Dr. Amy Shapiro, Medical Director and CEO, Innovative Hematology & Indiana Hemophilia & Thrombosis Center, provided a THSNA “rare disorders presentation, Diagnosing plasminogen deficiency–clinical and laboratory considerations. Abstract:
Type 1 plasminogen deficiency (PLGD) or hypoplasminogenemia is an ultrarare disorder caused by pathogenic variants in the PLG, resulting in decreased functional and antigenic plasminogen levels. PLGD results in the development of fibrin-rich lesions, which accumulate on mucosal surfaces that may impair organ function and ultimately cause significant morbidity and, in some cases, mortality. PLGD is a systemic disorder affecting a variety of physiological systems, including ophthalmologic, oropharynx, respiratory, auditory, CNS, gynecologic, renal/urinary, and GI tract. Plasminogen is produced primarily in the liver but also in lesser amounts in the cornea, kidneys, adrenal glands, brain, testes, intestines, genital tract, and vascular linings. PLGD is an autosomal recessive disorder resulting from homozygous or compound heterozygous alterations in PLG. The reported prevalence is 1.6 cases per million population with a female-to-male ratio ranging between 1.4-2.0 to 1, likely due to the presence of symptoms in the female genital tract. Symptoms may wax and wane over time or be persistent; affected individuals may present across the entire age range.
Fibrin promotes activation of fibrinolysis through facilitation of both plasminogen and plasminogen activators binding to its surface, with subsequent cleavage of plasminogen into plasmin. Plasminogen’s other functions include complement inhibition, extracellular matrix degradation, cell migration, and inflammation resolution. Although plasminogen physiologically functions as a key enzyme in fibrinolysis, the clinical manifestations of PLGD do not include spontaneous thrombotic events.
The diagnostic journey for patients affected with PLGD is often quite delayed due to its rarity and multisystem manifestations, causing a wide variability in the initial point of medical contact including primary care, ophthalmology, dental, ENT, GYN, pulmonology, etc.
The diagnosis of PLGD is made through evaluation of plasminogen activity and antigen levels; diagnosis may also be triggered through pathological/histological analysis of removed pseudomembranes. If PLGD is suspected based upon histology, the levels of plasminogen activity and antigen should be ascertained. Siblings should be tested preemptively, even if asymptomatic, to determine their status.
Historically, no therapeutic intervention was available that consistently prevented or resolved PLGD-associated lesions. In 2021, the first specific replacement therapy for PLGD was approved by the FDA, a Glu-plasminogen concentrate manufactured from human plasma. This product has demonstrated safety and efficacy in the treatment of the myriad manifestations of PLGD with stable pharmacokinetics over time. There remain significant knowledge gaps in the treatment of PLGD, including clinicians’ lack of familiarity with the disease, substantial diagnostic delays, under-recognition of the systemic manifestations often attributed to more common etiologies, lack of defined and validated severity categories, and an inability to consistently predict who requires continuous versus intermittent therapy, and contributing factors that impact individual disease course.
This presentation reviews plasminogen structure and function, PLGD clinical manifestations, its current treatment, and knowledge gaps that remain to be addressed.
Here is a current publication available from your medical library: Shoshany TN, Thomson A, Shapiro A, Sura A, Nakar C, Perry HD. Advancing understanding of ligneous conjunctivitis: bridging pathogenesis, diagnosis, and therapy. Cornea. 2025;44:1451–7. doi: 10.1097/ICO.0000000000003987. PMID: 40929001.
Abstract
Purpose: This review and case report address ligneous conjunctivitis (LC), a rare ocular condition caused by plasminogen deficiency type 1 (PLGD-1), which manifests as wood-like fibrin-rich membranes on the palpebral conjunctiva. The goal is to provide ophthalmologists-often the first physicians to encounter the condition-with a robust understanding of its systemic manifestations and to highlight current therapeutic strategies, with particular emphasis on the administration of intravenous plasminogen concentrate.
Methods: We present a clinical LC case alongside a narrative review of published cases, etiology, and treatment approaches.
Results: LC initially manifests as erythematous lesions on the palpebral conjunctiva, eventually developing into fibrinous, wood-like membranes. It is typically associated with PLGD-1, a genetic disorder of the plasminogen gene ( PLG ), which results in impaired fibrinolysis and the formation of fibrin deposits. LC often appears within the first year of life, but patients may experience a prolonged period before diagnosis. PLGD-1 is also associated with the development of mucosal lesions in many other organ systems. Contributing factors include chronic inflammation, allergens, infections, and trauma. There have been many proposed treatment approaches for LC, but the recent approval of intravenous plasma-derived human plasminogen concentrate replacement has been an important advance.
Conclusions: LC is an ocular disorder with potential vision- and life-threatening complications. The treatment of LC has historically been challenging; however, recognition of its association with PLGD-1 has led to more effective therapies, particularly intravenous plasminogen concentrate. Early diagnosis and coordinated care between ophthalmologists and other specialists, such as hematologists, are crucial to prevent complications, including vision loss.
No comments here.