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An international registry of patients with plasminogen deficiency (HISTORY).

ABSTRACT: Plasminogen deficiency is an ultra-rare multisystem disorder characterized 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 potential life-threatening complications. Non-specific therapies are inadequate and plasminogen concentrates are not commercially available. The current 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, international study to examine the natural history or optimal therapeutic intervention; 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 subjects with plasminogen deficiency will be established. This article describes the rationale behind the study and efforts towards its goals.

SUBMITTER: Shapiro AD

PROVIDER: S-EPMC7049368 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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An international registry of patients with plasminogen deficiency (HISTORY).

Shapiro Amy D AD Menegatti Marzia M Palla Roberta R Boscarino Marco M Roberson Christopher C Lanzi Paolo P Bowen Joel J Nakar Charles C Janson Isaac A IA Peyvandi Flora F

Haematologica 20200130 3

Plasminogen deficiency is an ultra-rare multisystem disorder characterized 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 reductio ...[more]

PMID: 32001536

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Project description:BackgroundPublished data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear.ObjectivesThe purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre-COVID-19 cohorts.MethodsFrom March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re-myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre-COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019).ResultsIn 144 ST-segment elevation myocardial infarction (STEMI) and 121 non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p < 0.001; COVID NSTE-ACS vs. MINAP: 417.0 min vs. 295.0 min; p = 0.012). Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs. 5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs. 1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 [95% confidence interval: 2.04 to 5.42]). Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001).ConclusionsIn this multicenter international registry, COVID-19-positive ACS patients presented later and had increased in-hospital mortality compared with a pre-COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients.

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Dataset Information

An international registry of patients with plasminogen deficiency (HISTORY).

Publications

An international registry of patients with plasminogen deficiency (HISTORY).

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