How is Antithrombin III deficiency diagnosed?

Diagnosis of Antithrombin III Deficiency

Antithrombin III (AT III) deficiency is a rare genetic disorder that affects the body's ability to regulate blood clotting. It is important to diagnose this condition early as it can lead to an increased risk of developing blood clots, which can be life-threatening. The diagnosis of AT III deficiency involves a combination of clinical evaluation, laboratory tests, and genetic analysis.

Clinical Evaluation

The first step in diagnosing AT III deficiency is a thorough clinical evaluation. The healthcare provider will review the patient's medical history, including any family history of blood clotting disorders. They will also assess the patient's symptoms, which may include recurrent blood clots, deep vein thrombosis (DVT), pulmonary embolism, or a history of pregnancy complications.

Laboratory Tests

Several laboratory tests are used to diagnose AT III deficiency. These tests measure the level and activity of antithrombin III in the blood. The most commonly used tests include:

• Antithrombin III Antigen Assay: This test measures the level of antithrombin III protein in the blood. A low level of antithrombin III may indicate a deficiency.


• Antithrombin III Functional Assay: This test measures the activity of antithrombin III in the blood. A reduced activity level suggests a deficiency.


• Thrombin Time Test: This test measures the time it takes for a blood clot to form in the presence of thrombin. A prolonged thrombin time may indicate a deficiency.


• Activated Partial Thromboplastin Time (aPTT) Test: This test measures the time it takes for blood to clot. A prolonged aPTT may suggest a deficiency.

In some cases, additional tests may be performed to rule out other causes of blood clotting disorders, such as factor V Leiden mutation or protein C deficiency.

Genetic Analysis

Genetic analysis is the most definitive method for diagnosing AT III deficiency. It involves testing for specific mutations in the SERPINC1 gene, which provides instructions for producing antithrombin III. This test can identify the specific genetic mutation responsible for the deficiency.

Genetic analysis is particularly useful in cases where the laboratory tests are inconclusive or when there is a strong suspicion of AT III deficiency based on the clinical presentation. It can also be used for family members of individuals with a known AT III deficiency to determine their risk of inheriting the condition.

Other Considerations

It is important to note that the diagnosis of AT III deficiency can be challenging due to its rarity and the variability of symptoms. In some cases, individuals may have a mild deficiency that is not easily detected by laboratory tests. Additionally, certain factors such as pregnancy, oral contraceptive use, or acute illness can affect the accuracy of the test results.

If AT III deficiency is suspected but the initial tests are inconclusive, further testing and consultation with a hematologist or a specialist in blood clotting disorders may be necessary. Genetic counseling may also be recommended to discuss the implications of the diagnosis and the risk of passing the condition to future generations.

In conclusion, the diagnosis of Antithrombin III deficiency involves a combination of clinical evaluation, laboratory tests, and genetic analysis. Clinical evaluation helps assess the patient's symptoms and medical history, while laboratory tests measure the level and activity of antithrombin III in the blood. Genetic analysis is the most definitive method for diagnosing AT III deficiency and involves testing for specific mutations in the SERPINC1 gene. It is important to consult with healthcare professionals and specialists in blood clotting disorders for accurate diagnosis and appropriate management of AT III deficiency.