Variability of Argatroban Effects on the Multiple APTT Reagents in High and Low Coagulation Activity Samples

Argatroban is routinely monitored using activated partial thromboplastin time (APTT), with a recommended target range of 1.5-3.0 times. Although this range was established based on clinical trial data, including several APTT reagents, the differences in reactivity among APTT reagents remain unclear. This study compared the reactivity of six commercial APTT reagents to argatroban in normal and abnormal plasma samples.

Normal samples were spiked with argatroban and five abnormal samples: low coagulation factor activity, high factor VIII, high factor VIIa, low fibrinogen, and high fibrinogen. Drug concentrations were adjusted to 0, 0.5, 1.0, 1.5, and 2.0 μg/mL in each plasma. Six APTT reagents, including silica or ellagic acid activator and phospholipids derived from synthetic or natural sources, were tested.

The APTT ratio range among the six reagents was 2.4-3.2 in normal plasma at a concentration of 2.0 μg/mL. The sample showing the most expanded range was low coagulation activity (3.3-5.2), and the range in the sample with high factor VIII activity decreased (1.5-2.2).

A reactivity difference was observed in argatroban-spiked samples, which increased in abnormal plasma samples. APTT may not reflect the anticoagulant activity of argatroban in patients with abnormal coagulation activity. The reactivity of APTT should be confirmed in each laboratory, and patient background coagulation status should be assessed before monitoring is conducted using the APTT ratio.