Thrombotic microangiopathy (TMA) is a term used for a group of rare and life-threatening hematological conditions. Usually, these disease processes are characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and microthrombi leading to tissue or organ injury. We present a case of a 41-year-old male with TMA induced by uncontrolled hypertension leading to end-stage renal disease requiring hemodialysis. Our goal is to highlight the importance of distinguishing hypertension-induced thrombotic microangiopathy from other etiologies of TMA, particularly thrombotic thrombocytopenic purpura (TTP), and its effect on renal function despite treatment focused on blood pressure control. Thus, it is a challenging diagnosis for clinicians to determine whether to initiate plasmapheresis for prompt treatment of suspected TTP in the setting of severe hypertension with thrombocytopenia.