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Impella devices are percutaneously inserted ventricular assist devices which require a continuous purge solution that contains heparin to prevent pump thrombosis and device failure. We describe 2 patients with heparin-induced thrombocytopenia (HIT) supported with an Impella device utilizing an argatroban-based purge solution. Case 1 involved an 83-year-old female with biventricular failure which resulted in right ventricle Impella support. The purge solution was changed to include argatroban due to concern of device clotting in the setting of HIT. Case 2 involved a 55-year-old male with worsening cardiogenic shock which resulted in left ventricle Impella support. Due to decreased purge flow rates and concerns for clotting, argatroban was added to the purge solution. Both patients’ total argatroban regimens were monitored and adjusted by pharmacy, resulting in therapeutic anticoagulation without any major bleeding or thrombotic events. Subsequently, a protocol was designed and implemented. These case reports appear to demonstrate the safe and effective use of argatroban purge solutions for the necessary anticoagulation with an Impella device. Further studies are needed to confirm these results and determine the optimal dosing regimen.