Thrombosis Risk in Transgender Adolescents Receiving Gender-Affirming Hormone Therapy.

BACKGROUND AND OBJECTIVES: Many transgender youth experience gender dysphoria, a risk factor for suicide. Gender-affirming hormone therapy (GAHT) ameliorates this risk but may increase the risk for thrombosis, as seen from studies in adults. The aim with this study was to examine thrombosis and thrombosis risk factors among an exclusively adolescent and young adult transgender population. METHODS: This retrospective chart review was conducted at a pediatric hospital-associated transgender health clinic. The primary outcome was incidence of arterial or venous thrombosis during GAHT. Secondary measures included the prevalence of thrombosis risk factors. RESULTS: Among 611 participants, 28.8% were transgender women and 68.1% were transgender men. Median age was 17 years at GAHT initiation. Median follow-up time was 554 and 577 days for estrogen and testosterone users, respectively. Individuals starting GAHT had estradiol and testosterone levels titrated to physiologic normal. Multiple thrombotic risk factors were noted among the cohort, including obesity, tobacco use, and personal and family history of thrombosis. Seventeen youth with risk factors for thrombosis were referred for hematologic evaluation. Five individuals were treated with anticoagulation during GAHT: 2 with a previous thrombosis and 3 for thromboprophylaxis. No participant developed thrombosis while on GAHT. CONCLUSIONS: In this study, we examined thrombosis and thrombosis risk factors in an exclusively adolescent and young adult population of transgender people receiving GAHT. These data suggest that GAHT in youth, titrated within physiologic range, does not carry a significant risk of thrombosis in the short-term, even with the presence of preexisting thrombosis risk factors.

A xenograft model for venous malformation.

Vascular malformations are defects caused by the abnormal growth of the vasculature. Among them, venous malformation (VM) is an anomaly characterized by slow-flow vascular lesions with abnormally shaped veins, typically in sponge-like configuration. VMs can expand over years causing disfigurement, obstruction of vital structures, thrombosis, bleeding, and pain. Treatments have been very limited and primarily based on supportive care, compression garments, sclerotherapy, and/or surgical resection. Sirolimus treatment has recently shown efficacy in some patients with complicated vascular anomalies, including VMs. Activating somatic TIE2 gene mutations have been identified in up to 60% of VMs and PIK3CA mutations have been found in another 25%. Here, we report a xenograft model of VM that reflects the patients' mutation heterogeneity. First, we established a protocol to isolate and expand in culture endothelial cells (VM-EC) from VM tissue or VM blood of nine patients. In these cells, we identified somatic mutations of TIE2, PIK3CA, or a combination of both. Both TIE2 and PIK3CA mutations induced constitutive AKT activation, while TIE2 mutations also showed high MAPK-ERK signaling. Finally, VM-EC implanted into immune-deficient mice generated lesions with ectatic blood-filled channels with scarce smooth muscle cell coverage, similar to patients' VM. This VM xenograft model could be instrumental to test the therapeutic efficacy of Sirolimus in the presence of the different TIE2 or PIK3CA mutations or to test for efficacy of additional compounds in targeting the specific mutated protein(s), thus enabling development of personalized treatment options for VM patients.