Great discrepancy in antithrombin activity measured using five commercially available functional assays

Congenital antithrombin (AT) deficiency is an inherited thrombophilia with high thrombosis prevalence. It has been reported that functional laboratory tests have varying potential in recognizing type II defects, and that there is discrepancy between thrombin inhibition based and factor Xa inhibition based methods.

Patients with known AT deficiency (n=374) were interviewed and their current AT status was tested in a new blood sample (n=214). The samples were analyzed using five different commercial methods (either thrombin or FXa based and one thrombin based method using two different incubation times). Antigen assay was used for typing the deficiency.

In 101 of 214 (47.2%) samples the results obtained by different methods were congruent: 91 low and 10 normal by all assays. All other 113 (52.8%) samples showed discrepant values between the assays: most of them had abnormal results by two methods and normal by other methods. The discrepancies were observed mainly in type II deficiency. The best correlation of results was observed between one thrombin based and one FXa based assay.

There was great inter-assay variability especially in type II deficient patients, but also in patients with type I deficiency. However, most of the patients defined as having normal AT activity by some methods had thrombotic symptoms. Most tested assays find type I AT deficient patients accurately. In our study population only methods A1 and C could find most patients with type II AT deficiency, whereas methods A2, B and D misdiagnosed the majority of patients as non-deficient.