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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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Antithrombin deficiency and its laboratory diagnosis

1, 2 / Zsuzsanna Bereczky1, 2 / Bettina Kovács3 / István Komáromi2

1Clinical Research Center, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary

2Thrombosis, Haemostasis and Vascular Biology Research Group of the Hungarian Academy of Sciences, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary

3Borsod Abaúj Zemplén County and Teaching Hospital, Miskolc, Hungary

Corresponding author: László Muszbek, MD, PhD, Clinical Research Center, University of Debrecen, Medical and Health Science Center, 98, Nagyerdei krt., Debrecen, 4032, Hungary Phone: +36 52 431 956, Fax: +36 52 340 011

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 48, Pages S67–S78, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2010.368, November 2010

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Antithrombin (AT) belongs to the serpin family and is a key regulator of the coagulation system. AT inhibits active clotting factors, particularly thrombin and factor Xa; its absence is incompatible with life. This review gives an overview of the protein and gene structure of AT, and attempts to explain how glucosaminoglycans, such as heparin and heparan sulfate accelerate the inhibitory reaction that is accompanied by drastic conformational change. Hypotheses on the regulation of blood coagulation by AT in physiological conditions are discussed. Epidemiology of inherited thrombophilia caused by AT deficiency and its molecular genetic background with genotype-phenotype correlations are summarized. The importance of the classification of AT deficiencies and the phenotypic differences of various subtypes are emphasized. The causes of acquired AT deficiency are also included in the review. Particular attention is devoted to the laboratory diagnosis of AT deficiency. The assay principles of functional first line laboratory tests and tests required for classification are discussed critically, and test results expected in various AT deficiency subtypes are summarized. The reader is provided with a clinically oriented algorithm for the correct diagnosis and classification of AT deficiency, which could be useful in the practice of routine diagnosis of thrombophilia.

Clin Chem Lab Med 2010;48:S67–78.

Keywords: amydolytic assay; antithrombin, antithrombin deficiency; thrombophilia

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