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The Role of Antithrombin in Blood Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 December 2024 | Viewed by 1564

Special Issue Editor


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Guest Editor
Division of Clinical Laboratory Science, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
Interests: thrombosis; haemostasis; bleeding disorders; molecular genetics; laboratory medicine

Special Issue Information

Dear Colleagues,

Antithrombin (AT) is a member of the serine protease inhibitor (serpin) superfamily and is the most significant inhibitor of blood coagulation proteases. AT has two isoforms that differ only in their extent of glycosylation, where the less glycosylated form has a higher affinity for heparin. AT–heparin and AT–serine protease interactions have been extensively studied via in silico experiments. AT is encoded by SERPINC1 and hereditary AT deficiency is the most severe thrombophilia, which demonstrates clinical and laboratory heterogeneity. Founder mutations, such as AT Budapest 3, have been described. There are still several open questions concerning the management of AT deficient patients, eg., the application of NOAC, the administration of AT concentrate, the management of patients in pregnancy, etc. Acquired AT deficiency is also a clinical issue. The small interfering RNA, which reduces AT synthesis in hepatocytes, is considered to be one of the most promising “rebalancing” agents in the therapy of haemophilia. Moreover, AT may also play a role in other diseases.

This Special Issue focuses on AT deficiency, including hereditary and acquired, and all aspects of the role of AT in various diseases. Papers related to biochemistry, molecular biology, laboratory and clinical aspects of AT are considered for this Special Issue.

Dr. Zsuzsanna Bereczky
Guest Editor

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Keywords

  • antithrombin
  • antithrombin deficiency
  • thrombosis
  • haemophilia
  • laboratory tests
  • molecular genetics
  • anticoagulant therapy
 

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Published Papers (1 paper)

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Research

19 pages, 2002 KiB  
Article
Clinical and Molecular Characterization of Nine Novel Antithrombin Mutations
by Judit Kállai, Réka Gindele, Krisztina Pénzes-Daku, Gábor Balogh, Réka Bogáti, Bálint Bécsi, Éva Katona, Zsolt Oláh, Péter Ilonczai, Zoltán Boda, Ágnes Róna-Tas, László Nemes, Imelda Marton and Zsuzsanna Bereczky
Int. J. Mol. Sci. 2024, 25(5), 2893; https://doi.org/10.3390/ijms25052893 - 1 Mar 2024
Viewed by 1213
Abstract
Antithrombin (AT) is the major plasma inhibitor of thrombin (FIIa) and activated factor X (FXa), and antithrombin deficiency (ATD) is one of the most severe thrombophilic disorders. In this study, we identified nine novel AT mutations and investigated their genotype–phenotype correlations. Clinical and [...] Read more.
Antithrombin (AT) is the major plasma inhibitor of thrombin (FIIa) and activated factor X (FXa), and antithrombin deficiency (ATD) is one of the most severe thrombophilic disorders. In this study, we identified nine novel AT mutations and investigated their genotype–phenotype correlations. Clinical and laboratory data from patients were collected, and the nine mutant AT proteins (p.Arg14Lys, p.Cys32Tyr, p.Arg78Gly, p.Met121Arg, p.Leu245Pro, p.Leu270Argfs*14, p.Asn450Ile, p.Gly456delins_Ala_Thr and p.Pro461Thr) were expressed in HEK293 cells; then, Western blotting, N-Glycosidase F digestion, and ELISA were used to detect wild-type and mutant AT. RT-qPCR was performed to determine the expression of AT mRNA from the transfected cells. Functional studies (AT activity in the presence and in the absence of heparin and heparin-binding studies with the surface plasmon resonance method) were carried out. Mutations were also investigated by in silico methods. Type I ATD caused by altered protein synthesis (p.Cys32Tyr, p.Leu270Argfs*14, p.Asn450Ile) or secretion disorder (p.Met121Arg, p.Leu245Pro, p.Gly456delins_Ala_Thr) was proved in six mutants, while type II heparin-binding-site ATD (p.Arg78Gly) and pleiotropic-effect ATD (p.Pro461Thr) were suggested in two mutants. Finally, the pathogenic role of p.Arg14Lys was equivocal. We provided evidence to understand the pathogenic nature of novel SERPINC1 mutations through in vitro expression studies. Full article
(This article belongs to the Special Issue The Role of Antithrombin in Blood Disorders)
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