Genital Involvement in Female Patients With Congenital Type 1 Plasminogen Deficiency: A Case Series and Updated Literature Review

INTRODUCTION: Congenital type 1 plasminogen deficiency (PLGD1) is an ultra-rare disorder characterized by the formation of fibrin-rich pseudomembranes on mucosal surfaces across multiple organ systems. In affected females, ligneous lesions may involve the genital tract. AIM: We aimed to characterize the clinical manifestations and therapeutic approaches associated with genital involvement in females with PLGD1. METHODS: A structured literature review was performed to identify previously reported females with PLGD1 and genital lesions. In addition, PLGD1 patients followed at Padua University Hospital were included. RESULTS: A total of 57 females with genital manifestations consistent with PLGD1 were identified, including 4 cases from our institution, 8 patients enrolled in a phase 2-3 clinical trial, and 9 cases described before recognition of the association with plasminogen deficiency. Reported plasminogen activity levels ranged from < 2% to 50%. Pseudomembranous lesions involved the vagina, cervix, endometrium, ovaries, and fallopian tubes. Genital involvement represented the sole clinical manifestation in 13 of 57 patients (22.8%). The most common symptoms included dysmenorrhea, vaginal discharge, post-coital bleeding, and infertility (18/38 cases, 47.4%). Surgical excision was associated with a high rate of recurrence. Data on topical and systemic treatments for genital involvement were limited and largely empirical. The most effective therapeutic approach was replacement therapy with human Glu-plasminogen concentrate and fresh frozen plasma. CONCLUSIONS: Genital tract involvement in PLGD1 is not uncommon and may represent the sole manifestation of the disease, with potential implications for fertility. Glu-plasminogen replacement therapy has shown promising results, although its availability remains limited worldwide.