Plasminogen Deficiency

Understanding Plasminogen Deficiency

Plasminogen deficiency (PLGD) is an inherited rare disease in which a mutation on the plasminogen (PLG) gene causes a deficiency in the enzyme plasminogen. Plasminogen plays a role in wound healing. In normal wound healing, fibrin is a protein responsible for forming the framework for tissue regrowth. As tissue fills in the wound area, fibrin is broken down and removed by the body (fibrinolysis). In patients with PLGD, the fibrin is not broken down and instead builds up, forming thick, woody (ligneous) growths.

There are two types of plasminogen deficiency:

1. PLGD1: Type 1 or hypoplasminogenemia is when there is a decrease in both the level and function of plasminogen. Patients with PLGD1 typically require treatment.
2. PLGD2: Type 2 or dysplasminogenemia is when there is a normal or near normal level of plasminogen with decreased activity. Patients with PLGD2 may not have any symptoms and usually do not require treatment.

Symptoms of Plasminogen Deficiency

Patients with PLGD1 develop growths on mucous membranes throughout the body. Mucous membranes include the moist, inner lining of some organs and body cavities (such as the eyes, nose, mouth, lungs, ears, female genital tract, kidney system, gastrointestinal tract, brain) and lubricates and protects these areas from abrasive particles and bodily fluids. The lesions are often inflamed, painful, and can cause damage if left untreated. They may occur spontaneously or be triggered by infection or injury.

Lesions may occur in any mucous membrane of the body. The eyes are the most common site for lesions in patients with PLGD1. Ligneous conjunctivitis (LC) may be seen in to up to 81% of patients. If left untreated, LC may result in vision loss.

Lesions in the mouth, or ligneous gingivitis (LG) are seen in approximately 30% of patients. LG can cause loss of teeth and makes eating and drinking painful.

Patients may experience lesions in one or multiple areas at any given time or lesions may vary throughout their lifetime.

In some cases the lesions may be able to be surgically removed, but this can cause additional lesions to develop due to irritation of the tissue and subsequent wound healing.

Diagnosing Plasminogen Deficiency

Patients with PLGD1 are diagnosed through a detailed patient history and clinical evaluation of pseudomembranous lesions and impaired wound healing. Family medical history is also taken as this is an inherited genetic disorder. A plasminogen activity level is drawn to see if the activity level is ≤ 45%. A plasminogen antigen activity level may also be obtained and may be < 150 ng/L. Molecular genetic testing to evaluate for mutations in the PLG gene and lesion biopsy may also be done but are not required.

Treating Plasminogen Deficiency

Ryplazim^® (plasminogen, human-tvmh) is the only FDA approved therapy for patients with PLGD1. Ryplazim^® is plasma-derived human plasminogen that is infused intravenously. This may be done using a butterfly needle or peripheral IV in the arm or a port in the chest. Ryplazim^® is infused every 2-4 days based on the patient’s response to therapy, but in some cases, infusions may be spaced further. Ryplazim^® can be infused in the home by patients and/or caregivers.

Websites:

• Hypoplasminogenemia – About the Disease – Genetic and Rare Diseases Information Center (nih.gov)
• Rare Coagulation Resource Room | NBDF (bleeding.org)
• Hope for Hemophilia (hopeforhemophilia.org)

Rare Disease and Therapy Registries:

• Get Involved with the Rare Disease Community | NORD (rarediseases.org)

Support Groups:

• Plasminogen Deficiency Foundation

Reference:

• Congenital Type 1 Plasminogen Deficiency – Symptoms, Causes, Treatment | NORD (rarediseases.org)
• Shapiro AD, Menegatti M, Palla R, et al. An international registry of patients with plasminogen deficiency (history). Haematologica. 2020;105:554-61. doi:10.3324/haematol.2019.241158
• Ryplazim^® Package Insert

Last reviewed 12/02/2025