Nikhil Prasad Fact checked by:Thailand Medical News Team Sep 20, 2026 50 minutes ago
Scientists investigating why COVID-19 can increase the risk of dangerous blood clots have discovered unusually high levels of cell-free hemoglobin and iron inside cerebral thrombi removed from stroke patients.
COVID-19-associated stroke clots contained unusually high levels of cell-free hemoglobin and iron, revealing
a potential new mechanism contributing to abnormal blood clotting
The findings suggest that some COVID-associated strokes may involve a distinctive combination of blood-cell damage, oxidative stress, inflammation, and abnormal clot formation rather than simply following mechanisms typically associated with ischemic stroke.
Scientists analyzed clots removed from the brain
The Spanish research team studied cerebral thrombi retrieved by mechanical thrombectomy from 12 adults with large-vessel ischemic stroke. Six patients had confirmed COVID-19, while six matched patients without COVID-19 served as controls. COVID-associated clots were collected during the pre-Omicron period of April 2020 to January 2021.
Researchers combined microscopy, immunohistochemistry, elemental analysis, and quantitative proteomics to examine differences in the clots' cellular structure and molecular composition.
Proteomic analysis identified 720 proteins shared between the groups, including 48 that were differentially expressed. COVID-19 thrombi showed marked increases in several hemoglobin subunits, together with haptoglobin, biliverdin reductase, and proteins associated with regulating oxidative stress. Platelet-related proteins were reduced.
Iron and hemoglobin reveal an unusual pattern
Elemental analysis also detected substantially increased iron in COVID-associated thrombi. Four of five assessable COVID clots had iron concentrations exceeding nine sulfur-normalized relative units, compared with just one of five control clots.
Crucially, this was not explained by COVID clots simply containing more intact red blood cells. Glycophorin A staining did not demonstrate increased erythrocyte abundance, while erythrocyte structural proteins were not differentially expressed.
The researchers therefore proposed that much of the excess hemoglobin and iron existed in a cell-free form, potentially reflecting red blood cell damage or hemolysis.
COVID-19 clots also looked structurally different
This
Thailand Medical News report highlights another intriguing finding: COVID-associated clots had a more irregular and less densely organized fibrillar matrix. Electron microscopy revealed a disorganized network lacking the clearer compartmentalized structure seen in control thrombi.
Macrophages also tended to be more abundant, while platelet content was approximately 1.35-fold lower. However, neutrophil abundance and neutrophil extracellular trap levels were not significantly different between groups.
These findings support a possible mechanism in which cell-free hemoglobin and iron contribute to oxidative and
inflammatory processes that favor thrombosis. However, the study was exploratory, involved only 12 patients, and cannot establish that hemolysis directly caused the strokes.
The researchers are affiliated with Spanish institutions including the General University Hospital of Albacete, Health Research Institute of Castilla-La Mancha (IDISCAM), University of Castilla-La Mancha, Hospital Nacional de Parapléjicos, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe, University of Valencia, Príncipe Felipe Research Center, and Universidad Autónoma de Madrid.
Conclusion
The findings reveal a potentially important molecular signature of pre-Omicron COVID-associated stroke, linking cell-free hemoglobin, excess iron, inflammation, oxidative stress, and altered clot architecture. Larger studies are needed to establish whether this mechanism persists with newer SARS-CoV-2 variants and whether it could eventually provide targets for preventing or treating COVID-related thrombosis.
The study findings were published in the peer reviewed journal: Acta Neuropathologica.
https://link.springer.com/article/10.1007/s00401-026-03074-7
Read Also:
https://www.thailandmedical.news/articles/coronavirus
https://www.thailandmedical.news/articles/long-covid
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