In severe heart failure with hemodynamic failure, when inotropic therapies no longer suffice (INTERMACS [Interagency Registry for Mechanically Assisted Circulatory Support] 1), temporary mechanical support is used as a bridging measure until a more definitive treatment, such as a left ventricular assist device, a total artificial heart or transplantation, is performed. Due to shear stress during the passage of blood through the pump, limited hemolysis is to be expected. We describe the case of a 37-year-old patient with terminal heart failure who suffered severe hemolysis during treatment with temporary mechanical support. Examination of the cardiac apex after left ventricular assist device implantation revealed a poorly differentiated tumor. Histopathologic examination revealed underlying extramedullary hematopoiesis, triggered by severe hemolytic anemia. Following exclusion of neoplasia, the patient subsequently underwent heart transplantation. Post-transplantation, the patient was diagnosed with alpha-thalassemia and heterozygote hemoglobin E. This combination can result in mild thalassemia with chronic low-level hemolysis and mild anemia, probably severely exacerbated in the presence of high-shear stress.