Coagulation - Antithrombin assay

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Coagulation

Coagulation laboratory tests

Antithrombin assay

Reviewer: Jeremy Parsons, M.D. (see Reviewers page)
Revised: 19 June 2012, last major update June 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

General
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● Assays detect antigenic (type I, reduced normal protein, quantitative) or functional (type II, normal amount of defective protein, qualitative) deficiencies of antithrombin (formerly called antithrombin III)
● Perform functional assay first - if decreased, perform antigenic assay on fresh specimen
● Family studies may be helpful

Functional assays
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● Are chromogenic, use predominantly amidolytic methods (i.e. through cleavage of an amide bond), employing a synthetic peptide that mimics the natural target of the enzyme
● Patient plasma is incubated with excess thrombin and heparin
● Antithrombin neutralizes thrombin, and remaining thrombin is then quantitated with a chromogenic substance
● The amount detected is inversely proportional to the patient’s antithrombin

Functional assay limitations
● False levels may be produced if high levels of heparin cofactor II are present; this is eliminated by assays that use inhibition of factor Xa rather than thrombin
● Newer assays have protease inhibitors to minimize nonspecific substrate cleavage and bovine thrombin
● Hirudin or argatroban anticoagulation may interfere with thrombin based assays

Antigenic assays
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● Quantification is usually via radial immunodiffusion techniques, although they have coefficients of variation of 40-50%
● Amidolytic assays have CV of only 9-14%
● Also used are latex particles coated with antithrombin antibodies (e.g. LIA)
● Light absorbance is related to the amount of antithrombin in the specimen
● Also family studies (first degree relatives)

Antigenic assay limitations
● Does not detect functional deficiencies by itself
● If initial antithrombin result is low, should do confirmatory test on repeat specimen
● Must also exclude acquired causes

Specimen / reference ranges
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● Plasma in sodium citrate tube
● Levels are lower in newborns; rise to adult levels (112-140 mg/liter) by age 6-12 months
● Mildly decreased values (70-80%) are unlikely to be associated with thrombosis

Indications
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● Evaluation of individuals with thrombophilia (strong family history or young patient)
● Also analyze for factor V Leiden and prothrombin G20210A
● Preferable to not test during the acute phase of a thrombotic event (normal antithrombin value makes antithrombin deficiency unlikely, although cannot interpret mildly abnormal values)

Acquired causes
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Acquired causes of low antithrombin levels:
● Clot formation
● Surgical procedures
● Liver disease
● Nephrotic syndrome
● DIC
● Heparin (full dose therapy decreases levels by up to 30%)
● L-asparaginase therapy
● Possibly pregnancy or oral contraceptives

Acquired causes of high antithrombin levels:
● Warfarin therapy

Additional references
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● Arch Pathol Lab Med 2002;126:1326, Thromb Diath Haemorrh 1965;13:516

End of Coagulation > Coagulation laboratory tests > Antithrombin assay

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