Decrease of elevated thrombin–antithrombin (TAT) levels during lepirudin treatment.

Thrombin–antithrombin (TAT) levels as measured by ELISA were highly elevated in patients with acute HIT and ongoing thromboembolic complications (normal range, 1.0-4.1 μg/L), but normalized rapidly after the start of lepirudin treatment. The 25% and 75% quartiles and minimum and maximum values are given at the baseline (ie, up to 48 hours before the start of lepirudin), at 4 hours ± 2 hours, 12 hours ± 2 hours, 24 hours ± 6 hours, 36 hours ± 6 hours after the start of lepirudin, and then daily. Numbers of investigated patients at each time point are given at the top of the figure. The low number of patients at day 3 results from an overlap because 36 hours ± 6 hours was day 3 in those patients for whom treatment started late, at day 1, and values were counted only once. The small peak at day 3 was induced by patients receiving concomitant thrombolysis and, therefore, a reduced lepirudin dosage. These data underscore the prominent role of thrombin in acute HIT, provide a rationale for the use of a direct thrombin inhibitor in these patients, and indicate that in acute HIT thrombin generation is highest until day 4 to 5.