Coagulation
Coagulation laboratory tests
Antithrombin assay
Author: Jeremy C. Parsons, M.D.
Last author update: 1 June 2012
Last staff update: 11 September 2020
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: Antithrombin assay [title]
Cite this page: Parsons JC. Antithrombin assay. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/coagulationantithrombin.html. Accessed June 3rd, 2023.
Definition / general
- 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:
- 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 patients antithrombin
- 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:
- 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)
- 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
Etiology
- 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
Laboratory
- Specimen / reference ranges:
- 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:
- 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)
Additional references
