A large team at the University of Sydney, including Dr Mike Wu, Imala Alwis and Ethan Italiano have investigated the process leading up to this organ damage and discovered a previously unknown clotting mechanism that occurs in these micro blood vessels. Their findings could lead to possible new ways to treat these serious diseases.
The lack of oxygen and nutrients damages a range of tissues and organs, including the micro blood vessels themselves, causing them to get leaky. The team found that once the endothelial cells that line the blood vessels become damaged, a chain reaction ensues that causes surrounding red blood cells to burst open like balloons. Their sticky remnants then pile up on the damaged endothelial cells, preventing bleeding from the area. However, this process can go too far and the sticky clot can grow big enough to block the micro blood vessels, causing further tissue damage.
The team used multiple human and mouse samples to investigate major human diseases associated with organ damage, including severe COVID-19, heart transplantation and ischemia-reperfusion injury. Extensive multi-modal microscopy techniques at Microscopy Australia’s University of Sydney facility were used to unravel the details of this new clotting mechanism.
Multimodal imaging of micro blood vessels
Their findings also explain why treatments that target only conventional forms of blood clotting are not always successful in treating these diseases, especially later in the process. The additional secondary clotting step could be another pathway that could be targeted with new forms of treatment. The challenge here, would be to strike a balance between blocking up the leaks from the damaged blood vessels without clogging our most vital micro blood vessels.
M.Wu et al. Nature 2025
DOI: 10.1038/s41586-025-09076-x
October 7, 2025
