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

Area of Science:

• Hematology
• Clinical Chemistry
• Thrombosis Research

Background:

• Congenital antithrombin (AT) deficiency is a genetic condition increasing the risk of blood clots (thrombosis).
• Existing functional laboratory tests show limitations in accurately identifying all types of AT deficiency, particularly Type II defects.
• Discrepancies exist between laboratory methods based on thrombin inhibition versus factor Xa inhibition.

Purpose of the Study:

• To evaluate the inter-assay variability of different commercial laboratory methods for detecting antithrombin deficiency.
• To assess the accuracy of these methods in identifying Type I and Type II antithrombin deficiencies.
• To determine the clinical relevance of discrepant results, especially in patients with thrombotic symptoms.

Main Methods:

• Analyzed 214 blood samples from patients with known antithrombin deficiency using five commercial assays (thrombin-based and FXa-based).
• Employed antigen assays for classifying the type of antithrombin deficiency.
• Compared results across different methods to identify congruence and discrepancies.

Main Results:

• Nearly half (47.2%) of samples yielded congruent results across all tested methods.
• Over half (52.8%) of samples showed discrepant results between assays, primarily in Type II deficiency cases.
• The best correlation was observed between specific thrombin-based and FXa-based assays.

Conclusions:

• Significant inter-assay variability exists in detecting antithrombin deficiency, particularly for Type II defects.
• Some assays misdiagnosed a majority of Type II deficient patients as non-deficient.
• Accurate laboratory testing is crucial, as patients with normal AT activity by some methods experienced thrombotic events.