How we treat severe inherited antithrombin deficiency: lessons from cases homozygous for the Budapest 3 variant.

IF 5.5 2区医学 Q1 HEMATOLOGY

Journal of Thrombosis and Haemostasis Pub Date : 2025-02-09 DOI:10.1016/j.jtha.2025.01.015

Carlos Bravo-Pérez, Javier Corral, Christelle Orlando, Vera Ignjatovic, Péter Ilonczai, Zsuzsanna Bereczky

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引用次数: 0

Abstract

Background: Antithrombin deficiency represents one of the most severe inherited thrombophilias. Albeit a rare disorder, available knowledge suggests that antithrombin deficiency is underestimated due to the limitations of current diagnostic algorithms. The high clinical variability of this patient population may be another cause of underdiagnosis. Heterozygous type I (quantitative) variants are normally associated with a severe thrombophilic phenotype, while heterozygous type II (qualitative) variants are heterogeneous, including heparin-binding site defects, which are mild/moderate and the most prevalent. Antithrombin Budapest 3 (p.Leu131Phe) is the most frequent type II/heparin-binding site deficiency in Europe, particularly in the Roma population, with a remarkable existence of homozygous subjects.

Objectives: To determine the clinical features, diagnostic procedures, and management of patients with severe antithrombin deficiency, leveraging the study of cases homozygous for the antithrombin Budapest 3 variant.

Methods: Patients were selected from 699 subjects with antithrombin deficiency and recruited over 25 years from reference centers in Spain, Belgium, and Hungary.

Results: Guided by 2 illustrative cases with homozygous antithrombin Budapest 3, we report the spectrum and clinical management of patients with this disorder. These cases, with very low antithrombin activity (<20%) and juvenile and recurrent venous thromboembolism, recapitulate numerous issues that one might encounter when treating patients with antithrombin deficiency. In addition, special clinical scenarios for which no formal evidence-based guidelines exist might be found more frequently in these patients, including heparin resistance, vena cava anomalies, and obstetric complications.

Conclusion: Expert proposals on the optimal management of these controversial areas, as well as future perspectives, are also formulated.

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来源期刊

Journal of Thrombosis and Haemostasis 医学-外周血管病

CiteScore

24.30

自引率

3.80%

发文量

321

审稿时长

1 months

期刊介绍： The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.