How I treat type 1 plasminogen deficiency

Type 1 plasminogen deficiency (PLGD), an ultrarare disorder caused by PLG pathogenic variants, results in decreased levels of immunoreactive and functional plasminogen. PLGD can cause fibrin-rich pseudomembranes on mucosa that impair tissue/organ function, affect quality of life, and are potentially life threatening. Lesion regression/resolution is facilitated by IV administration of human plasma-derived Glu-plasminogen (IV PLG concentrate), the first and only US Food and Drug Administration-approved specific treatment, licensed in 2021. The diagnosis of PLGD is frequently delayed because of its rarity (1.6 per million) and the variability of the initial medical specialty contact determined by the affected systems. Symptoms are often attributed to more common conditions, such as conjunctivitis, recurrent otitis media, reactive airway disease, etc. This article presents clinical vignettes highlighting strategies for PLGD diagnosis and treatment. Initial evaluation includes a detailed history, laboratory assays, and, at times, radiologic or other procedures. Genetic testing can confirm the diagnosis. Consistent, knowledgeable management is required to promptly identify and treat lesions, even in initially asymptomatic individuals. Personalized treatment may include continuous prophylaxis or intermittent treatment with IV PLG concentrate, dependent on disease severity and clinical course. Specialized facilities such as hemophilia treatment centers offering multidisciplinary care represent medical homes for this ultrarare disorder.