Diagnosis and management of hereditary hemolytic anemia in Korea

Hereditary hemolytic anemia (HHA) is a group of inherited disorders characterized by a shortened red blood cell (RBC) lifespan due to intrinsic defects involving the RBC membrane, cytoskeleton, hemoglobin, or metabolic enzymes. Traditionally, membranopathies have been the most common type of HHA in Korea, whereas hemoglobinopathies have been rare. The epidemiology of HHA has recently changed in Korea because of changes in population dynamics owing to an increase in international marriages and immigration. Accurate diagnosis is essential for appropriate management because therapeutic responses differ among HHA subtypes. The initial evaluation begins with the confirmation of hemolysis and exclusion of immune-mediated or microangiopathic processes. The diagnostic process integrates RBC indices, reticulocyte responses, and peripheral blood smears (PBS), supplemented by specialized assays. The eosin-5-maleimide binding test and osmotic fragility tests are valuable for detecting hereditary spherocytosis (HS), whereas osmotic gradient ektacytometry and membrane protein analysis provide comprehensive assessments of membranopathies. PBS can provide initial insights into hemoglobinopathies. Enzymopathies usually result in nonspecific normocytic hemolytic anemia, and sequential enzyme activity and genetic testing are recommended. When phenotypic evaluation is limited, multigene sequencing panels allow for the precise identification of pathogenic variants, substantially improving diagnostic accuracy. Management strategies depend on the patient’s specific diagnosis. Although splenectomy is effective for various HHA types, such as HS, pyruvate kinase deficiency, thalassemia, and selected cases of hereditary elliptocytosis, it provides little benefit and carries a significant risk in patients with hereditary stomatocytosis, hereditary xerocytosis, and congenital dyserythropoietic anemia type I. Therefore, accurate diagnosis before making a surgical decision is crucial. As genetic insights refine diagnostic pathways and targeted therapies such as pyruvate kinase activators emerge, individualized management strategies remain central to optimizing outcomes in patients with HHA.