Direct Thrombin Inhibitors: Use and Consequences in Patients with Heparin-Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is an immunologic response to heparin exposure that may lead to thrombosis. Argatroban and bivalirudin are two commonly used direct thrombin inhibitors (DTIs) for the prevention of thrombosis in patients with HIT. However, DTIs may lead to major bleeding events. Data on the use and consequences of DTIs is limited. Of note, patients with suspected HIT are of interest in the thesis, as current guidelines recommend the initiation of DTI treatment at the time of clinical suspicion of HIT. This thesis focused on the identification of suspected HIT, and the use and consequences of direct thrombin inhibitors (DTI) for the treatment of suspected HIT. First, algorithms based on diagnostic codes, medications and diagnostic tests were developed and validated to identify patients with suspected HIT. An algorithm based only on the timing of medication and diagnostic tests was recommended for the identification of suspected HIT from claims data, as it was observed to have the highest positive predictive value and sensitivity. Second, the rates of thrombosis, major bleeding, amputation and mortality were compared between argatroban-treated and bivalirudin-treated patients using administrative claims data obtained from the University HealthSystem Consortium. The difference in the likelihood of thrombosis, amputation and mortality between the two DTI groups was not statistically significant. However, bivalirudin-treated patients were more likely to experience major bleeding than argatroban-treated patients. Third, the use of bivalirudin for the treatment of suspected HIT (off-label use) increased from one-third to half of DTI-treated patients from 2010 to 2012. Patients treated by surgeons or specialists were more likely to receive off-label bivalirudin compared to patients treated by primary care. In addition, hepatic impairment and skin infection increased the odds of patients to receive bivalirudin over argatroban. In conclusion, the off-label use of bivalirudin should be scrutinized for medical necessity due to the higher risk of bleeding than argatroban, except in patients with hepatic impairment.