Learn about the symptoms, diagnosis, and groundbreaking treatment that’s changing lives for those with plasminogen deficiency.
By Amy Ehlers, BS, PharmD, BCPS, Senior Clinical Programs Director, Nufactor - February 21, 2025

Plasminogen (PLG) is a naturally occurring protein that is produced in the liver and circulates in the blood. It is the main enzyme responsible for the breakdown of fibrin through the process known as fibrinolysis. Fibrin is the main protein found in blood clots which creates the structure to allow normal tissue to grow and fill in the wound. As healing occurs, fibrinolysis takes place when plasmin cuts the fibrin mesh at various places allowing the fragments to be cleared away.

Plasminogen deficiency (PLGD) is an autosomal recessive disorder due mutation on Chromosome 6. PLGD is considered a rare disease with the incidence estimate at 1.6 people per million worldwide. It is more commonly diagnosed in females and at younger.¹

There are two types of PLGD.

• Type 1 (PLGD1) or hypoplasminogenemia
  • Decreased amount and activity of PLG
• Type 2 (PLGD2) or dysplasminogenemia
  • Normal levels of PLG with decreased activity
  • Usually do not have symptoms and do not treat

PLGD1 symptoms are primarily the development or growth of fibrin-rich woody (ligneous) pseudomembranous lesions on mucous membranes throughout the body. These ligneous lesions are due to excessive fibrin that accumulates, causing inflammation and interfere with tissue and organ function. The lesions are most often seen in the eyes (ligneous conjunctivitis), which can cause vision loss or blindness. The lesions also frequently occur in the mouth (ligneous gingivitis) and can lead to tooth or periodontal bone loss. Other common locations of lesions include respiratory tract, ears, brain, female genital tract, renal system, GI tract and skin.² Diagnosis of PLGD1 is typically based off clinical presentation of ligneous lesions and a plasminogen level of ≤ 45%.

Surgical removal of the lesions is temporary as they will regrow due to decreased plasminogen levels as well as the trauma to the tissue by the surgery. In June 2021, plasminogen, human-tvmh (Ryplazim^®) became the first drug approved for the treatment of patients with PLGD1. Ryplazim^® is plasminogen concentrate purified from human plasma that increases plasminogen levels in the body. As the plasminogen deficiency is corrected, the process of fibrinolysis can naturally occur, and existing lesions lessen and/or resolve. Repeated infusions keep plasminogen levels at a therapeutic level to prevent future ligneous lesion development. Ryplazim^®) is given IV and dosing is based on the patient’s weight. An infusion of Ryplazim^®) may take 15-30 minutes depending on the dose and the frequency of infusions is based on individual response. Patients are taught to self-administer the medication at home to allow for greater independence.

Patient Support Group

• Plasminogen Deficiency Foundation, www.plasminogendeficiency.org

References

1. Congenital Type 1 Plasminogen Deficiency, Accessed January 30, 2025
2. Learn How to Recognize PLGD-1, Accessed January 30, 2025