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Antithrombin III activity

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CONVENTIONAL UNITS

(Functional Antithrombin Assay – Natural Anticoagulant)

Synonyms

  • Antithrombin III
  • AT III
  • Antithrombin activity
  • AT functional assay
  • SERPINC1 (gene name)
  • Heparin cofactor

Units of Measurement

  • % (percent activity)
  • U/mL
  • kU/L
  • Proportion (ratio or fraction of normal)

1 U/mL = 1 kU/L = 100% activity
 (Units are equivalent and reflect “functional activity relative to normal plasma.”)

Description

Antithrombin (AT) is a serine protease inhibitor (serpin) that inactivates key coagulation enzymes:

  • Thrombin (Factor IIa)
  • Factor Xa
  • Factor IXa
  • Factor XIa
  • Factor XIIa

AT is the most important natural anticoagulant in the body.
Heparin greatly accelerates AT activity → this is why heparin requires adequate AT levels to work.

The AT activity assay measures functional inhibition of thrombin or factor Xa, and is used to diagnose:

  • Inherited AT deficiency
  • Acquired AT deficiency
  • Heparin resistance
  • Unexplained thrombosis

Physiological Role

  • Major regulator of coagulation
  • Prevents excessive clot formation
  • Works synergistically with heparin and endothelial heparan sulfate
  • Inhibits coagulation proteases by forming irreversible complexes

Clinical Significance

Low Antithrombin Activity (Most Important)

1. Inherited Antithrombin Deficiency

  • Autosomal dominant (SERPINC1 gene)
  • Two types:
    • Type I: quantitative deficiency → ↓ AT antigen & ↓ activity
    • Type II: qualitative defect → normal antigen, ↓ activity
  • Strong risk of venous thromboembolism (VTE)
  • Often presents before age 40

2. Acquired AT Deficiency

Common causes:

  • Heparin therapy (consumes AT)
  • Liver disease (reduced synthesis)
  • Nephrotic syndrome (urinary loss)
  • DIC
  • Sepsis
  • Major surgery or trauma
  • Pregnancy (mild physiologic decrease)

Acquired deficiency is far more common than inherited.

3. Heparin Resistance

Low AT causes poor response to heparin, often requiring:

  • Higher doses
  • Switching to LMWH or direct anti-Xa agents
  • AT concentrate (rare situations)

High Antithrombin Activity

Not clinically significant.
Mildly elevated levels occur with:

  • Estrogen therapy
  • Some liver disorders

Reference Intervals

(Tietz 8E + ISTH + Mayo + ARUP)

Antithrombin Activity (Functional Assay)

  • 80–120% activity
     = 0.8–1.2 U/mL
     = 0.8–1.2 kU/L

Mild Deficiency

  • 60–80%

Moderate–Severe Deficiency

  • < 60%

Critical Values

  • < 50% → high VTE risk
  • < 30% → severe inherited deficiency; high thrombosis risk in young adults

Newborns

  • Lower (30–70%); reach adult levels by 6 months

Pregnancy

  • Physiologic decrease to ~70–90%

Examples

  • 80% = 0.8 U/mL = 0.8 kU/L = 0.80 proportion
  • 50% = 0.5 U/mL = 0.5 kU/L = 0.50 proportion

No molecular-weight based conversion applies (functional assay, not mass assay).

Diagnostic Uses

1. Workup of Unprovoked Venous Thrombosis

Especially in:

  • Young patients
  • Recurrent VTE
  • Family history of thrombosis

2. Heparin Resistance Investigation

Low AT explains insufficient aPTT/anti-Xa response to heparin.

3. DIC and Sepsis Monitoring

AT is consumed, correlating with disease severity.

4. Liver Disease Evaluation

AT tracks synthetic liver function.

5. Neonatal Evaluation

Low neonatal AT may cause thrombosis in rare congenital cases.

Analytical Notes

  • Functional assays use chromogenic anti-thrombin activity tests.
  • Heparin interferes: high heparin → falsely low AT (use heparin-neutralizing reagents).
  • Blood should be collected in citrate tubes.
  • Test not reliable during acute thrombosis or on anticoagulants.
  • Repeat testing recommended once acute phase/treatment resolves.

Clinical Pearls

  • Test AT before starting anticoagulation, when possible.
  • Heparin resistance is often due to low AT; LMWH or DOACs bypass this issue.
  • Inherited AT deficiency has highest thrombosis risk among all thrombophilias.
  • Pregnancy lowers AT → important in recurrent fetal loss/VTE evaluation.
  • Antithrombin concentrates may be used in rare severe deficiency during surgery/pregnancy.

Interesting Fact

Antithrombin was once called “Antithrombin III”, but the numbering is now obsolete. Modern guidelines use the term “Antithrombin” only.

References

  1. Tietz Clinical Chemistry and Molecular Diagnostics, 8th Edition - Coagulation Factors & Antithrombin.
  2. ISTH Guidelines - Thrombophilia & Natural Anticoagulant Testing.
  3. ACCP Antithrombin & Anticoagulation Recommendations.
  4. Mayo Clinic Laboratories - Antithrombin Activity Test.
  5. ARUP Consult - Thrombophilia Evaluation.
  6. IFCC Coagulation Standardization Guidelines.
  7. MedlinePlus / NIH - Antithrombin Test Overview.

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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