Appropriate management, as well as efficacy and safety, of
heparin-induced
thrombocytopenia (HIT) and prevention of severe consequences with
argatroban and
lepirudin are discussed.
Heparin-induced
thrombocytopenia, a serious immune-mediated
drug reaction, can occur as an isolated incident (isolated HIT) or with acute
thrombosis sometimes referred to as HIT and associated
thrombosis syndrome (HITTS). Due to the severe consequences associated with HIT, appropriate management is critical.
Argatroban and
lepirudin, two
direct thrombin inhibitors (DTIs), are currently FDA approved for use in patients with HIT. The clinical experience with these agents is critically examined in this article. The safety and efficacy of
argatroban in management of HIT were the subject of a single published clinical trial. The study was designed to reflect conventional clinical practice, whereby treatment of patients with HIT was initiated upon clinical suspicion. In several of these patients, HIT
antibodies could not be demonstrated. Compared to historical controls,
argatroban demonstrated efficacy in patients with isolated HIT; however, no differences were observed in HIT patients with acute
thrombosis. Rates of
bleeding episodes did not differ between
argatroban and control. The clinical efficacy and safety of
lepirudin have been the subject of three clinical trials and one large
drug monitoring program.
Lepirudin has demonstrated benefit in HIT patients with or without existing
thromboembolism.
Bleeding rates were higher than in the historical control. However, bleedings requiring transfusion did not differ. Although no direct head-to-head comparison trials of
argatroban and
lepirudin have been conducted, parallels can be drawn between the agents based on careful review of published clinical trials. Consistently, rates of new
thrombosis, limb
amputation, and death appear to be lower in patients treated with
lepirudin as compared with those treated with
argatroban, whereas the risk for major
bleeding per patient day seems to be similar with both DTIs.