Antithrombin III

Antithrombin is a natural anticoagulant that inhibits the activated coagulation factors thrombin (factor IIa), factor Xa, and, to a lesser extent, factor XIa and factor IXa.

Normal findings

Antithrombin activity ^[1] :

• Newborn: 35-40%
• Older than 6 months to adult: 80-130%

Antithrombin antigen assay ^[1] :

• Plasma: > 50% of control value
• Serum: 15-34% lower than plasma value
• Immunologic: 17-30 mg/dL
• Functional: 80-120%

Variation in values occurs according to the laboratory methods employed. ^[1]

An increased antithrombin level is not a clinical problem.

Inherited types of antithrombin deficiency are as follows:

• Type I - Decreased functional and immunological antithrombin level

• Type II - Decreased functional antithrombin activity, while protein concentration is normal

Acquired antithrombin deficiency may be associated with the following:

• Disseminated intravascular coagulation

• Unfractionated heparin therapy

• Liver disease

• Nephrotic syndrome

• Protein-losing condition

• Estrogen therapy

• L-asparaginase treatment

• Cardiac surgery

Specimen: Citrated plasma

Collection: Blue-top tube with 3.2% sodium citrate

Centrifugation: 2000-2500 g for 15 minutes or similar regimen to produce platelet-poor plasma

Storage: Up to 8 hours at room temperature; plasma sample should be frozen within 1-2 hours; specimen is stable for one month at -20°C or 6-9 months at -80°C

Antithrombin activity is measured by synthetic chromogenic activity in the presence of excess heparin levels.

A high concentration of hemoglobin, bilirubin, and triglycerides might affect antithrombin measurement.

Treatment with thrombin inhibitors may lead to overestimation of the antithrombin level in plasma.

Description

Antithrombin is glycoprotein (molecular weight, 58 kDa) that is synthesized in the liver. It circulates in the blood, with a half-life of 2-3 days.

Antithrombin is a natural anticoagulant that inhibits the activated coagulation factors thrombin (factor IIa), factor Xa, and, to a lesser extent, factor XIa and factor IXa. Heparin significantly increases the inhibition rate.

The antithrombin level does not influence the results of screening coagulation tests such as partial thromboplastin time (PTT), prothrombin time (PT), and thrombin time. The measurement of antithrombin activity (functional antithrombin level) is a widely used laboratory test in clinical practice, while the antithrombin antigen (immunological antithrombin level) assay, which is used to confirm inherited antithrombin deficiency only, is rarely used.

Indications/Applications

Antithrombin testing is indicated in the following: ^[2]

• Idiopathic thromboembolic disease as a part of thrombophilia workup with other hemostasis tests such as protein C, protein S, homocysteine, lupus anticoagulant, factor V Leiden, and prothrombin mutation 20210

• Monitoring of antithrombin substitution therapy in the treatment of inherited or acquired antithrombin deficiency

• Resistance of unfractionated heparin therapy ^[3]

Considerations

Inherited antithrombin deficiency is less common than acquired deficiency. ^[4] The diagnosis of hereditary deficiency requires testing of both antithrombin activity and antithrombin antigen, and repeated testing and family studies may be needed.

Antithrombin deficiency can increase the risk of recurrent miscarriage. ^[5]

Administration of full-dose unfractionated heparin (but not LMWH) can cause a reversible reduction in antithrombin levels of up to 30% within several days. A falsely normal antithrombin concentration might be determined in antithrombin-deficient patients treated with thrombin inhibitors, but not with anti-Xa inhibitors. ^[6]

While most functional laboratory assays are sensitive for detecting antithrombin deficiency type I, some commercial assays are better than others at detecting antithrombin deficiency type II. ^{[7, 8]}