FIGURE 62.1 The diagnostic approach to pallor CBC, complete blood cell; WBC, white blood cell; PLT, platelet; RBC, red blood cell; MCV, mean corpuscular volume; G6PD, glucose-6phosphate dehydrogenase; DIC, disseminated intravascular coagulation; TEC, transient erythroblastopenia of childhood; HbSS, sickle cell anemia Numerous classifications of anemia have been used to assist the physician in the laboratory investigation of pallor Historically, the reticulocyte count and the MCV have been helpful measurements in categorizing causes of anemia The reticulocyte count can be performed rapidly and, as shown in Figure 62.1 , helps distinguish anemias caused by impaired red cell production (e.g., iron deficiency, hypoplastic anemia) from those caused by shortened red cell survival (e.g., hemoglobinopathies, membrane disorders, and other hemolytic states) The MCV provides a quick, accurate, and readily available method of distinguishing the microcytic anemias (iron deficiency, thalassemia syndromes) from the normocytic (membrane disorders, enzyme deficiencies, autoimmune hemolytic anemia, most hemoglobinopathies) or macrocytic (bone marrow/stem cell failure, disorders of B12 and folic acid absorption or metabolism) anemias The reticulocyte count and MCV should be interpreted with caution As shown in Figure 62.1 , disorders of shortened red cell survival are not always characterized by an increased reticulocyte count For example, reticulocytopenia may occur in autoimmune hemolytic anemia, despite active hemolysis and increased erythropoiesis in the bone marrow Chronic hemolytic disorders, such as sickle cell anemia or hereditary spherocytosis, may first be detected during an aplastic crisis when the reticulocyte count is low Unless the underlying disorder is recognized, the physician may be misled by this finding Furthermore, because the reticulocyte count is expressed as a percentage of total red cells, it must be indexed for the degree of anemia The easiest way to calculate the reticulocyte index is to multiply the reticulocyte count by the reported hemoglobin or hematocrit (HCT pt [patient]) divided by normal hemoglobin or hematocrit (HCT nl [normal]): For example, a reticulocyte count of 5% in a child with severe iron-deficiency anemia and a hematocrit of 6% are not elevated when corrected for the degree of anemia (5% × 6%/33% = 0.9%) The normal reticulocyte index is between 1.0 and 2.0 The MCV varies with age, necessitating the use of age-adjusted normal values ( Table 62.4 ) In addition, the measured MCV represents an average value If microcytic and macrocytic red cells are present in the peripheral blood as, for example, in a patient with combined iron deficiency and B12 deficiency, the MCV may remain normal Therefore, the peripheral smear should be examined carefully to determine whether the MCV reflects a single population of red cells of uniform size, or two or more populations of distinctly different size The red cell distribution width (RDW) is elevated in the presence of increased variation in red cell size As shown in Figure 62.1 , the reticulocyte count and MCV help in the initial classification of anemia but leave the physician with broad categories of disease, rather than specific diagnoses In many instances, the history and physical examination, when coupled with these laboratory measurements, permit identification of a particular disorder When this is not possible, consultation with a hematologist, additional laboratory studies, and careful examination of the peripheral smear may be required to characterize the disease TABLE 62.4 AGE-RELATED VALUES FOR MEAN CORPUSCULAR VOLUME MCV (fL) Age (yrs) 0.5–2 2–5 5–9 9–12 12–14: Female Male 14–18: Female Male Median Lower limit a 77 79 81 83 70 73 75 76 85 84 77 76 87 86 78 77 a Third percentile fL, femtoliters SUMMARY Pallor can be a sign of severe illness and indicate the need for rapid assessment and emergent stabilization Once this has been initiated, a systematic approach to determine the etiology of pallor should be undertaken Combining elements of the history, physical examination, and laboratory data will assist the clinician in identifying whether the anemia is caused by decreased production, increased destruction, or blood loss As a result, an effective management strategy can be developed Suggested Readings and Key References Burns RA, Woodward GA Transient erythroblastopenia of childhood: a review for the pediatric emergency medicine physician Pediatr Emerg Care 2019;35(3):237–240 Chalco JP, Huicho L, Alamo C, et al Accuracy of clinical pallor in the diagnosis of anaemia in children: a meta-analysis BMC Pediatr 2005;5:46 Grace RF, Glader B Red blood cell enzyme disorders Pediatr Clin North Am 2018;65(3):579–595 Orkin SH, Fisher DE, Look AT, et al., eds Nathan and Oski’s Hematology of Infancy and Childhood 8th ed Philadelphia, PA: WB Saunders; 2015 Subramaniam S, Chao JH Managing acute complications of sickle cell disease in pediatric patients Pediatr Emerg Med Pract 2016;13(11):1–28 ... References Burns RA, Woodward GA Transient erythroblastopenia of childhood: a review for the pediatric emergency medicine physician Pediatr Emerg Care 2019;35(3):237–240 Chalco JP, Huicho L, Alamo C,... WB Saunders; 2015 Subramaniam S, Chao JH Managing acute complications of sickle cell disease in pediatric patients Pediatr Emerg Med Pract 2016;13(11):1–28