Nikhil Prasad Fact checked by:Thailand Medical News Team Aug 31, 2026 9 minutes ago
Researchers have uncovered a potentially important mechanism behind the abnormal blood clotting associated with COVID-19, finding unusually high levels of cell-free hemoglobin and iron inside cerebral blood clots removed from stroke patients infected during the pre-Omicron period.
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Cell-Free Hemoglobin and Iron May Drive COVID-19 Stroke Clots
The findings suggest that damage to red blood cells and the subsequent release of hemoglobin, heme, and iron could help create conditions that promote dangerous clot formation.
Researchers Analyze Clots Removed from Stroke Patients
The exploratory study examined cerebral thrombi collected through mechanical thrombectomy from 12 ischemic stroke patients—six with COVID-19 and six non-infected controls. Researchers combined microscopy, immunohistochemistry, quantitative proteomics, and elemental analysis to examine differences in clot structure and molecular composition.
The researchers were affiliated with the General University Hospital of Albacete; Health Research Institute of Castilla-La Mancha (IDISCAM); Hospital Nacional de Parapléjicos; University of Castilla-La Mancha; Instituto de Investigación Sanitaria La Fe; Hospital Universitario y Politécnico La Fe; and University of Valencia, all in Spain.
Hemoglobin and Iron Reveal Striking Signature
In this
Thailand Medical News report, one of the strongest findings came from proteomic analysis. Among 720 proteins shared between COVID-19 and control clots, 48 were significantly different: 28 were increased by more than twofold and 20 were decreased by more than twofold in COVID-19 thrombi.
Hemoglobin alpha, beta, gamma, and delta subunits were markedly increased, alongside haptoglobin, which scavenges free hemoglobin, and biliverdin reductase B, an enzyme involved in heme breakdown. Antioxidant proteins including PRDX2, SOD1, and PRDX4 were also elevated, pointing toward substantial oxidative stress.
Crucially, this was not simply because COVID-19 clots contained more intact red blood cells. Red blood cell content was comparable between groups, while structural erythrocyte proteins were not increased. Elemental analysis simultaneously revealed substantially higher iron concentrations. Together, these findings indicate that much of the excess hemoglobin and iron may have been present outside intact blood cells.
COVID-19 Clots Showed Different Architecture
COVID-19 thrombi also displayed a more disorganized fibrillar structure. Researchers found trends toward more macrophages and less platelet material, while platelet-associated proteins were reduced. Complement components, immunoglobulins, and other inflammatory proteins further indicated a distinctive immune-inflammatory and oxidative environment.
The proposed mechanism is that hemolysis releases cell-free hemoglobin, heme, and ferric iron, which could intensify endothelial dysfunction, complement activity, coagulation, and platelet activation, ultimately encouraging immunothrombosis.
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Conclusions
The findings raise the possibility that previously underrecognized hemoglobin- and iron-related pathways contribute to COVID-19-associated thrombosis and stroke. However, the study included only 12 patients and cannot establish causation, making larger multicenter studies essential before these pathways can be considered validated therapeutic targets.
The study findings were published in the peer reviewed journal: Acta Neuropathologica.
https://link.springer.com/article/10.1007/s00401-026-03074-7
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