In June 2021, the FDA approved Ryplazim, the first-ever treatment for patients with plasminogen deficiency. This medication is plasminogen, purified from human plasma, that is given as an infusion into the bloodstream. Ryplazim was found to be safe and effective in a clinical trial of 15 adult and pediatric patients with plasminogen deficiency (ref 4), and represents a major advancement in the treatment of this rare disorder. It should be considered the first-line treatment for patients with plasminogen deficiency. The approval of Ryplazim will dramatically change the experience of living with PLGD for the better.
Investigational plasma-derived plasminogen concentrate has also shown clinical success when formulated as ophthalmologic drops (ref 3). The patients in this study have generally shown excellent clinical progress, resolution of nearly all ophthalmologic lesions and return to normal organ function, and very low rates of side effects. The ophthalmologic concentrate is not yet commercially available, but once accessible by all patients, will be another safe and effective treatment option for PLGD patients.
Surgical removal of lesions usually results in regrowth which can be rapid without appropriate medical therapy, and can contribute to long-term scarring and organ damage. Patients should minimize any surgical procedures, including surgical membrane removal, unless lesions become life threatening. Even then, surgical procedures should be done under the guidance of a physician who is knowledgeable about plasminogen deficiency (see Patient Resources for a list of recommended PLGD treatment centers).
Prior to the approval of Ryplazim, many non-specific treatments have been reported in case studies and series; however, these treatment options have inconsistent efficacy and do not address the underlying deficiency state. Fresh frozen plasma (FFP) has been reported to have success in some cases when used systemically (injected into the veins) (ref 1) or when prepared as eye drops or given as an injection into the subconjunctival area (ref 2). FFP has a low concentration of plasminogen and often must be given repeatedly over a period of time to increase the plasminogen activity level and improve symptoms. Additional complications of FFP administered intravenously can include allergic reactions to other proteins in the FFP, or volume overload with difficulty breathing, and in rare cases, heart pumping issues.
- Kizilocak et. al. Treatment of plasminogen deficiency patients with fresh frozen plasma. Pediatr Blood Cancer. 2018;65(2):e26779.
- Tabbara. Prevention of ligneous conjunctivitis by topical and subconjunctival fresh frozen plasma. Am J Ophthalmol. 2004; 138 (2):299-300.
- Nakar et. al. Safety & efficacy of human plasma derived plasminogen ophthalmic drops for treatment of ligneous conjunctivitis: report of phase 2/3 clinical trial. Blood. 2015;126(23):2288.
- Shapiro et. al. Plasminogen replacement therapy for the treatment of children and adults with congenital plasminogen deficiency. Blood. 2018;131(12):1301-1310.