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Hypoplasminogenemia: an International retroSpecTive and prOspective cohoRt studY (HISTORY): the international registry of patients with plasminogen deficiency

1Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy, Milan, Lombardia, Italy, 2Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, United States, Indianapolis, Indiana, United States, 3Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy, Milan, Lombardia, Italy, 4Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy, Milan, Lombardia, Italy, 5Cook Children’s Medical Center, Fort Worth, Texas, United States, 6Van Yuzuncu Yil University, Ophthalmology Department, Van, Turkey, Van, Van, Turkey, 7Faculty of Medicine Chiang Mai University, Chiang Mai, Thailand, Chiang Mai, Chiang Mai, Thailand, 8Vanderbilt University Medical Center, Division of Pediatric Hematology/Oncology, Nashville, TN, United States, Nashville, Tennessee, United States, 9Dokuz Eylül University Research Clinical Immunology, Izmir, Turkey, Izmir, Izmir, Turkey, 10The University of Texas Health Science Center at Houston, McGovern Medical School, Gulf States Hemophilia and Thrombophilia Center, Houston, TX, United States, Houston, Texas, United States, 11İstinye University, Istanbul, Turkey, Istanbul, Istanbul, Turkey, 12Servicio de Hematología y Hemoterapia. Hospital Británico de Buenos Aires, CABA, Ciudad Autonoma de Buenos Aires, Argentina, 13Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Department of Pathophysiology and Transplantation, and Fondazione Luigi Villa, Milan, Italy., Milan, Lombardia, Italy, 14Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana, United States

Abstract Number: PB0555

Meeting: ISTH 2022 Congress

Theme: Coagulation and Natural Anticoagulants » Coagulation Factors and Inhibitors

Background: Plasminogen (PLG) deficiency (PLGD), a rare inherited chronic disorder, affects ~1.6 per million population. Uncontrolled growth of fibrin‐rich pseudomembranes on mucous membranes of eyes, oral cavity, middle ears, respiratory, GU, GI, renal tracts, CNS, and skin is associated with morbidity and mortality. Ligneous conjunctivitis is the most common manifestation (~80%) and may lead to sight loss. Data regarding management of patients with PLG deficiency is scarce and based on case reports/series and small clinical trials. In 2021, the USFDA approved the first IV PLG concentrate; another specific therapy, PLG ophthalmologic concentrate, is not commercially available.

Aims: HISTORY is the first comprehensive retrospective/prospective international registry created to investigate PLGD natural history, and ultimately develop severity categories and treatment guidelines.

Methods: Up to 100 probands with their 1st degree non-affected family members will be enrolled in the 4 ‐year study. Clinical, genetic, and laboratory data are collected at baseline, and PLGD-related symptoms at study visits; unscheduled visits are included (new lesions, pregnancy). Specimens are collected for PLG activity (PLG:C), antigen (PLG:Ag), and molecular characterization.

Results: To date, 11 centers (6 countries) are actively enrolling with 115 subjects entered. Analysis was performed on 27 subjects (21 probands, 6 siblings) with complete data available; Table 1 includes demographic data and most frequently affected areas. Mean PLG:C and PLG:Ag were 15.3% (nr 80 – 132%) and 15.8 ug/ml (nr 70 – 215), respectively. Eyes and ear lesions were reported early in life, 1 and 3.5 years (median), respectively (Figure).

Conclusion(s): HISTORY is the first comprehensive retrospective/prospective international registry to document and evaluate PLGD current knowledge gaps. This first analysis demonstrates a significant decrease in PLG:C and PLG:Ag levels in affected patients, and that severe symptoms including eye and ear lesions occur early in life. Interestingly, the study has not yet recorded a subject of African descent.

Table

Demographic data and most frequently affected areas

Figure

Age at first symptom

To cite this abstract in AMA style:

Menegatti M, Bowen J, Boscarino M, Nakar C, Palla R, Siboni S, Torres M, Batur M, Natesirinilkul R, Roberson C, McDaniel H, Al S, Rodriguez N, Celkan T, Ceresetto J, Thukral N, Hardesty B, Peyvandi F, Shapiro A. Hypoplasminogenemia: an International retroSpecTive and prOspective cohoRt studY (HISTORY): the international registry of patients with plasminogen deficiency [abstract]. https://abstracts.isth.org/abstract/hypoplasminogenemia-an-international-retrospective-and-prospective-cohort-study-history-the-international-registry-of-patients-with-plasminogen-deficiency/. Accessed October 1, 2023.

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