When should antithrombin activity be tested?

Test at least three months after an acute venous thromboembolic event and off heparin for at least two weeks. Testing during or immediately after thrombosis, on heparin, or during acute illness yields uninterpretable results because antithrombin is consumed by clotting and degraded during inflammation.

Can a patient on heparin be tested for antithrombin deficiency?

No. Heparin accelerates antithrombin consumption and lowers activity independently of any inherited defect. Stop heparin for at least two weeks or switch to warfarin or a direct oral anticoagulant before testing.

Is fasting required for the antithrombin activity test?

No. Antithrombin activity does not require fasting, though the specimen must be collected into a sodium citrate tube filled to the correct level and processed promptly.

What is the difference between antithrombin activity and antigen?

Activity assays measure the functional capacity of antithrombin to inhibit thrombin or factor Xa and detect both quantitative (type I) and qualitative (type II) defects. Antigen assays measure the protein concentration and miss type II defects, so functional activity is the preferred initial test.

How is inherited antithrombin deficiency managed?

Heterozygous inherited deficiency confers high thrombotic risk and typically warrants long-term anticoagulation after a first unprovoked event. Pregnancy and the puerperium require intensified thromboprophylaxis. Homozygous deficiency is rare and presents catastrophically in the neonatal period, requiring antithrombin concentrate replacement.

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Antithrombin III Activity

Q: What does low antithrombin activity indicate?

Low activity suggests antithrombin deficiency, which may be inherited (type I quantitative or type II qualitative) or acquired. Acquired causes include acute thrombosis, heparin therapy, disseminated intravascular coagulation, sepsis, nephrotic syndrome, and liver disease. A repeat sample off anticoagulation and outside acute illness is required to confirm inherited deficiency.

Q: Does liver disease affect antithrombin levels?

Yes. Antithrombin is synthesised in the liver, so cirrhosis and acute liver failure reduce its production. A low result in the setting of deranged liver biochemistry does not indicate an inherited thrombophilia and should not trigger family screening.

The Antithrombin III Activity test measures the functional capacity of antithrombin, a liver-synthesised serine protease inhibitor that irreversibly inactivates thrombin and factor Xa. Inherited or acquired deficiency predisposes to venous thromboembolism;

Biomarkers

Blood (plasma)

Sample

3–5 business days

Turnaround

Fasting

What is the Antithrombin Activity test?

The Antithrombin III Activity test measures the functional capacity of antithrombin, the liver-synthesised serine protease inhibitor that forms the central physiological counterbalance to the coagulation cascade. It is ordered as part of the thrombophilia screen when a venous thromboembolic event occurs in the absence of obvious provocation, recurs despite adequate treatment, presents in an unusual site — mesenteric, cerebral, or portal vein — or clusters in a family, particularly when the index case is young. Because antithrombin is consumed in the acute phase of thrombosis, depleted by heparin, reduced by liver disease and nephrotic syndrome, and lowered by the acute-phase response of critical illness, the test must be timed carefully. Practitioners order it after acute anticoagulation has been completed or at least three months after an event, and interpret a single low value in light of hepatic function, renal protein loss, inflammatory markers, and medication history before concluding that an inherited deficiency is present. A functional activity assay is preferred to antigen measurement because it detects both quantitative and qualitative defects.

What does the Antithrombin Activity test measure?

AT III(Antithrombin III Activity)

Range: Approximately 80–120% of normal pooled plasma activity; neonatal and paediatric ranges differ.Optimal: Activity consistently above 80% is typical in healthy adults; values below 50–60% confer higher thrombotic risk, though clinical penetrance of inherited deficiency is incomplete and influenced by additional risk factors.%

Antithrombin is a serine protease inhibitor synthesised in the liver that irreversibly inhibits thrombin, factor Xa, and several other clotting enzymes, forming the principal physiological brake on the coagulation cascade. Heparin potentiates its activity by three orders of magnitude, which is the basis of heparin anticoagulation. Functional activity assays measure the rate at which a patient's plasma inhibits a standardised amount of thrombin or factor Xa, reflecting both the concentration of the protein and the integrity of its active site. Because antithrombin is consumed during thrombosis and degraded by elastase released from activated neutrophils, acute illness can transiently lower activity independently of an inherited defect.

Antithrombin deficiency — either inherited or acquired — predisposes to venous thromboembolism and is one of the classical thrombophilias investigated after unprovoked or recurrent clots, particularly in younger patients or those with a family history. Inherited deficiency is autosomal dominant and divided into type I (quantitative reduction) and type II (dysfunctional protein), though the activity assay used clinically captures both. Acquired deficiency accompanies sepsis, disseminated intravascular coagulation, nephrotic syndrome, liver disease, and heparin therapy, all of which must be excluded before attributing a low result to a hereditary cause. Serial testing off anticoagulation and outside the acute event is essential for reliable interpretation.

Why is the Antithrombin Activity test ordered?

Investigation of unprovoked venous thromboembolism in patients younger than 50 years, especially when there is no acquired trigger such as surgery, immobilisation, or oestrogen therapy
Recurrent venous thrombosis despite adequate anticoagulation or unusually severe clot burden at first presentation
Thrombosis in atypical sites — cerebral, mesenteric, portal, or hepatic veins — which raises suspicion of an underlying thrombophilia
Strong family history of venous thromboembolism, particularly when multiple first-degree relatives are affected or events occur at a young age
Neonatal purpura fulminans or large-vessel thrombosis in infancy, where homozygous or compound heterozygous antithrombin deficiency may present catastrophically
Heparin resistance during therapeutic anticoagulation, as very low antithrombin activity blunts the response to unfractionated heparin
Pre-conception counselling in women with known or suspected inherited thrombophilia, to guide anticoagulation strategy during pregnancy and the puerperium
Monitoring antithrombin levels in patients with nephrotic syndrome, sepsis, or disseminated intravascular coagulation when replacement therapy is being considered

Sample collection and turnaround

Sample type

Blood (plasma)

Fasting required

Collection method

Venipuncture at patient service centre

Turnaround

3–5 business days

Collection notes

Phlebotomy via Quest Diagnostics patient service centre. Collect into sodium citrate (blue-top tube), fill to the marked level to achieve correct anticoagulant ratio, and mix gently by inversion. Avoid haemolysis and ensure the specimen reaches the laboratory within the stability window. Ideally collect at least three months after an acute thrombotic event and off heparin for at least two weeks; patients may remain on warfarin or direct oral anticoagulants, though warfarin modestly raises antithrombin. Record any anticoagulant therapy and timing relative to the acute event on the request form.

Specimen requirements

Minimum 2.7 mL citrated plasma (0.109 M sodium citrate, 9:1 blood-to-anticoagulant ratio). Separate plasma within four hours of collection and refrigerate or freeze if not analysed immediately. Rejected if clotted, under-filled, haemolysed, or collected into the wrong anticoagulant.

What can affect Antithrombin Activity results?

reducesHeparin and heparin-like anticoagulants

Unfractionated and low-molecular-weight heparins bind antithrombin and accelerate its consumption; patients on heparin often show low activity that does not reflect baseline status, so testing should be deferred until anticoagulation is stopped or switched to a direct oral anticoagulant for at least two weeks.

reducesAcute thrombosis and the acute-phase response

Antithrombin is consumed at the site of clot formation and degraded by neutrophil elastase during systemic inflammation, so activity falls transiently during and immediately after a thrombotic event or sepsis; repeat testing at least three months later is required to distinguish inherited from acquired deficiency.

reducesLiver disease

Because antithrombin is synthesised in the liver, cirrhosis and acute liver failure reduce its production; a low result in the setting of deranged liver biochemistry does not indicate an inherited thrombophilia.

reducesNephrotic syndrome and protein-losing enteropathy

Urinary or enteric loss of proteins, including antithrombin, lowers plasma activity; check urinary protein excretion and serum albumin before attributing a low value to a hereditary cause.

variableOestrogen therapy and pregnancy

Oral contraceptives and hormone replacement may modestly lower antithrombin, and pregnancy itself is a hypercoagulable state; testing is best performed outside these contexts unless clinically urgent.

variableSample handling and storage

Antithrombin activity is stable in citrated plasma for several hours at room temperature and days refrigerated, but prolonged delays or freeze–thaw cycles can degrade activity; specimens collected into the wrong anticoagulant or clotted samples yield unreliable results.

What do Antithrombin Activity results mean?

Elevated

Elevated antithrombin activity is rare and not clinically significant; it may be seen with warfarin therapy, which raises antithrombin slightly, but has no recognised association with bleeding or other pathology.

Normal

Activity between 80% and 120% is the usual adult range and does not support a diagnosis of antithrombin deficiency. A normal result does not exclude other thrombophilias — factor V Leiden, prothrombin G20210A, protein C or S deficiency — so the broader thrombophilia panel is interpreted as a whole rather than on the basis of antithrombin alone.

Reduced

Low activity — typically below 80% and often below 50–60% in inherited deficiency — raises suspicion of antithrombin deficiency, which may be inherited (type I quantitative or type II qualitative) or acquired. Acquired causes include acute thrombosis, heparin therapy, disseminated intravascular coagulation, sepsis, nephrotic syndrome, liver disease, and large surgical procedures. Confirm with a repeat sample collected at least three months after the acute event, off heparin, and with normal hepatic and renal function. If the deficiency persists, family screening and genetic counselling are indicated. Inherited antithrombin deficiency confers high thrombotic risk — up to ten-fold for heterozygotes — and influences decisions about duration and intensity of anticoagulation, particularly in pregnancy.

Note: Timing is everything: testing during or soon after acute thrombosis, on heparin, or in the setting of acute illness or nephrotic syndrome yields uninterpretable results. A single low value must be confirmed on a second occasion, ideally off all anticoagulation except warfarin or a direct oral anticoagulant and with normal liver and kidney function, before concluding that an inherited deficiency is present. Neonatal and paediatric reference ranges are lower than adult values, and antithrombin rises to adult levels over the first few months of life. Assay methods differ — chromogenic and clot-based — and reference intervals are laboratory-specific.

Frequently asked questions

Antithrombin is a serine protease inhibitor synthesised in the liver that irreversibly inactivates thrombin, factor Xa, and other clotting enzymes, forming the principal physiological brake on the coagulation cascade. Heparin potentiates its activity, which is the basis of heparin anticoagulation.

How to access the Antithrombin Activity test

The Antithrombin Activity 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:

Patnaik MM, et al. The role of antithrombin deficiency in venous thromboembolism. Mayo Clin Proc. (2012)
American Society of Hematology guidelines for management of venous thromboembolism: thrombophilia testing. (2018)
British Committee for Standards in Haematology: investigation and management of heritable thrombophilia. (2010)
Mahmoodi BK, et al. Association of antithrombin deficiency with venous thromboembolism: a systematic review and meta-analysis. Thromb Haemost. (2011)

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.