85300
Antithrombin III; activity assay
CPT code 85300 describes the laboratory procedure for measuring the activity levels of Antithrombin III (ATIII), also known as Antithrombin. ATIII is a non-vitamin K-dependent glycoprotein produced by the liver that serves as a potent natural anticoagulant. It functions as a serine protease inhibitor that primarily inactivates thrombin (Factor IIa) and Factor Xa, and to a lesser extent, Factors IXa, XIa, and XIIa. The inhibitory action of ATIII is significantly accelerated (up to 1,000 to 10,000 times) in the presence of heparin or heparin-like glycosaminoglycans on the vascular endothelium. This assay is a functional test, meaning it measures how well the protein is performing its biological role in the coagulation cascade, rather than simply quantifying the amount of protein present (which is measured by the antigen assay, CPT 85301). Clinical testing for ATIII activity is essential in the evaluation of patients with suspected thrombophilia, recurrent venous thromboembolism (VTE), or a strong family history of clotting disorders. Deficiencies can be inherited (autosomal dominant) or acquired. Inherited deficiencies are categorized into Type I (reduced synthesis of normal protein) and Type II (normal levels of a dysfunctional protein). Because the activity assay detects both types of deficiencies, it is typically the preferred initial screening test. Acquired deficiencies are more common and can result from decreased production (liver disease), increased loss (nephrotic syndrome), or increased consumption (disseminated intravascular coagulation or major surgery). Proper interpretation of results requires consideration of the patient's current medication status, as certain anticoagulants like heparin can transiently decrease ATIII levels during therapy.
Clinical Indications
- Evaluation of patients with recurrent venous thromboembolism (VTE).
- Screening for hereditary thrombophilia in patients with a family history of early-onset thrombosis.
- Investigation of thrombosis occurring at unusual sites (e.g., mesenteric, splenic, or cerebral veins).
- Assessment of patients demonstrating heparin resistance, where higher than expected doses are required to achieve therapeutic anticoagulation.
- Monitoring and diagnosis of Disseminated Intravascular Coagulation (DIC).
- Evaluation of protein loss in patients with Nephrotic Syndrome.
- Assessment of synthetic liver function in patients with chronic liver disease or cirrhosis.
- Evaluation of neonatal thrombosis.
Procedure Steps
- Collection of venous blood into a vacuum tube containing 3.2% sodium citrate (light blue top).
- Centrifugation of the sample to obtain platelet-poor plasma.
- Addition of a known, excess amount of either thrombin or Factor Xa to the patient's plasma in the presence of heparin.
- Incubation of the mixture to allow the patient's endogenous Antithrombin III to inhibit the added enzyme.
- Introduction of a chromogenic substrate specific to the remaining (uninhibited) enzyme.
- Measurement of the rate of color change (absorbance) using a spectrophotometer.
- Calculation of the ATIII activity level, which is inversely proportional to the amount of residual enzyme activity and the intensity of the color produced.
- Comparison of the patient's result against a standard reference curve to report a percentage of normal activity.
Coding Guidelines
- Use 85300 for the functional/activity assay of Antithrombin III.
- Use 85301 for the quantitative/antigen assay of Antithrombin III. 85301 should not be reported if only the activity is measured.
- If both activity and antigen assays are performed, both codes may be reported, though medical necessity must support the use of both.
- Do not report 85300 as part of an automated hemogram; it is a specialized coagulation study.
- Check local coverage determinations (LCDs) for frequency limitations and specific covered diagnosis codes.
- When performed as part of a comprehensive thrombophilia panel, ensure all components are documented individually.