Diagnosis

A variety of conditions, resulting from the deficiency of plasminogen, necessitate multi-disciplinary, coordinated care for these patients.

Patients’ wound-healing capability is severely reduced and is often obvious in mucous membranes (e.g., conjunctivae) where plasminogen plays a crucial role in intravascular and extravascular fibrinolysis.1

Ligneous conjunctivitis, characterized by thick, woody (ligneous) growths on the conjunctiva of the eye (Figure 2), is the main manifestation (80% of cases) of hypoplasminogenemia (type I). It first appears with erythema of the conjunctivae and chronic tearing followed by the formation of pseudomembranes (yellow-white or thick red masses with a wood-like consistency) on the palpebral surfaces. Pseudomembrane development is often the result of mechanical injury to the conjunctival mucosa relating to infection, trauma, or surgery. If left untreated,

ligneous conjunctivitis can lead to blindness. Most affected cases are infants and children with plasminogen deficiency showing their first clinical manifestation at a median age of approximately 10 months.2, 3

Figure 2: Ligneous Conjunctivitis
Ligneous Conjunctivitis

The mucosa of mouth, ears, gastrointestinal tract, respiratory tract, and female genital tract may also be involved, leading to local complications.4

References:

1. Mehta R, Shapiro AD. Plasminogen activator inhibitor type I deficiency. Haemophilia. 2008;14:1255-1260.

2. Shuster V, Hügle B, Tefs K. Plasminogen deficiency. J Thromb Haemost. 2007;5(12):2315-2322.

3. Bateman J B, Pettit T H, Isenberg S J, Simons KB. Ligneous conjunctivitis: an autosomal recessive disorder. J Pediatr Ophthalmol Strabismus. 1986;23:137-140.

4. Pergantou H, Likaki D, Fotopoulou M, Katsarou O, Xafaki P, Platokouki H. Management of ligneous conjunctivitis in a child with plasminogen deficiency. Eur J Pediatr. 2011;170:1333-1336.

If you are interested in participating (or know of a patient who may be interested) in the clinical trial, please register, and a representative from Prometic will contact you.

Testing

In patients with lesions suspected to be ligneous, a plasminogen antigen and activity level should be obtained.

As the majority of clinical lesions have been associated with type I deficiency, it is important to evaluate both assays to demonstrate a decreased plasminogen activity with concordant decrease in protein level. Plasminogen activity is measured with a chromogenic assay with a general normal range of 70-130%, while antigenic testing is commonly performed via immunologic assays with a normal reported range of approximately 6-25mg/dL.1 By the age of 1 year, plasminogen levels have reached a stable level, and do not vary with age.1

References:

1. Mehta R, Shapiro AD. Plasminogen deficiency laboratory evaluation. Rare Coagulation Disorders.www.rarecoagulationdisorders.org/diseases/plasminogen-deficiency/laboratory-evaluation Accessed October 30, 2015.

Prognosis

The prognosis of hypoplasminogenemia is variable depending on the extent, location(s), length, and site of the lesions.

A number of patients have died or have loss of affected organ function, such as sight and dentition, as a result of hypoplasminogenemia.1 The one clearly documented effective therapy that leads to resolution and halts re-formation of ophthalmologic lesions is systemic or topical PLG concentrates.2, 3, 4, 5

A systemic PLG replacement therapy using GLU-Plasminogen is currently under clinical investigation with patients receiving infusions twice weekly.

References:

1. Mehta R, Shapiro AD. Plasminogen activator inhibitor type I deficiency. Haemophilia. 2008;14:1255-1260.

2. Heidemann DG, Williams GA, Hartzer M, Ohanian A, Citron ME. Treatment of ligneous conjunctivitis with topical plasmin and topical plasminogen. Cornea. 2003;22:760–762.

3. Watts P, Suresh P, Mezer E, et al. Effective treatment of ligneous conjunctivitis with topical plasminogen. Am J Ophthalmol. 2002;133:451–455.

4. Pergantou H, Likaki D, Fotopoulou M, Katsarou O, Xafaki P, Platokouki H. Management of ligneous conjunctivitis in a child with plasminogen deficiency. Eur J Pediatr. 2011;170:1333-1336.

5. Tabarra KF. Prevention of ligneous conjunctivitis by topical and subconjunctival fresh frozen plasma. Am J Ophthalmol. 2004;138(2):299-300.