Abstract Background and aims The introduction of mechanical thrombectomy has markedly improved outcomes for patients with large vessel occlusion stroke. Yet, despite successful macrovascular reperfusion, 40–50% of patients remain severely disabled. One proposed cause is persistent microvascular obstruction or “reperfusion failure”, defined as inadequate tissue-level perfusion despite vessel recanalization, possibly driven by activated neutrophils and micrometer-sized blood clots. There is therefore an urgent need to identify patients at risk of poor recovery and stroke recurrence. The CLOTSAFE study (NCT06530927) aims to characterize morphological alterations in neutrophils and the composition of microclots in stroke patients as potential blood-based biomarkers of a prothrombogenic state and predictors of reperfusion failure. We further seek to explore their association with stroke risk and underlying etiology. Methods Our ongoing prospective observational study aims to include 500 patients with acute and chronic ischemic stroke, together with a control group of individuals exhibiting various stroke risk factors. Label-free digital holo-tomographic microscopy (DHTM) is used to analyze the morphology of altered neutrophil phenotypes and microclot composition in peripheral blood samples. Quantitative, morphological characteristics such as the size and overall shape of microclots and neutrophils will be correlated with clinical outcomes, including reperfusion failure, stroke recurrence, and functional recovery. Results Preliminary findings demonstrate that DHTM can precisely detect neutrophil morphological alterations and characterize microclot composition in plasma samples in a non-invasive manner. We hypothesize that structural characteristics of neutrophils and microclots, as well as the influence of neutrophil extracellular traps (NETs), may provide valuable insights into the risk of reperfusion failure and overall stroke outcome. Conflict of interest Talia Bergaglio: nothing to disclose. Lukas Otto: nothing to disclose. Simone Huber: nothing to disclose. Hannah-Lea Handelsmann: nothing to disclose. Hakim Baazaoui: nothing to disclose. Peter Nirmalraj: nothing to disclose. Susanne Wegener: nothing to disclose. Figure 1 - belongs to Results
Bergaglio et al. (2026) studied this question.