a thorough yet focused history, performing a detailed physical examination, and ordering appropriate laboratory investigations The history should focus on several major components First, particular attention should be paid to the rapidity of onset of pallor The slow development of pallor suggests diminished red cell production, as is found in bone marrow aplasia or iron deficiency However, the acute onset of pallor is consistent with the brisk hemolysis of autoimmune hemolytic anemia, the splenic sequestration of SCD, or rapid blood loss After establishing the time course of the anemia, the history can be directed toward categories of anemia or specific diseases A detailed dietary history, with particular attention to milk intake, is important in young children with suspected iron deficiency as excessive consumption of cow’s milk often results in iron deficiency Vitamin B12 deficiency may accompany strict vegetarian diets from which meat and egg products are excluded and may occur in breast-fed infants of vegetarian mothers or mothers with pernicious anemia Nutritional folic acid deficiency is rare and can usually be readily deduced from the presence of severe dietary alterations and evidence of other vitamin deficiencies The family history helps in the diagnosis of hemoglobinopathies and inherited disorders of red cell membranes and enzymes Because results of previous hemoglobin testing may have been explained inadequately or recalled inaccurately, a negative family history or newborn screening for hemoglobinopathies should not preclude evaluation of the patient’s hemoglobin phenotype if a sickling disorder is suspected The presence of a microcytic anemia unresponsive to iron in the parents suggests a thalassemic disorder A history of splenomegaly, splenectomy, or cholecystectomy in family members may help identify a hemolytic disorder such as hereditary spherocytosis or pyruvate kinase deficiency Finally, a well-directed review of systems is essential in looking for systemic disorders such as chronic renal disease, hypothyroidism, or JIA Pallor may be the presenting complaint in these and other disorders In the examination of the anemic patient, pulse and blood pressure (BP) should be measured to be sure hypovolemic shock and high-output cardiac failure are neither present nor imminent If anemia or volume loss is mild, tachycardia may be present with a preserved BP A systolic flow murmur is often heard if the hemoglobin level is below g/dL In the severely anemic patient, pallor of the skin and mucous membranes is usually readily apparent When anemia is less severe or when the skin color is dark, pallor may be appreciated only in the nail beds, palmar surfaces, lips, and palpebral conjunctiva Lymphadenopathy and splenomegaly may suggest a malignancy or an infectious disease such as