Abstract Number: PB0742
Meeting: ISTH 2020 Congress
Theme: Fibrinolysis and Proteolysis » Fibrinolytic Factors and Inhibitors
Background: Plasminogen deficiency (PLGD), an ultra-rare, life-long, multi-system disorder affecting ~1.6 per million population, is characterized by uncontrolled growth of fibrin-rich pseudomembranes on mucous membranes. The most common manifestation is ligneous conjunctivitis (81% of patients) which can result in vision impairment/loss; other affected systems may include the oral cavity, respiratory tract, ears, female genitourinary tract, kidneys and CNS. Persons with PLGD (PwPLGD) have delayed/misdiagnosis and can suffer significant morbidity, reduction in quality of life, and mortality. No specific commercial therapies are available, current non-specific treatments are inadequate, and surgery results in pseudomembrane regrowth.
Aims: HISTORY (Hypoplasminogenemia: an International retroSpecTive and prOspective cohoRt studY) collects data from an international group of PwPLGD and their first-degree family members; its goal is to comprehensively investigate PLGD natural history and ultimately develop severity categories and treatment guidelines.
Methods: Up to 100 probands and 500 total subjects will be enrolled in the 4-year observational study (Figure 1) with IRB approval and informed consent. Clinical, genetic, and laboratory data are collected at baseline with additional data obtained at scheduled/unscheduled visits; specimens are collected to support planned and future research. Markers that assist in disease course prediction, triggers of disease manifestations and utility of diagnostic assays will be evaluated. Therapeutic interventions will be recorded along with efficacy and safety observations. HISTORY (NCT03797495) expands upon the database framework of the Prospective Rare Bleeding Disorders Database (PRO-RBDD).
[Figure 1: Outline of the 4-year clinical study. Subjects will spend a maximum of 3 years on-study.]
Results: To date, 26 centers in 12 countries have agreed to participate; 51 subjects are currently enrolled (Table 1). Initial results have identified asymptomatic siblings with PLGD; this affords a unique opportunity to investigate triggers of initial symptom development.
| Demographics | Subjects with PLGD | Unaffected family members | |
| Gender | Male | 9 | 11 |
| Female | 15 | 16 | |
| Age | <18 years | 14 | 8 |
| ≥18 years | 10 | 19 | |
| Endogenous PLG activity | Median (%) | 18.5 | n/a |
| Range (%) | 1 – 42* | n/a | |
| Endogenous PLG antigen | Median (mg/dL) | 3.4 | n/a |
| Range (mg/dL) | 1 – 12 | n/a | |
[Table 1: Demographics of the initial 51 subjects; n/a, not applicable; *The subject with 42% PLG received antibiotics prior to diagnostic sample]
Conclusions: HISTORY is the first comprehensive retrospective/prospective international registry to investigate the current knowledge gaps in PLGD. Due to the rarity of PLGD, all interested parties are strongly encouraged to participate. Additional information is available at www.plgdeficiency.com.
To cite this abstract in AMA style:
Shapiro A, Menegatti M, Palla R, Boscarino M, Siboni S, Torres M, Batur M, Natesirinilkul R, Roberson C, Lanzi P, Bowen J, Thukral N, Nakar C, Peyvandi F. HISTORY, an International Retrospective and Prospective Registry of Patients with Plasminogen Deficiency [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/history-an-international-retrospective-and-prospective-registry-of-patients-with-plasminogen-deficiency/. Accessed October 2, 2023.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/history-an-international-retrospective-and-prospective-registry-of-patients-with-plasminogen-deficiency/