Endothelial Dysfunction in Hematological Patients: Sublingual Microscopy, Hyperspectral Imaging, and Serum Endothelial Markers

Background: EASIX measured before conditioning therapy is a validated marker to predict risk of sepsis and mortality after allogeneic stem cell transplantation (alloSCT) in the context of acute GVHD, and in a variety of malignant and non-malignant conditions outside alloSCT. EASIX has now been reported as a novel marker of mortality of patients with coronary heart disease, with similar effects 2 months before as well as 6 months after cardiac intervention (1). However, the exact relationship of endothelial cell biology with EASIX requires further clarification. Endothelial cell responses to systemic or localized challenges are characterized by functional heterogeneity, therefore no ‘one fits all’ endothelial biomarker has been identified so far. Pre-transplantation markers predict risk of endothelial complications after alloSCT, still, outcome predictions for individual patients remain imprecise. We hypothesize, that the morphological substrate of EASIX is a reduced endothelial glycocalyx thickness resulting in direct interactions of leukocytes and platelets with receptors expressed on endothelial cells, thereby leading to cellular activation (increased LDH), loss of platelets due to activation and microembolism, as well as ensuing kidney damage. The prospective observational EndoCDO-H study (NCT05502887) was designed to compare local and systemic ways of assessing pre-transplant human endothelial function, including sublingual microscopy (Glycocheck®) for assessment of glycocalyx thickness and vessel density, hyperspectral imaging of digits and palms (Tivita®) for assessment of perfusion and tissue water (endothelial leakage), endothelial activation and stress index (EASIX-pre), and serum endothelial markers, in relation to outcome.