Significance Abdominal aortic aneurysm (AAA) is a disease of the abdominal aorta where inflammation causes damage and can ultimately lead to rupture. When this happens, uncontrolled internal bleeding can lead to death within minutes. Many aneurysms are not detected until they rupture, and for those that are, treatments to stop them progressing are limited. Here we used biophysics and genetically modified mice to show that a new family of lipids (fats) made by circulating blood cells promote AAA formation in the vessel wall because they directly regulate blood clotting. An approach that prevents AAA development was identified, based on intravenous administration of lipids. The studies provide insights into how AAA develops and may lead to novel therapies for this disease.