Activated neutrophils may trigger potentially fatal hemorrhage associated with some cancer treatments
Immune cells that creep across blood vessels trigger potentially fatal bleeding in platelet-deficient mice, according to a report published in The Journal of Experimental Medicine (2015; doi:10.1084/jem.20142076). If the same is true in humans, blocking the passage of these cells could prevent dangerous complications in patients undergoing transplants or chemotherapy.
Bone marrow transplantation and chemotherapy are known to deplete the blood-clotting cells, resulting in potentially fatal hemorrhage in some patients. Previous studies showed that inflammation was required for bleeding complications to develop in these patients, but exactly what kicks off the process was unknown.
Scientists in Germany have now identified the bloody culprit as the neutrophils. These immune cells are best known as first-responder cells that are called to sites of infection to engulf and destroy invading microbes. But this salutary function is not without consequences, as several microbe-busting products released by activated neutrophils also result in collateral damage to tissue and blood vessels.
When platelet levels are low, the study suggests, the simple act of crawling out of blood vessels is enough for neutrophils to trigger bleeding complications in mice. When they blocked or removed proteins required for neutrophils to traverse the protective endothelial layer of blood vessels, bleeding was prevented. Similarly, in humans, UV-induced skin bleeding was worse in patients with low platelet counts, hinting at the potential therapeutic benefit of blocking neutrophils' cross-vessel journey.
“Specifically targeting neutrophil diapedesis through the endothelial barrier may represent a new therapeutic avenue to prevent fatal bleeding in immune-thrombocytopenic patients,” concluded the authors.