PB0555 - Hypoplasminogenemia: an International retroSpecTive and prOspective cohoRt studY (HISTORY): the international registry of patients with plasminogen deficiency

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Marzia menegatti, PhD

Biologist
Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy
MILAN, Lombardia, Italy

Co-Author(s)

JB

Joel Bowen

Project Manager
Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, United States
Indianapolis, Indiana, United States
MB

Marco Boscarino

Statistician
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy
Milan, Lombardia, Italy
CN

Charles Nakar

Physician
Indiana Hemophilia and Thrombosis Center
Indianapolis, Indiana, United States
RP

Roberta Palla

Biologist
Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy
MILAN, Lombardia, Italy
SS

Simona Maria Siboni

Hematologist
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center
Milan, Lombardia, Italy
Marcela Torres, MD

Hematologist
Cook Children's Medical Center
Fort Worth, Texas, United States
MB

Muhammed Batur

Clinician
Van Yuzuncu Yil University, Ophthalmology Department, Van, Turkey
Van, Van, Turkey
Rungrote Natesirinilkul, MD

Associate Professor
Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Chiang Mai, Chiang Mai, Thailand
CR

Chris Roberson

Director of Medical Programs
Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, United States
Indianapolis, Indiana, United States
HM

Heather McDaniel

Clinical Assistant Professor of Pediatrics
Vanderbilt University Medical Center, Division of Pediatric Hematology/Oncology, Nashville, TN, United States
Nashville, Tennessee, United States
SA

Serdar Al

Clinician
Dokuz Eylül University Research Clinical Immunology, Izmir, Turkey
Izmir, Izmir, Turkey
NR

Nidra Rodriguez

Pediatric Hematology Associate Professor
The 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
TC

Tiraje Celkan

Professor
Cerrahpaşa Faculty of Medicine, İstanbul University, Istanbul, Turkey
Istanbul, Istanbul, Turkey
JC

Jose Ceresetto

Clinician
Servicio de Hematología y Hemoterapia. Hospital Británico de Buenos Aires
CABA, Ciudad Autonoma de Buenos Aires, Argentina
NT

Neelam Thukral

Research Coordinator
Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, United States
Indianapolis, Indiana, United States
BH

Brandon M Hardesty

Clinician
Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, United States
Indianapolis, Indiana, United States
Flora Peyvandi, MD, PhD

Professor of Internal Medicine; Director of the Angelo Bianchi Bonomi Hemophilia & Thrombosis Center
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
Milan, Lombardia, Italy
AS

Amy Shapiro

Medical Director
Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA
Indianapolis, Indiana, United States

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.