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Heparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin products, but not warfarin. HIT usually occurs 5‒10 days after exposure to heparin. Here, we report a case of HIT with multiple thrombotic events and severe thrombocytopenia resulting from intermittent intravenous heparin flushes for maintenance of a newly placed subclavian central venous catheter (CVC) for stem cell transplant. The patient is a woman in her forties with multiple myeloma who presented to the emergency department (ED) with dyspnea, pleuritic-type chest pain, hemoptysis, and worsening left-leg swelling. Heparin had been used to flush the CVC. Her platelet count began dropping approximately one week after insertion. The patient was receiving other medications known to cause thrombocytopenia. She had undergone multiple platelet transfusions. In the ED, her lab results showed thrombocytopenia), anemia; renal insufficiency; and elevated troponin, prothrombin time, and D-dimer levels. Because of the hemoptysis and thrombocytopenia, she initially received platelet transfusion and oxygen. She was found to have deep vein thrombosis of the lower extremity and started a referral to interventional radiology for inferior vena cava (IVC) filter placement. However, further review and consultation of the Benign Hematology service, discussion about the timing of decreased platelet count shortly after CVC placement and heparin administration, and the presence of thrombosis, suggested a high pre-test probability of HIT. Anticoagulation with argatroban was initiated, and IVC filter insertion was canceled. Further workup confirmed HIT diagnosis and saddle pulmonary embolism. During the patient's hospitalization, her platelets continued to improve and reached baseline upon discharge. She was transitioned to fondaparinux at the time of discharge. A few weeks later, she had successful stem cell transplantation. Emergency physicians treating patients with thrombocytopenia receiving heparin, even in small amounts, should consider the possibility of HIT and be familiar with its management., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Thein et al.)