Page 40 - Haematologica March 2020

Ferrata Storti Foundation
Haematologica 2020 Volume 105(3):554-561
An international registry of patients with plasminogen deficiency (HISTORY)
Amy D. Shapiro,1 Marzia Menegatti,2 Roberta Palla,3 Marco Boscarino,2 Christopher Roberson,1 Paolo Lanzi,4 Joel Bowen,5 Charles Nakar,1 Isaac A. Janson1 and Flora Peyvandi2,3
1Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA; 2Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi Villa, Milan, Italy; 3Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy; 4Misto s.r.l., Milan, Italy and 5Rho, Inc., Durham, NC, USA
ABSTRACT
Plasminogen deficiency is an ultra-rare multisystem disorder charac- terized by the development of fibrin-rich pseudomembranes on mucous membranes. Ligneous conjunctivitis, which can result in vision impairment or loss, is the most frequent symptom reported. Affected systems may also include the respiratory tract, oropharynx, female reproductive tract, gingiva, middle ear, renal collecting system, skin and central nervous system. Untreated, plasminogen deficiency may result in significant reduction in quality of life and morbidity with poten- tial life-threatening complications. Non-specific therapies are inadequate and plasminogen concentrates are not commercially available. The cur- rent understanding of plasminogen deficiency and management of disease symptoms and its progression are based on case reports/series and two small clinical trials. To date there has never been a comprehensive, inter- national study to examine the natural history or optimal therapeutic inter- vention; knowledge gaps include identification of contributing factors and triggers of disease manifestations, inability to predict disease course, and insufficient real-world data for use of therapeutics. We have created an international, observational study (HISTORY) in a large cohort of persons with plasminogen deficiency and first-degree family members to address these gaps and to advance knowledge and care. HISTORY will build upon the established relationship between the Indiana Hemophilia and Thrombosis Center and the Fondazione Angelo Bianchi Bonomi, IRCCS Ca’ Granda Ospedale Maggiore Policlinico - University of Milan and will utilize a modified version of the Prospective Rare Bleeding Disorders Database (PRO-RBDD). A biorepository containing samples from sub- jects with plasminogen deficiency will be established. This article describes the rationale behind the study and efforts towards its goals.
Introduction
Diseases are defined as rare if they affect fewer than 200,000 people in the United States of America (USA) or fewer than 1 in 2,000 in the European Union; there are estimated to be approximately 6,500 clinically distinct rare diseases across all medical specialties.1 Given the large number of diseases meeting this broad classification, the term ‘ultra-rare disease’ has emerged to describe the rarest of these disorders; this phrase is not well defined, but in the United Kingdom (UK) it has come to mean fewer than 1,000 patients in that country (approximately 1 in 65,000). These diseases pose unique considerations for the researcher, clinician and patient; these range from an understanding of the natural history of the dis- ease and accurate diagnosis, to safe and effective treatment options and availabil- ity of knowledgeable specialists.
Randomized and large prospective clinical trials are often not feasible for ultra- rare diseases as the limited number of eligible patients and phenotypic hetero-
Correspondence:
AMY D. SHAPIRO
ashapiro@IHTC.org
Received: October 22, 2019. Accepted: January 20, 2020. Pre-published: January 30, 2020.
doi:10.3324/haematol.2019.241158
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/3/554
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