An Antithrombin III Assay Based on Factor Xa Inhibition Provides a More Reliable Test to Identify Congenital Antithrombin III Deficiency Than an Assay Based on Thrombin Inhibition

Demers, Christine; Henderson, Penny; Blajchman, Morris A.; Wells, Michael J.; Mitchell, Lesley; Johnston, Marilyn; Ofosu, Frederick A.; Fernandez-Rachubinski, F; Andrew, Maureen; Hirsh, Jack

doi:10.1055/s-0038-1651586

Cited by 53 publications

(40 citation statements)

References 16 publications

(15 reference statements)

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“…This method is routinely used in clinical practice, because it is the most reliable test to identify congenital antithrombin deficiency. 17 The prevalence of the classic prothrombotic polymorphisms was similar to that described in other series. Thus, the FV Leiden was present in 145 patients (3 in homozygous state) (14.2%), and the prothrombin 20210A allele was identified in 101 patients (7 in homozygous state) (9.9%) ( Table 1).…”

Section: Case-control Studysupporting

confidence: 85%

“…Moreover, 62 carriers, including 4 homozygous subjects (from the studies of Tait et al, 13 Perry et al, 21 and this study) have normal plasma levels of antithrombin antigen (99.5% Ϯ 13.1%). Because these are the methods commonly used to identify antithrombin deficiency, 17,22 we can understand why this mutation has not been identified in other populations, and, probably, its prevalence had been underestimated. Moreover, this variant only slightly impaired the anti-IIa activity (74.3% Ϯ 8.5%) of 60 carriers (from the studies of Tait et al, 13 Perry et al, 21 and this study).…”

Section: Discussionmentioning

confidence: 99%

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Antithrombin Cambridge II (A384S): an underestimated genetic risk factor for venous thrombosis

Corral

Hernández-Espinosa

Soria

et al. 2007

Blood

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The antithrombin A384S mutation has a relatively high frequency in the British population but has not been identified in other populations. This variant has been associated with cases of thrombotic disease, but its clinical relevance in venous thrombosis remained unclear. We have conducted a secondary analysis of the prevalence of the mutation in a large case-control study, including 1018 consecutive Spanish patients with venous thromboembolism. In addition, we evaluated its functional consequences in 20 carriers (4 homozygous). This mutation, even in the homozygous state, did not affect anti-Xa activity or antigen levels, and it only slightly impaired anti-IIa activity. Thus, routine clinical methods cannot detect this anomaly, and, accordingly, this alteration could have been underestimated. We identified this mutation in 0.2% of Spanish controls. Among patients, this variant represented the first cause of antithrombin anomalies. Indeed, 1.7% patients carried the A384S mutation, but 0.6% had any other antithrombin deficiency. The mutated allele was associated with an increased risk of venous thrombosis with an adjusted OR of 9.75 (95% CI, 2.2-42.5). This is the first study supporting that antithrombin A384S mutation is a prevalent genetic risk factor for venous thrombosis and is the most frequent cause of antithrombin deficiency in white populations. (Blood. 2007;109: [4258][4259][4260][4261][4262][4263]

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Section: Case-control Studysupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Antithrombin Cambridge II (A384S): an underestimated genetic risk factor for venous thrombosis

Corral

Hernández-Espinosa

Soria

et al. 2007

Blood

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“…Human thrombin also reacted with heparin cofactor II and made the assay relatively insensitive for the detection of AT deficiency (89,90). In most commercial kits, human thrombin has been replaced by bovine thrombin which shows minimal reaction with heparin cofactor II.…”

Section: Laboratory Diagnosis Of Antithrombin Deficiencymentioning

confidence: 99%

Antithrombin deficiency and its laboratory diagnosis

Muszbek¹,

Bereczky²,

Kovács³

et al. 2010

Clinical Chemistry and Laboratory Medicine

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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.

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“…Total protein S antigen, 1 free protein S antigen 15 and functional protein S activity 16 were measured according to the manufacturer's instructions (Roche diagnostics, Tokyo). Antithrombin III activity, 18 functional protein C activity 19 and protein C antigen were measured according to the manufacturer's instructions (Daiiti-kagakuyakuhin, Sismex, and Iatron Laboratories, Inc, respectively). Although the total amount of protein S antigen was 65% (at around the lower limit of normal), the level of free protein S antigen was significantly low (31%).…”

mentioning

confidence: 99%

Hereditary Protein S Deficiency With a History of Recurrent Myocardial Infarction. A Case Report.

Ogasawara

Kijima

Ike

et al. 2003

Circ J

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An Antithrombin III Assay Based on Factor Xa Inhibition Provides a More Reliable Test to Identify Congenital Antithrombin III Deficiency Than an Assay Based on Thrombin Inhibition

Cited by 53 publications

References 16 publications

Antithrombin Cambridge II (A384S): an underestimated genetic risk factor for venous thrombosis

Antithrombin Cambridge II (A384S): an underestimated genetic risk factor for venous thrombosis

Antithrombin deficiency and its laboratory diagnosis

Hereditary Protein S Deficiency With a History of Recurrent Myocardial Infarction. A Case Report.

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