Hormone-induced thrombosis is mediated through non-canonical fibrin(ogen) aggregation and a novel estrogen target in zebrafish.

Venous thrombosis is a well-known complication of sex hormone therapy, with onset typically within weeks to months after initiation. Worldwide, more than 100 million pre-menopausal women use combined oral contraceptives, with tens to hundreds of thousands developing thrombosis annually, resulting in significant morbidity and mortality. Although it is known that estrogens can alter expression of coagulation factors, the pathways and mechanisms that connect the two systems, as well as the proteins involved in progression to thrombosis, are poorly understood. Identification of these mediators are central to any comprehensive understanding of hormone-induced pathophysiology, could help ascertain patients at higher risk for thrombosis, and may also pinpoint future therapeutic targets. The zebrafish is a powerful genetic model in which the hemostatic system is almost entirely conserved with humans. Its external development, ability to generate thousands of offspring at low cost, and optical transparency all make it a powerful tool to study the genetics of coagulation disorders. We previously produced a transgenic line (