coagulation and extracellular particles: a pilot study (#68)

Caroline Reddel 1 , Gabrielle Pennings 1 , Vivien Chen 1 2 , Sonali Gnanenthiran 1 3 , Leonard Kritharides 1 3
  1. ANZAC Research Institute, CONCORD, NEW SOUTH WALES, Australia
  2. Department of Haematology, Concord Repatriation General Hospital, Concord, NSW, Australia
  3. Department of Cardiology, Concord Repatriation General Hospital, Concord, NSW, Australia

Aims. The haemostatic system becomes unbalanced with ageing, with increased incidence of both thrombotic events and bleeding. Laboratory assays suggest older people are more prone to clotting (hypercoagulable) and have less capacity for fibrinolysis, but many clinical studies exclude participants >70y. We aimed to identify dynamic changes in coagulation with healthy ageing and any association with phosphatidylserine-positive cell-specific extracellular particles (EP).

Methods. Citrated platelet-free plasma was collected from healthy older (age ≥70y, n=28) and young (20-30y, n=20) community-dwelling people in this pilot study. Plasma was used to test dynamic coagulation and fibrinolysis using the Overall Haemostatic Potential (OHP) assay and circulating EP using flow cytometry after staining for phosphatidylserine (PS) and platelet, endothelial and leukocyte markers. Groups were compared with Mann-Whitney U tests and associations between markers identified using Spearman correlations. Results are median [confidence interval].

Results. The OHP assay identified a hypercoagulable and hypofibrinolytic state in the older cohort, with faster and more extensive fibrin generation and slower fibrinolysis (overall fibrinolytic potential 20-30y: 75 [71-76]%, ≥70y: 64 [60-70]%, p=0.002). Some leukocyte-derived EP correlated with coagulation/fibrinolysis (e.g. PS+/CD11b+ associated with velocity of fibrin generation, Spearman ρ=0.408, p=0.048, n=24) but there were no differences between old and young cohorts in any EP population.

Conclusions. The OHP assay confirms a hypercoagulable and hypofibrinolytic profile in healthy elderly people, with no apparent age-related link to cell-specific extracellular particle populations. These findings support the development of age-specific normal ranges for coagulation studies and future studies testing links between these parameters and clinical risk factors.