Thank you for attending THSNA 2026. The virtual meeting is now closed.
| Diagnosing plasminogen deficiency - clinical and laboratory considerations Amy Shapiro. |
Abstract
Diagnosing plasminogen deficiency – clinical and laboratory considerations
Amy D. Shapiro, MD
Medical Director, CEO
Innovative Hematology & Indiana Hemophilia & Thrombosis Center
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 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 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 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 is 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 clinician lack of disease familiarity with substantial diagnostic delays, under-recognition of the systemic manifestations often attributed to more common etiologies, lack of defined and validated severity categories with 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.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.