Anemia is the most prevalent form of anemia in children throughout the world and often is left undiagnosed or is not followed up and other treatable or serious anemia possibly responsible for the symptoms is not identified.

Objective is to review the common problems in diagnosing and failing to diagnose (or delay the diagnosis) of non–iron-deficiency causes of pediatric anemia, and to suggest a logical, practical diagnostic strategy for the clinic.

A bibliographic and web-based database search was performed to review the literature, clinical practice guidelines (World Health Organization, American Academy of Pediatrics, European Society for Pediatric Gastroenterology, Hepatology and Nutrition, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition), and case reports on etiology of pediatric anemia, laboratory evaluation, and diagnostic delay.

Non–iron-deficiency anemia in children can be due to hemoglobinopathies (thalassemia trait, sickle cell disease), red cell membrane and enzyme disorders (hereditary spherocytosis, glucose-6-phosphate dehydrogenase [G6PD] deficiency), inherited bone marrow failure syndromes (Diamond-Blackfan anemia), nutritional deficiencies (vitamin B12, folate), anemia of chronic disease/inflammation, celiac disease, lead poisoning, chronic kidney disease, transient erythroblastopenia of childhood, hemolytic and immune-mediated anemia, or marrow-infiltrative disorders like leukemia. Common errors that lead to delayed diagnosis include reliance on hemoglobin level alone for diagnosis of iron deficiency, diagnostic anchoring for iron deficiency, empirical iron treatment trials without peripheral smear review or ferritin or reticulocyte testing, and lack of family history.

Children with anemia not secondary to iron deficiency can benefit significantly from a step-wise approach, avoiding empirical treatment with iron, based on red cell indices, reticulocyte count, peripheral smear examination and additional second-line testing where necessary.