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REVIEW ARTICLE

Neurological manifestations, thrombosis, and cancer in Arg393His antithrombin Hanoi

Khue Vu Nguyen1,2,3,4*
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1 School of Medical Imaging, Jiangsu Medical College, Yancheng, Jiangsu, China
2 Medical Imaging Institute of Jiangsu Medical College, Yancheng, Jiangsu, China
3 Center for Molecular Biophysics, CNRS Orleans, Orleans, Loiret, France
4 School of Medicine, Departments of Medicine and Pediatrics, Biochemical Genetics and Metabolism, The Mitochondrial and Metabolic Disease Center, University of California, San Diego, California, United States of America
Brain & Heart, 025450071 https://doi.org/10.36922/BH025450071
Received: 4 November 2025 | Revised: 14 January 2026 | Accepted: 11 February 2026 | Published online: 8 April 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Antithrombin (AT) deficiency is associated with the highest risk of thrombotic events in both veins and arteries, which underlie strokes, heart attacks (myocardial infarction), peripheral artery disease, and even certain cancers. This review provides (i) a family case describing a “two-way association” between cancer—including kidney cancer, melanoma—and thrombosis such as stroke (encephalomalacia/gliosis) and deep venous thrombosis arising from a heterozygous Arg393His mutation in AT-Hanoi; (ii) a discussion concerning the multifaceted roles of AT beyond its anticoagulant function, including its involvement in host defense, inflammation, anti-angiogenesis and tumorigenesis, establishing AT as a pleiotropic protein; and (iii) perspectives exploring the potential implication of the β-amyloid precursor protein gene in the development of neurological features, thrombotic events and cancer, followed by a discussion on different types of immunotherapy used for the treatment of cancer, such as chimeric antigen receptor T-cell therapy and immune checkpoint inhibitor, as well as on the potential application of sonogenetics for non-invasive therapy of human diseases. This Arg393His point mutation in AT-Hanoi could be selected as a model of a rare hereditary blood-clotting disorder for the development of valuable drugs to modulate the coagulation cascade and thereby prevent the consequences of blood-clotting disorders that are partly responsible for neurological and cardiovascular diseases, as well as cancer.

Keywords
Arg393His antithrombin Hanoi
BRAF mutation
β-amyloid precursor protein
CAR T-cell therapy
Expression vectors via glycosylphosphatidylinositol
Immune checkpoint inhibitor
Melanoma
Sonogenetics
Funding
None.
Conflict of interest
The author declares no conflict of interest.
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