Thrombin-Based Antithrombin Assays Show Overestimation of Antithrombin III Activity in Patients on Heparin Therapy due to Heparin Cofactor II Influence^[*]

Summary

An extensive comparison has been performed on the clinical chemistry automate Hitachi 717 between thrombin-and Factor X_a-based methods for determination of antithrombin III activity. In 460 patients who did not receive any heparin therapy the agreement between assays was in general close although the thrombin-based methods resulted in slightly higher assignments of 0.3—2.6% antithrombin III activity. The discrepancy was, however, substantial in plasmas from patients receiving heparin of >20000 IU/day, resulting in plasma levels of heparin of 0.8-1.2 IU/ml. Thus, analysis of 102 patients showed that the thrombin-based methods resulted in, on average, 7-16% higher assignment of antithrombin III activity as compared to the Factor X_a-based method used.

Addition of antibodies to antithrombin III and heparin cofactor II revealed that the discrepancy was primarily due to contribution of heparin cofactor II activity in the thrombin-based methods. The results thus suggest that the Factor X_a-based antithrombin III activity method provides more valid results in patients on heparin therapy.

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