Further investigation of Antithrombin

Coagulation

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Description

AT functions as an important natural anticoagulant forming inactive complexes with thrombin, factor IXa and factor Xa.

Two major subtypes of AT are recognised; type I is a quantitative reduction of qualitatively normal AT, and type II is due to the production of qualitatively abnormal form of AT. A congenital deficiency is associated with a thrombotic tendency and is often an autosomal dominant trait.

The Berichrom chromogenic assay (thrombin-based) measures antithrombin as heparin co-factor, and detects most Reactive Site (RS) and Heparin Binding Site (HBS) defects as well as Pleiotropic Effects (PE) and type I deficiency. The Berichrom assay has been optimized for maximum sensitivity to type II defects by reducing incubation time with thrombin to 30s.

AT deficiency with level below around 50% of normal may occasionally reduce the ability of heparin to anticoagulate and AT assay may be suggested by a Clinical Haematologist to investigate suspected heparin-resistance. In these cases, AT assay by Innovance FXa-based assay can be valuable and we have identified a number of heparin resistant patients with homozygous AT Budapest 3.

Further tests including FXa-based AT assay, progressive AT assay (AT assay in absence of heparin) and heparin-binding studies may be appropriate if type II AT deficiency is identified and tests requested by a Consultant haematologist. Genetic sequencing of the antithrombin gene (SERPINC1) can be requested from the Sheffield Genetics Service at Sheffield Children’s Hospital.

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Sample Type

Plasma (Citrate Blue) x 3.

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Reference Range

Indicated on report.

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Turnaround Time

Within 9 weeks

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Testing Frequency

As required.

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External Notes

Pregnancy and combined oral contraceptive pill may slightly suppress AT level, whereas severe liver disease and treatment with L-asparaginase can result in significantly reduced AT levels. On-going thrombosis especially with heparin therapy can reduce AT level. This thrombin-based method is not affected by direct FXa inhibitors such as Rivaroxaban, but direct thrombin inhibitors (e.g. Argatroban and Dabigatran) will significantly affect the result and give a falsely high level. 

An unexpected low level will trigger assay of AT antigen and further tests may be performed if requested by a Consultant Haematologist. Further investigation include Two-dimensional gel electrophoresis (+/- heparin), Xa-based AT assay, Progressive AT assay).

A prothrombin time is performed on all AT requests.

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References

Guidelines on the laboratory aspects of assays used in haemostasis and thrombosis Mackie I, P. Cooper, A. Lawrie, S. Kitchen, E. Gray, M. Laffan International journal of laboratory haematology. Volume 35, Issue 1, pages 1-13, February 2013
P. C. Cooper et al, The phenotypic and genetic assessment of antithrombin deficiency. International Journal of Laboratory Hematology. Volume 33, Issue 3, pages 227-237, June 2011.

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See Also

Thrombophilia Screen
Antithrombin
Antithrombin Antigen

Please note: the above information is subject to change and we endeavour to keep this website up to date wherever necessary.