Can the test be done while on heparin?

Heparin consumes antithrombin and lowers plasma levels, so testing during heparin therapy may yield falsely low results. Ideally draw before starting heparin or defer thrombophilia evaluation until anticoagulation is complete, unless investigating heparin resistance specifically.

Why is timing important for antithrombin testing?

Antithrombin falls during acute thrombosis, heparin use, and critical illness, so testing during these periods may not reflect baseline hereditary status. Thrombophilia screening is most accurate when the patient is well, off anticoagulation, and at least six weeks past an acute clot.

Is fasting required for the antithrombin test?

No. Antithrombin does not require fasting, though the blood must be collected into citrate tubes and processed promptly to preserve protein stability.

What is heparin resistance and how does antithrombin relate to it?

Heparin resistance occurs when therapeutic heparin doses fail to prolong aPTT adequately. Because heparin's anticoagulant effect depends on antithrombin, low antithrombin levels blunt the response; measuring antithrombin identifies this mechanism and may prompt antithrombin concentrate replacement.

Does pregnancy affect antithrombin levels?

Pregnancy and oestrogen lower antithrombin modestly, so borderline results during pregnancy may require repeat testing postpartum to distinguish true hereditary deficiency from a physiological or hormonal reduction.

How long do antithrombin results take?

Results are typically available within 2–4 business days from specimen receipt at Quest. Coagulation assays may require batch processing or reference-laboratory send-out.

Should family members be tested if hereditary deficiency is found?

Yes. Hereditary antithrombin deficiency is autosomal dominant with high penetrance, so first-degree relatives have a 50% chance of carrying the defect and should be offered cascade screening, particularly before high-risk situations such as surgery, pregnancy, or oestrogen therapy.

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Antithrombin III Antigen

Q: What does low antithrombin indicate?

Low antithrombin suggests hereditary deficiency (a thrombophilia with high VTE risk) or acquired deficiency from heparin therapy, acute thrombosis, DIC, liver disease, nephrotic syndrome, or L-asparaginase chemotherapy. A single low result requires confirmation when the patient is stable and off anticoagulation.

The Antithrombin III Antigen test measures circulating antithrombin, the principal serine protease inhibitor of thrombin and factors IXa, Xa, XIa, XIIa. Deficiency — hereditary or acquired — increases venous thromboembolism risk and causes heparin resistance; the test is ordered in thrombophilia evaluation, unexplained VTE, and to investigate inadequate heparin response.

Biomarkers

Blood (plasma)

Sample

2–4 business days

Turnaround

Fasting

What is the Antithrombin III Antigen test?

The Antithrombin III Antigen test quantifies the circulating concentration of antithrombin, the principal endogenous inhibitor of thrombin and other coagulation proteases. It is ordered to investigate unexplained or recurrent venous thromboembolism, especially in younger patients or those with a family history, and forms part of the comprehensive thrombophilia evaluation alongside protein C, protein S, factor V Leiden, and prothrombin gene mutation. Antithrombin deficiency increases thrombotic risk substantially — hereditary deficiency confers one of the highest relative risks among the inherited thrombophilias — yet the test is rarely ordered in isolation. Practitioners pair antigen measurement with functional activity assays to distinguish type I (low antigen, low activity) from type II (normal antigen, reduced activity) deficiency. The test is also used to investigate heparin resistance, where low antithrombin limits the drug's anticoagulant effect, and to assess acquired deficiency in critically ill patients, those with liver disease, or nephrotic syndrome.

What does the Antithrombin III Antigen test measure?

AT III(Antithrombin III Antigen)

Range: Approximately 80–130% activity or 20–30 mg/dL antigen, age- and assay-dependent.Optimal: Most practitioners target the laboratory reference range (80–130%); values below 70% are considered deficient and warrant further investigation, particularly when recurrent thrombosis or a family history is present.% / mg/dL

Antithrombin III is a serine protease inhibitor synthesised by the liver that irreversibly inactivates thrombin (factor IIa) and factors IXa, Xa, XIa, and XIIa. Its anticoagulant activity is accelerated a thousand-fold by heparin, which binds a specific pentasaccharide sequence and changes the inhibitor's conformation. Antithrombin thus serves as the primary physiological brake on coagulation, and heparin's therapeutic effect depends entirely on adequate circulating antithrombin. The antigen assay quantifies the protein itself, regardless of functional activity, making it useful when distinguishing type I (quantitative) from type II (qualitative, dysfunctional) deficiency.

Antithrombin III deficiency — whether hereditary or acquired — is one of the inherited thrombophilias and a well-established risk factor for venous thromboembolism. Hereditary deficiency is rare, autosomal dominant, and associated with recurrent deep-vein thrombosis and pulmonary embolism, often presenting at a young age. Acquired deficiency is more common and seen during heparin therapy (consumption), in liver disease (reduced synthesis), nephrotic syndrome (urinary loss), disseminated intravascular coagulation, and acute thrombosis. The antigen test is ordered as part of a thrombophilia screen and to investigate heparin resistance, where low antithrombin blunts anticoagulant response.

Why is the Antithrombin III Antigen test ordered?

Investigation of unprovoked or recurrent venous thromboembolism, particularly in patients under 50 years or with a positive family history
Thrombophilia screening before initiating oestrogen therapy or during pregnancy planning in patients with a personal or strong family history of clot
Evaluation of heparin resistance, where therapeutic heparin doses fail to prolong activated partial thromboplastin time appropriately
Work-up of neonatal purpura fulminans or severe thrombosis in infancy, where homozygous antithrombin deficiency is suspected
Assessment of acquired deficiency in critically ill patients with disseminated intravascular coagulation or sepsis
Monitoring in nephrotic syndrome or severe liver disease, where synthesis or urinary loss of antithrombin may complicate anticoagulation management
Pre-operative thrombosis risk stratification in patients with known hereditary thrombophilia undergoing major surgery

Sample collection and turnaround

Sample type

Blood (plasma)

Fasting required

Collection method

Venipuncture at patient service centre

Turnaround

2–4 business days

Collection notes

Phlebotomy at a Quest patient service centre into sodium citrate (blue-top) tubes. Ideally draw before starting heparin or at least four hours after subcutaneous dosing. Avoid collection during acute thrombosis or DIC; defer until the patient is stable and off acute anticoagulation. Fill the tube to the correct volume to maintain the 9:1 blood-to-citrate ratio, as underfilling invalidates coagulation results.

Specimen requirements

Minimum 2 mL citrated plasma. Separate plasma within one hour of collection and refrigerate or freeze promptly. Antithrombin is stable refrigerated for up to 48 hours or frozen at –20°C for longer storage. Label the specimen with the patient's anticoagulation status and time since last heparin dose.

What can affect Antithrombin III Antigen results?

reducesHeparin therapy (unfractionated or low-molecular-weight)

Heparin binds and consumes antithrombin during anticoagulation, lowering plasma levels; ideally draw before starting heparin or at least four hours after the last subcutaneous dose to minimise acute consumption.

reducesAcute thrombosis or disseminated intravascular coagulation

Consumption of antithrombin during active clot formation and DIC lowers antigen and activity transiently; defer thrombophilia testing until the acute event has resolved and anticoagulation is stable.

reducesLiver disease

Antithrombin is synthesised in the liver, so cirrhosis or acute hepatic failure reduces production and lowers circulating antigen independent of hereditary deficiency.

reducesNephrotic syndrome

Urinary protein loss includes antithrombin, which is small enough to cross a damaged glomerular filter; heavy proteinuria can reduce levels substantially.

reducesOestrogen therapy and pregnancy

Oestrogen and the hormonal milieu of pregnancy lower antithrombin modestly, so borderline results may require repeat testing off hormones or postpartum for accurate classification.

variableSample handling and storage

Antithrombin is stable in citrated plasma when processed promptly and refrigerated; delayed separation or prolonged storage at room temperature can degrade the protein and yield falsely low results.

What do Antithrombin III Antigen results mean?

Elevated

Elevated antithrombin is uncommon and usually not clinically significant. It may be seen transiently after warfarin initiation (as other vitamin-K-dependent factors fall) or with acute-phase reactions, but high levels do not alter thrombotic or bleeding risk materially.

Normal

A normal antithrombin antigen level makes hereditary type I deficiency unlikely but does not exclude type II (functional) deficiency; pair with an activity assay if clinical suspicion remains high. Normal results during acute thrombosis or on heparin should be repeated when the patient is stable and off anticoagulation.

Reduced

Antithrombin III deficiency below 70% suggests hereditary deficiency (type I if antigen and activity both low, type II if activity disproportionately reduced) or acquired deficiency from heparin, acute thrombosis, DIC, liver disease, nephrotic syndrome, or L-asparaginase chemotherapy. Hereditary deficiency is autosomal dominant with high penetrance and warrants family screening; homozygous deficiency is rare, life-threatening, and presents in the neonatal period. Acquired deficiency usually resolves when the underlying condition improves but may necessitate antithrombin concentrate during acute thrombosis or surgery.

Note: Antithrombin testing must be timed carefully — avoid during acute thrombosis, heparin therapy, or pregnancy unless the clinical question specifically concerns acquired deficiency. A single low result requires confirmation on a second occasion, off anticoagulation and when the patient is well, before diagnosing hereditary deficiency. Always interpret alongside protein C, protein S, and genetic thrombophilia markers, as multiple defects can coexist and compound risk.

Frequently asked questions

The antigen assay measures the quantity of antithrombin protein, while the activity assay measures its functional ability to inhibit thrombin. Type I deficiency shows low antigen and low activity; type II (rarer) shows normal antigen but reduced activity due to a dysfunctional protein.

How to access the Antithrombin III Antigen test

The Antithrombin III Antigen reference page is free and open to all practitioners. Create a free practitioner account to see pricing, save tests to your list, and generate requisition forms. Verification takes 1–2 business days.

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About this page

Published: October 7, 2026

Last reviewed: October 7, 2026

References:

Bauer KA. Approach to thrombophilia. UpToDate topic review. (2025)
British Committee for Standards in Haematology. Investigation and management of heritable thrombophilia. Br J Haematol. (2010)
American College of Medical Genetics and Genomics. Evaluation of genomic applications in practice and prevention (EGAPP) — hereditary thrombophilia testing. (2011)
Patnaik MM, Moll S. Inherited antithrombin deficiency: a review. Haemophilia. (2008)

This content is for licensed healthcare practitioners only and does not constitute medical advice. Clinical decisions should be based on the full clinical picture and not on any single test result.