Laboratory Tests for Plasminogen (PLG)
When lesions are suspected to be ligneous (the woody-like buildup of fibrin in the membranes that are characteristic of congenital Plasminogen Deficiency (PLGD)), your doctor may order tests that evaluate the PLG antigen and activity level in the body. The testing analysis (assays) will help determine if PLG activity and levels are both diminished, which would indicate congenital PLGD.¹ In mild cases of PLGD, PLG levels may be close to normal; however, the activity is decreased.²
Your doctor may also send a surgically removed lesion (biopsy) to the lab to determine if the biopsy demonstrates a buildup of fibrin-rich deposits when viewed under a microscope.³
Genetic testing is used to confirm or rule out suspected PLGD. The condition is caused by mutations in a gene that provide instructions to the body for making the protein called plasminogen. Parents each carry one copy of the mutated gene, but typically do not show any signs and symptoms of the condition.¹
There are other advantages to genetic testing. It can help guide treatment decision and long-term management, and it may provide a reason for the family to seek genetic counselling. You can begin to understand the course of the condition and identify members of your family who may also be at risk by screening for mutations. Genetic testing also informs you about reproductive risks and prenatal options, so you can make informed decisions and preparations.1, 4
What to Expect
Advances in science and technology are bringing new hope every year to patients with many conditions. This is especially true in the treatment of congenital PLGD. However, there is also a degree of the unknown because this is such a rare disorder.1, 5
The probable course of congenital PLGD can vary, depending on a variety of factors. These include the extent, location, length, and site of the lesions. Many affected individuals live through adulthood and have average life expectancy. However, in the absence of effective therapy, their quality of life is diminished.¹
Surgical removal of the growths may provide temporary relief, but these lesions often reappear. Patients may be subjected to dozens of more surgical procedures. In fact, some patients with recurring ligneous conjunctivitis have required more than 20 operations.¹
These lesions are often quite painful and can compromise organ function, creating emergencies, such as a collapsed lung, kidney failure, or blindness. In some cases, complications can be fatal.¹
While there is no cure, the promise of PLG replacement therapy, currently in clinical trials, offers new hope and relief for many sufferers.5, 6, 7
PLGD Therapy and Clinical Trials
A variety of treatments such as cyclosporine A, heparin, anti-inflammatories, and steroids have been tried in the management of PLGD; however, these have offered very little benefit or clinical improvement. The administration of plasminogen appears to provide the most relief and greatest benefit.8, 9, 10, 11
Prometic Life Sciences is developing a new plasminogen replacement therapy for congenital PLGD. A Phase 1 study in patients with congenital PLGD demonstrated the successful replacement of blood levels of PLG and showed it was well tolerated following a single dose of PLG. A Phase 2/3 study in patients with congenital PLGB is ongoing to determine the safety, tolerability, and the pharmacokkinetics (how the drug is processed by the body) of multiple infusions of PLG. This study will also explore the clinical effect of this drug on ligneous lesions in plasminogen-deficient patients. Final results of this study will be avaiable in late 2017.
Given the rarity and seriousness of the condition, Prometic is working with the FDA to facilitate an expedited review and approval of PLG. This only happens in serious conditions, where there is a meaningful advantage over currently available therapies. Clinical trials are ongoing.
More information about these clinical trials is available at ClinicalTrials.gov.
1. Mehta R, Shapiro AD. Plasminogen activator inhibitor type I deficiency. Haemophilia. 2008;14(6);1255-1260.
2. Tefs, K, Gueorguieva M, Klammt J, et al. Molecular and clinical spectrum of type I plasminogen deficiency: a series of 50 patients. Blood. 200;108(9);30-21-3026.
3. Kraft J, Lieb W, Zeitler P, Schuster V. Ligneous conjunctivitis in a girl with severe type I plasminogen deficiency [PMID abstract 11045349]. See comment in PubMed Commons below Graefes Arch Clin Exp Ophthalmol. 2000;238(9):797-800.
4. National Center for Biotechnology Information, US National Library of Medicine, 2015. Genetic Testing Registry: Plasminogen deficiency type I. http://www.ncbl.nlm.nih.gov/gtr/tests/527642/overview. Accessed May 14, 2016.
5. Schneppenheim R, Moran J, Hassenpflug W, Schrum J, Schneppenheim S, Müller-Stöver S. Pending publication in peer-reviewed journal.
6. Schott D, Dempfle C-E, Beck P, et al. Therapy with a purified plasminogen concentrate in an infant with ligneous conjunctivitis and homozygous plasminogen deficiency. N Engl J Med. 1998;339(23):1679-1686.
7. Kraft J, Lieb W, Zeitler P, Schuster V. Ligneous conjunctivitis in a girl with severe type I plasminogen deficiency [PMID abstract 11045349]. See comment in PubMed commmons below Graefes Arch Clin Exp Ophthalmol. 2000;238:797–800.
8. Heldemann DG, Williams GA, Hartzer M, Ohanian A, Citron ME. Treatment of ligneous conjunctivitis with topical plasmin and topical plasminogen. Cornea.2003;22(8):760-762.
9. Watts P, Suresh P, Mezer E, et al. Effective treatment of ligneous conjunctivitis with topical plasminogen. AM J Ophtalmol. 2002;133(4):451-455.
10. 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.
11. Tabbara KF. Prevention of ligneous conjunctivitis by topical and subconjunctival fresh frozen plasma. Am J Ophtalmol. 2004;138(2):299-300.
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