The recommended therapy for patients with unstable angina with high-risk markers or non-ST-elevation MI includes heparin anticoagulation and the use of tirofiban or eptifibatide in addition to aspirin, with the possible addition of clopidogrel.31The differential diagnosis of thrombocytopenia in this population, therefore, is similar to that already discussed for thrombocytopenia after PCI. Possibly due to the longer duration of treatment, the incidence of thrombocytopenia is higher in patients with ACSs than in those undergoing PCI,32 and the incidence of thrombocytopenia in patients treated with a GPIIb/IIIa inhibitor is somewhat higher than those treated without these drugs.19,32–34 Despite the move toward early intervention in patients with ACSs, the hospital stay and exposure to drugs that may cause thrombocytopenia is not short. The median length of stay in the early intervention arm of the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction (TACTICS-TIMI) 18 trial35was 3.9 days. Therefore, it is possible that the timing of thrombocytopenia may lead to the inclusion of therapy with GPIIIb/IIIa inhibitors, heparin, and clopidogrel in the differential diagnosis. Diagnosis and management decisions regarding the GPIIIb/IIIa inhibitors and clopidogrel are the same as those made around the time of PCI. If HIT is a concern, all heparin therapy must be discontinued and alternative anticoagulation therapy should be started, not only to prevent thrombosis associated with HIT, but also to manage the underlying coronary disease. Lepirudin, which has been approved for the treatment of HIT, has been evaluated in patients with ACSs in a series of large randomized trials.36 Combined data from the OASIS-1 and Organization to Assess Strategies for Ischemic Syndromes (OASIS)-2 trials demonstrated a 14% reduction of MI or death at 35 days in the lepirudin arm (0.15 mg/kg/h, adjusted to the activated partial thromboplastin time) when compared to the heparin control arm. Argatroban, also approved for the treatment of HIT, has not been evaluated in trials of ACSs alone, but a significant proportion of the population in the trials that led to the approval of argatroban (2 μg/kg/min, adjusted to the activated partial thromboplastin time. The initial dose was reduced in patients with hepatic impairment) had circulatory disease.11 While there are limited data for the use of bivalirudin in patients with ACSs37–38 outside of PCI, an infusion dose has not been defined.