Management of patients with acute heparin-induced thrombocytopenia (HIT) with cavo-atrial renal cancer requiring surgery on cardiopulmonary bypass (CPB) and possible deep hypothermia circulatory arrest is a challenge. A staged approach using Bivalirudin, plasmapheresis, and intravenous immunoglobulin (IVIG) was used to preoperatively de-escalate HIT guided by enzyme-linked immunosorbent assay (ELISA) and serotonin release assay (SRA). Intraoperatively heparin was used as the anticoagulant for CPB as DHCA was likely to be used to remove the atrio-caval tumor. Heparin is effective in preventing clots in the circuit during DHCA. To prevent HIT upon re-exposure to heparin during CPB, a bolus of a Cangrelor (reversible P2Y12 platelet receptor inhibitor) was given before heparin and during CPB whilst platelet activity was monitored using platelet reactivity units (PRU). Postoperatively, to prevent recurrence of HIT, plasmapheresis was used until SRA and optical density (OD) resulted. The patient had a successful outcome.