Antithrombin III (AT III) Test (26)
🩸 Antithrombin III (AT III) Test: Purpose, Method, Reference Range, and Clinical Significance
Antithrombin III (AT III) is one of the most important natural anticoagulant proteins in the human body. It plays a crucial role in preventing excessive blood clot formation by inhibiting several coagulation factors.
The Antithrombin III test measures the activity of this protein in plasma and is commonly used in the evaluation of thrombotic disorders and coagulation abnormalities.
1. What is Antithrombin III (AT III)?
Antithrombin III is a glycoprotein produced mainly by the liver that functions as a key inhibitor of the coagulation cascade.
Its primary role is to inactivate major clotting enzymes, including:
- Thrombin (Factor IIa)
- Factor Xa
- Factor IXa
- Factor XIa
- Factor XIIa
By neutralizing these enzymes, AT III helps maintain the balance between coagulation and anticoagulation.
Antithrombin III is also an essential cofactor for heparin, and more than half of the anticoagulant effect of heparin therapy depends on adequate AT III activity.
2. Purpose of the AT III Test
The Antithrombin III test is performed in several clinical situations.
1) Evaluation of Thrombotic Disorders
AT III deficiency increases the risk of abnormal blood clot formation.
The test is often ordered in patients with:
- Deep vein thrombosis (DVT)
- Pulmonary embolism (PE)
- Recurrent thrombosis
- Thrombosis at a young age
- Recurrent pregnancy loss
2) Monitoring Anticoagulant Therapy
AT III testing is helpful in evaluating heparin resistance, a condition in which patients require unusually high doses of heparin to achieve anticoagulation.
Low AT III levels may reduce the effectiveness of heparin therapy.
3) Assessment of Liver Function
Because AT III is synthesized in the liver, chronic liver disease may lead to reduced production and decreased plasma levels.
4) Evaluation of Disseminated Intravascular Coagulation (DIC)
In DIC, coagulation factors and inhibitors are consumed rapidly.
AT III levels often decrease as the disease progresses.
3. Test Method: Chromogenic Assay
The most widely used method for measuring AT III activity is the chromogenic assay.
Principle
- Excess Factor Xa or thrombin is added to the plasma sample.
- Antithrombin III in the sample inhibits part of the enzyme.
- The remaining enzyme reacts with a chromogenic substrate, producing a color change.
- The color intensity is measured spectrophotometrically.
Interpretation
- Darker color → More remaining enzyme → Lower AT III activity
- Lighter color → Greater inhibition → Higher AT III activity
4. Reference Range
Typical reference values are:
Antithrombin III Activity: 80–120%
However, the reference range may vary slightly between laboratories, typically ranging from 70–130%.
5. Clinical Significance
Decreased AT III Levels
Reduced AT III activity can lead to increased thrombotic risk.
1) Hereditary Antithrombin Deficiency
Inherited AT III deficiency is one of the most severe hereditary thrombophilias.
Two main types exist:
- Type I: Reduced production of AT III
- Type II: Normal quantity but defective function
Affected individuals often develop recurrent venous thrombosis at a young age.
2) Acquired Causes of AT III Reduction
AT III levels may also decrease in several acquired conditions:
- Disseminated intravascular coagulation (DIC)
- Liver cirrhosis or liver failure
- Nephrotic syndrome (protein loss in urine)
- Severe infection or sepsis
- Major surgery or trauma
- Obstetric complications
AT III levels may also decrease during heparin therapy due to consumption of the inhibitor.
Increased AT III Levels
Elevated AT III levels generally have limited clinical significance.
They may occur in:
- Anticoagulant therapy (e.g., warfarin)
- Recovery phase after acute inflammation
- Postpartum physiological changes
6. Important Considerations in Interpretation
1) Effect of Heparin Therapy
Heparin accelerates AT III activity and may lead to temporary depletion of AT III.
For accurate results, testing is recommended 12–24 hours after discontinuation of heparin.
2) Acute Illness
During acute conditions such as:
- DIC
- Sepsis
- Major surgery
AT III levels may drop significantly.
Repeat testing after recovery may be necessary.
3) Combined Testing with Other Anticoagulant Proteins
For a complete evaluation of thrombophilia, AT III testing is often performed together with:
- Protein C
- Protein S
This combined approach improves diagnostic accuracy.
4) Pregnancy and Oral Contraceptives
AT III levels may be slightly reduced during pregnancy or oral contraceptive use, which should be considered during interpretation.
7. Summary of AT III Results
| Result | Interpretation | Associated Conditions |
|---|---|---|
| ↓ AT III | Increased thrombotic risk | DIC, liver failure, nephrotic syndrome, hereditary deficiency |
| Normal | Normal anticoagulant activity | Physiological state |
| ↑ AT III | Usually limited clinical significance | Anticoagulant therapy, recovery phase |
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8. References
- Hoffman R. Hematology: Basic Principles and Practice. 7th ed.
- Rodak BF. Hematology: Clinical Principles and Applications.
- Dacie JV, Lewis SM. Practical Haematology.
- Furie B, Furie BC. Antithrombin deficiency and thrombosis. New England Journal of Medicine.
- Clinical and Laboratory Standards Institute (CLSI).