A 22 month old boy presents to your office with a chief complaint of pallor. A visiting relative who has not seen the child for 5 months told his mother that the boy appears pale. The mother brings him in for a checkup even though she notices no change in his coloring (he has always been fair skinned). On review of symptoms you find that he is an active toddler, with no recent fatigue, exercise intolerance, or increase in sleeping. He has had no blood in his diapers and no black or tarry stools. He is a picky eater, taking small amounts of chicken, pork and some vegetables, but loves milk and drinks six to eight bottles of whole milk per day.
Family history reveals a distant aunt who had anemia when she was pregnant but which subsequently resolved. There is no history of splenectomy, gall stones at an early age, or other anemia in the family.
Exam: VS: T 37.5, BP 90/52, P 145, RR 16, Height 85.5 cm (50th %ile), Weight 13.2 kg (75th %ile). General appearance: He is a pale appearing, active toddler, holding a bottle, tearing and eating paper from your exam table. Eyes: No scleral icterus. Pale conjunctiva. Mouth: Dental caries. Chest: Clear. Heart: Mild tachycardia as above, grade II/VI systolic ejection murmur heard best over the upper left sternal border. Abdomen: No hepatosplenomegaly. Rectal: Dark brown, soft stool, negative for occult blood.
CBC: WBC 6,100, Hgb 6.2 g/dl, Hct 19.8%, Plt 589,000, MCV 54 fL, RDW 17%. Reticulocyte count is 1.8%. The lab reports microcytosis, hypochromia, mild anisocytosis and polychromasia. There is no basophilic stippling.
You correctly diagnose iron deficiency anemia, start oral iron and limit his milk intake. You see him in 3 days to assure compliance and his RDW is 27% and his reticulocyte count 17%. When you see him back in two weeks his mother is amazed at his new interest in table foods. His Hgb is now 8.5 g/dl, and his MCV 64 fL. Two months later his hemoglobin has completely normalized, and you continue iron therapy for three more months.
Anemia occurs when the red blood cell mass or hemoglobin content is too low to meet a person's physiologic demands. In children, "normal" levels vary with age, gender, and geographic location (height above sea level). A summary of normal values is listed below (1):
Table 1. Lower limit (3rd %ile) of normal hemoglobin (Hgb column) and lower (3rd %ile) and upper (97th %ile) limit of normal MCV by age and sex (1) (M=males, F=females).
Signs of anemia include pallor of the skin, conjunctiva, and mucous membranes, tachycardia, orthostatic hypotension, heart murmur and edema. Symptoms may include fatigue, headache, dizziness and dyspnea. Other signs and symptoms depend on the cause for anemia, such as jaundice, dark urine, or splenomegaly in hemolytic anemias (2).
When the diagnosis of anemia is suspected based on signs and symptoms, it can quickly be confirmed by laboratory evaluation. The more difficult task is determining the etiology, which can appear daunting due to the myriad of causes of anemia in children. Testing for all these causes at once would be inefficient, time consuming, and expensive. It is, in fact, unnecessary because the differential diagnosis can be narrowed significantly by careful history, thorough examination, and use of various classification schemes.
1) Has there been a sudden onset of pallor, fatigue, or exercise intolerance? Rapid onset of symptoms suggests a more acute anemia, while anemia without symptoms may indicate a more chronic process, allowing the body more time to compensate for the low hemoglobin levels. Note that the presence of symptoms does not necessarily reflect the level of anemia. A child whose Hgb drops from 14 to 10 over one week may be quite symptomatic, while the child in our case presentation was virtually asymptomatic dropping to a Hgb of 6.2 over a period of months. Pallor unrecognized by the patient's day to day caretaker also suggests a gradual process.
2) Any history of blood loss? Obtain a menstrual history. Prolonged, heavy periods are a source for acute blood loss. Over time chronic loss can lead to iron deficiency, especially when superimposed on poor dietary iron intake.
3) Did the child have jaundice in the newborn period or episodes of jaundice in the past? Glucose-6-phosphate dehydrogenase deficiency (G6PD) and hereditary spherocytosis will cause recurrent episodes of jaundice and anemia, especially following illness or stress.
4) Describe the child's diet. When did he start whole milk? How much milk does he drink now? Excessive milk intake with inadequate dietary iron is a common cause of iron deficiency anemia in toddlers. Does he eat anything unusual (paper, dirt) or chew on ice? Pica suggests iron deficiency and can predispose to lead poisoning.
5) Has anyone in the family ever had anemia or low blood counts, or ever been on iron? This may suggest a hereditable cause of anemia, but is not diagnostic. A positive response may simply reflect dietary patterns in siblings. It is quite common for families to recall at least one relative who was anemic at some time, especially during pregnancy. Ask if they are still receiving treatment or if the condition resolved. Also remember that a negative family history does not exclude an inherited anemia.
6) Has anyone in the family ever had their spleen taken out or had gallstones at an early age? Surprisingly, not all patients know the reasons for past procedures, or may have been too young when they occurred. A positive response suggests a family history of a hemolytic anemia (such as hereditary spherocytosis). A negative response does not rule out these causes.
7) What is the child's ethnic origin? Hemoglobinopathies (e.g., sickle cell anemia), thalassemias, and G6PD deficiency are more common in certain ethnic groups.
Compare the child's color to his siblings or both parents. Is he active and playful or fatigued? Tachycardia and heart murmur are common in children with anemia, but look for signs of heart failure including tachypnea, rales, hepatomegaly or edema. Splenomegaly may indicate immune hemolytic anemia or hereditary spherocytosis. Look for any skeletal abnormalities as can be seen with the congenital bone marrow failure syndromes.
Two classification schemes are frequently employed to narrow down the differential diagnosis in anemia. The first uses the MCV to classify the size of the red blood cell as microcytic, normocytic, or macrocytic. Although it can be quite helpful, the system is imperfect. Since MCV values in children vary with age, the age specific MCV values must be used (See Table 1). Even so, certain conditions do not fit neatly into one category. The anemia of inflammation/chronic disease and of lead poisoning can be microcytic or normocytic, and the anemia seen with liver failure can be normocytic or macrocytic.
Microcytic anemias include iron deficiency, thalassemia, chronic inflammation, lead poisoning, and sideroblastic anemia.
Normocytic anemias include acute blood loss, immune hemolytic anemia, hereditary spherocytosis, G6PD deficiency, sickle cell anemia, renal disease, and transient erythroblastopenia of childhood (TEC).
Macrocytic anemias include folate deficiency, B12 deficiency, liver disease, hypothyroidism, neoplasms and bone marrow failure syndromes such as aplastic anemia, Diamond-Blackfan anemia (DBA) and congenital dyserythropoietic anemia (CDEA)
The second classification scheme categorizes anemia by its mechanism. If a patient's hemoglobin is low, it is due to one of three basic reasons: he/she is either not making adequate amounts (decreased production), destroying it (increased destruction), or losing it from somewhere (blood loss). This system is more intuitive and more reliable, but is more difficult to categorize in some cases. A high reticulocyte count indicates that the patient is able to adequately make red cells and is trying to compensate for the anemia, suggesting the cause to be blood loss or destruction. A low reticulocyte count suggests decreased production. Signs of destruction include jaundice, elevated bilirubin, dark urine, splenomegaly, schistocytes and microspherocytes on peripheral smear, and low serum haptoglobin.
Decreased production results from iron, folate, or B-12 deficiency, lead toxicity, thalassemia, aplastic anemia, chronic inflammation, neoplasms, TEC, DBA, renal disease, hypothyroidism, CDEA (congenital dyserythropoietic anemia), and sideroblastic anemia.
Blood loss results from acute hemorrhage, dysfunctional uterine bleeding (heavy and/or prolonged menstrual periods), pulmonary hemosiderosis (pulmonary hemorrhage), Goodpasture's disease, and gastrointestinal blood loss (peptic ulcer disease, other GI conditions).
Increased destruction results from immune hemolytic disease, hereditary spherocytosis, G6PD deficiency, sickle cell disease, thalassemia, DIC (disseminated intravascular coagulation), mechanical heart valves, burns, PNH (paroxysmal nocturnal hemoglobinuria), and hypersplenism.
Iron deficiency is the most common cause of anemia in childhood (2). Prevalence of iron deficiency ranges from 5% to 29% of the population, with higher numbers seen in inner city and socioeconomically deprived populations (3,4). It is most common in toddlers and in the adolescent age groups (periods of rapid growth and higher potential for inadequate dietary iron) (5).
In infants, early introduction (at age 6 or 8 months) of whole cow's milk into the diet is clearly associated with iron deficiency anemia, and patients consuming larger amounts of milk are at higher risk of anemia (3). This is due to three factors: 1) Cow's milk exerts a direct toxic effect on the intestinal mucosa of infants, leading to prolonged microscopic blood loss in the stools. 2) The caloric value of whole cow's milk is high due to fat content, decreasing the appetite and leading to less intake of potential iron-rich foods. 3) The bioavailability of iron in cow's milk is low (6). Accordingly, the American Academy of Pediatrics recommends that cow's milk not be used in the first year of life. Infants should receive breast milk or iron fortified formulas for the first year of life, and iron-fortified cereal should be added at the age of four to six months (6). Infants with appropriate diets and older children and adolescents with iron deficiency anemia must be evaluated for a source of chronic blood loss. Abnormal uterine bleeding and blood loss from the GI tract are common. Blood loss in the urine is rare, and from the lungs (idiopathic pulmonary hemosiderosis) is exceedingly rare. Hemolytic anemias generally do not lead to iron deficiency because the body reuses the freed iron. Iron deficiency has conclusively been linked to behavioral changes (6) and to lower cognitive achievement in school aged children and adolescents (7). Thus it should be recognized early and treated adequately.
Presenting signs and symptoms may be mild because of the gradual onset and the body's ability to compensate for low hemoglobin concentration. Pallor, fatigue, exercise intolerance, headache, or dizziness may be present. Physical exam may reveal pale mucus membranes and skin, especially of the palms, tachycardia with or without heart murmur, and orthostatic hypotension. Laboratory evaluation reveals a low MCV, low hemoglobin and hematocrit, low reticulocyte count, and often an elevated platelet count. The red cell distribution width (RDW), a measure of the difference in size between the smallest and largest RBCs in circulation, may be elevated, denoting a dual population of cells: small (microcytic) iron deficient cells and some normocytic cells with adequate iron. Evaluation of the blood smear reveals microcytosis and hypochromia. Serum iron is low, and total iron binding capacity (TIBC) is elevated with low % saturation. Erythrocyte protoporphyrin is increased. Low serum ferritin is diagnostic of iron deficiency, but normal levels can be misleading because ferritin is an acute phase reactant and can be falsely elevated in inflammation (5). Low-normal ferritin values must be interpreted in light of clues from the history, physical, and other laboratory studies. A bone marrow sample stained for iron shows no iron stores. This test is most definitive, but generally unnecessary and invasive.
Treatment with multivitamins containing iron is inadequate once the child is anemic. Oral ferrous sulfate, available in liquid or pill form, at a dose of 3 mg/kg of elemental iron for mild anemia or 6 mg/kg for severe anemia should be instituted. It should be continued for two to three months after normalization of blood counts to replete the total body iron stores. The liquid can stain the teeth so it should be given in juice rather than dropped directly into the mouth. Avoid giving it with milk as milk interferes with its absorption.
Lead poisoning is less common today with the federally mandated removal of lead from gasoline, canned food sealants, and paint intended for household use in 1977. Since then, there has been a 90% decrease in the number of children defined as "lead intoxicated" (8). Nationwide, 4.4% of children aged one to five meet this criteria with blood levels above 10 mcg/dL (9). The primary source of lead in children's blood today is from lead based paint in older households. Most is ingested as household dust, with only a minor contribution from paint chips (8). Children under 2 years of age are at highest risk due to exploring behavior and the practice of bringing paint dust-coated fingers and toys to the mouth. Not surprisingly, the age and state of disrepair of the home is an important risk factor. Children in an older but well-maintained home have less exposure than those in an old home with cracked and peeling paint (10).
Most lead poisoning is now found through lead screening. The American Academy of Pediatrics recommends that a risk assessment survey be given at health maintenance visits, and if any questions are answered "yes" or "not sure", blood lead levels should be drawn. The survey should be adapted for known lead risks in each community, but should include at least the following three questions (10):
1) Does your child live in or regularly visit a house or childcare facility built before 1950?
2) Does your child live in or regularly visit a house or childcare facility built before 1978 that is being or recently has been renovated or remodeled?
3) Does your child have a sibling or playmate who has or did have lead poisoning?
In communities where more than 27% of housing was built before 1950 or where more than 12% of 1 and 2 year olds have elevated blood lead levels, all children should have lead levels drawn at age 9-12 months and age 2 years (10).
Acute signs and symptoms of lead intoxication are now rarely seen. Vomiting, abdominal pain, and constipation are nonspecific and common in this age group. Because of prevention, screening, and the use of chelating agents as treatment, encephalopathy, seizure, and coma associated with extremely high lead levels are almost unheard of today. Chronic effects of lead poisoning are more ominous, and include possibly permanent behavioral and cognitive deficits, including decrease in IQ points (11,12). Complete blood counts are often normal in children with low to moderately elevated lead levels. Basophilic stippling, seen as fine blue specks in the RBC membrane under light microscopy, can be prominent. Erythrocyte protoporphyrin is elevated (13). Anemia results from lead's inhibition of enzymes required for hemoglobin synthesis (4), but the microcytic anemia of lead poisoning reported in the past is most likely due to concomitant iron deficiency. Iron deficiency leads to pica which increases risk of lead ingestion, and iron deficiency leads to increased absorption and retention of lead from the GI tract.
Treatment depends on the blood lead level (BLL) in mcg/dL (10):
I. BLL <10 requires no action.
II. Levels of 10-20 require education and action to decrease lead exposure, including frequent hand washing, frequent dusting and mopping, and ideally repair or repainting, followed by repeat BLL in 2-3 months.
III. Levels of 20-44 require a detailed history to identify sources of lead exposure, including hobbies (ceramics), vocations (repair of bridges or boats, plumbing, home building/renovating), and contact (car batteries, contaminated soil). Corrective action must be taken to decrease exposure. Consider a home visit or a referral to the local health department for a detailed environmental investigation and referrals for support services.
IV. Levels of 45-69 require all of the above plus initiation of chelation therapy.
V. Levels of 70 or higher require hospital admission for close observation of mental status and immediate IV chelation.
The anemia of inflammation, also called anemia of chronic disease, is the second most common cause of anemia in children after iron deficiency (14). Initially recognized in patients with chronic inflammatory conditions, it has now been shown to occur in the acute setting, accompanying mild self-limiting illnesses such as otitis media or upper respiratory infections (15). The mechanism of anemia is multifactorial, primarily from decreased RBC production (impaired iron utilization and decreased erythropoietin production and response) but also from decreased RBC survival (16). The degree of anemia is usually mild, with hemoglobin concentrations of 10 to 11 g/dl, but can be moderate with hemoglobins of 8 to 9 g/dl. The red blood cells are usually normocytic but can be microcytic (15). Reticulocyte counts are low. Iron studies, if done, show low serum iron, high serum ferritin, and low TIBC. Bone marrow evaluation would show abundant iron stores. Anemia associated with acute inflammation is usually benign and self-limited, resolving 1-2 months after the infection resolves (15). Children with chronic diseases such as rheumatoid arthritis have a more protracted course; even so, the anemia is rarely significant enough to require treatment. High doses of erythropoietin can correct the anemia in those rare cases (14).
Folate and vitamin B12 deficiency are rarely seen in children. They cause a macrocytic anemia which may be accompanied by granulocytopenia and thrombocytopenia. Hypersegmented neutrophils may be seen on peripheral smear of patients with B12 deficiency. The diagnosis is confirmed by low serum concentration of the vitamins (4). B12 deficiency requires a Schilling test to determine the cause of the B12 deficiency (intrinsic factor deficiency, malabsorption due to inflammatory bowel disease, etc.). B12 deficiency is also associated with neuropathic symptoms.
The thalassemias are a group of inherited disorders of hemoglobin synthesis that cause a microcytic anemia. Aberrant hemoglobins have shortened lifespans, so the anemia may be caused by both decreased RBC production and increased destruction. Thalassemia is fully discussed in a separate chapter.
Anemia from bone marrow failure is usually macrocytic. Causes can be congenital (Diamond-Blackfan anemia, congenital dyserythropoietic anemia) or acquired (aplastic anemia, transient erythroblastopenia of childhood). These are discussed in detail in a separate chapter. Replacement of normal bone marrow by malignancy (leukemia or metastatic tumor) can lead to failure of normal red blood cell production, as can restriction of the marrow space by bone in osteopetrosis.
Destruction of red blood cells, or hemolysis, causes release of intracellular contents into the plasma. Consequently, indirect (unconjugated) bilirubin, LDH, and AST (SGOT) may be elevated. The urine may be dark due to excreted hemoglobin or bilirubin. The reticulocyte count is elevated (18). Haptoglobin, a protein that binds free hemoglobin, decreases. A low serum haptoglobin is diagnostic of hemolysis. If the red cells are destroyed in the spleen (extravascular hemolysis) red cell fragments are not seen, and the peripheral smear shows polychromasia and microspherocytes.
Hereditary Spherocytosis (HS) is the most common cause of hemolytic anemia in children. It is inherited in an autosomal dominant pattern in 75% of cases, but family history is not always positive because of variations in severity even among family members. Abnormal membrane proteins cause a loss of portions of the cell membrane, resulting in a rigid red blood cell with a spherical shape. These cells are trapped in the spleen and destroyed, resulting in hemolytic anemia (17). Patients present with jaundice, anemia, and splenomegaly. The reticulocyte count is elevated, and the MCV is normal. An elevated MCHC strongly suggests HS, as it is rarely elevated in any other condition but is high in 50% of those with HS (18). The peripheral smear usually shows spherocytes, but the degree is variable and depends on smear quality. One cannot rule out HS by a lack of spherocytes reported on a peripheral blood smear. The definitive diagnostic test is the incubated osmotic fragility assay, which shows increased hemolysis to osmotic stress.
Patients with HS can have a "hyperhemolytic crisis", which is an acceleration of the rate of hemolysis brought on by infections. They typically present with increased jaundice, pallor, and hemoglobins in the 5-8 g/dl range during or just after a nonspecific viral illness. Blood transfusions may be required. An "aplastic crisis" can occur following infection with human parvovirus B19, the cause of Fifth disease (erythema infectiosum) (18). This virus stops all red cell production in the marrow. The reticulocyte count falls to 0, and in the face of continued RBC destruction without RBC production, the hemoglobin falls precipitously to levels of 3-6 g/dl. Timely blood transfusions can get these patients through this one time complication. HS patients whose siblings contract Fifth disease must be followed closely. Treatment consists of educating the family about the disease and instructing them to come in for examination and blood work at the first signs of pallor, increased jaundice, or fatigue. Splenectomy is curative but because of the risk of post-splenectomy sepsis, especially in those under age five, the surgery is reserved for those with more severe disease. Indications include frequent hyperhemolytic episodes, symptomatic anemia leading to limitation of lifestyle, gallstones, or growth retardation.
G6PD deficiency is the most common of the RBC enzyme defects. The enzyme deficiency causes the red blood cells to be more sensitive to oxidative stress (17). Hemolysis ensues, resulting in jaundice and anemia. It is an X-linked disorder and so it mostly affects males, but females can be variably affected due to random inactivation of one X chromosome or they can be homozygous (mother is a carrier and father has G6PD deficiency). The clinical course is marked by episodic jaundice. Prolonged neonatal jaundice is sometimes seen. Older patients may have a history of jaundice, pallor and anemia that accompanies infections or certain drugs or foods. Different individuals and different ethnic groups (Asian, African, Mediterranean) may have different mutations which result in differing G6PD deficiency severities, so the patients may have different susceptibilities to severe neonatal jaundice, kernicterus and acute hemolytic reactions. Laboratory evaluation reveals a normocytic anemia with variable evidence of hemolysis such as increased bilirubin, decreased haptoglobin, and hemoglobinuria. The blood smear shows fragmented cells, schistocytes, and may show characteristic "bite" cells or "ghost" cells. Special stains for Heinz bodies, denatured hemoglobin, may be positive. A specific G6PD assay is available, and if low, is diagnostic. The test may be falsely elevated to normal levels during or just after acute hemolysis due to a high reticulocyte count, so it should be repeated several weeks after the hemolytic event if the diagnosis appears likely (18).
Patients can make auto-antibodies against red blood cell antigens due to autoimmune syndromes, medications, infections (EBV, mycoplasma, or nonspecific viruses), or unknown reasons. The presentation is variable, but characteristic findings of hemolytic anemia are the norm. Blood smears show microspherocytes but schistocytes are not seen. The direct Coombs test is positive. Treatment with corticosteroids usually results in resolution of the hemolytic anemia (4,17). Intravenous immune globulin (IVIg) and splenectomy have been used with success in cases refractory to corticosteroids.
Maternal antibodies against infant red blood cell groups can cross the placenta and cause varying degrees of hemolysis (alloimmune hemolytic disease of the newborn). The clinical picture ranges from mild hyperbilirubinemia to hydrops and death, but is most often benign and self-limited. Observation alone or treatment with phototherapy is usually adequate. This topic is covered fully in the newborn hematology chapter.
With intravascular hemolysis, as seen in disseminated intravascular coagulation (DIC), hemolytic-uremic syndrome and burns, mechanical injury to red blood cells causes hemolysis within the blood vessel rather than in the spleen. Red blood cell fragments (schistocytes) are therefore commonly seen on peripheral blood smears (4). Treatment involves correction of the underlying condition. Because the defect is extrinsic to the red cell, transfused blood is hemolyzed as quickly as is the patient's, and so transfusion is only a temporizing measure.
Sickle cell anemia is a hemoglobinopathy common in African, Caribbean, Middle Eastern, and Mediterranean peoples. A mutation in the hemoglobin molecule causes red cells to take on a rigid sickled shape, causing obstruction of flow through the microvasculature. Complications due to tissue hypoxia and hemolytic anemia can be profound. Sickle cell anemia is discussed fully in a separate chapter.
1. What two classification schemes can be used to narrow down the differential diagnosis of anemia in children?
2. What laboratory finding suggests that an anemia is due to a decreased production of red blood cells?
3. What elements of the history, physical, and laboratory evaluation suggest increased red cell destruction as the cause of anemia?
4. What is the best test to rule in or rule out iron deficiency? Justify your answer.
5. True/False: A child raised in a lead based paint containing home that is well maintained has a significantly lower chance of lead poisoning than if that home is in disrepair.
6. True/False: Cow's milk exerts a direct toxic effect on the intestinal mucosa of some infants, leading to microscopic blood loss and iron deficiency anemia.
7. True/False: Children with iron deficiency anemia caused by excessive cow's milk intake often have a history of black or tarry stools.
8. True/False: The iron content of cow's milk is zero or very close to zero.
9. The lab reports a patient's hemoglobin as 7 g/dl, and the reticulocyte count as 1%. The published normal value for the reticulocyte count is 0.7% to 2.0%, so the reticulocyte count is within the laboratory's normal range. How would you interpret this reticulocyte count?
. . . . . a. This reticulocyte count is normal, so the patient's bone marrow is making RBCs adequately.
. . . . . b. This reticulocyte count is low. The laboratory's normal values are incorrect.
. . . . . c. This reticulocyte count value is normal for a patient with a normal hemoglobin, but for a severely anemic patient, the reticulocyte count should be high. Thus, in view of this patient's severe anemia, this patient's reticulocyte count is actually low and indicative of a condition in which RBCs are not being produced.
. . . . . d. This reticulocyte count is too high for a low hemoglobin. Thus, this is indicative of a hemolytic etiology.
1. Dallman PR, Siimes MA. Percentile curves for hemoglobin and red cell volume in infancy and childhood. J Pediatr 1979;94:28.
2. Blackwell S, Hendrix PC. Common anemias: what lies beneath. Clin Reviews 2001;11(3):53-62.
3. Booth IW, Aukett MA. Iron deficiency anemia in infancy and early childhood. Arch Dis Child 1997;76(6):549-554.
4. Segel GB. Anemia. Pediatr Rev 1988;10(3):77-88.
5. Wharton BA. Iron deficiency in children: detection and prevention. Br J Haematol 1999;106(2):270-280.
6. American Academy of Pediatrics, Committee on Nutrition. The use of whole cow's milk in infancy. Pediatrics 1992;89(6):1105-1109.
7. Halterman JS, Kaczorowski JM, Aligne A, et al. Iron deficiency and cognitive achievement among school-aged children and adolescents in the United States. Pediatrics 2001;107(6):1381-1386.
8. Markowitz M. Lead poisoning. Pediatr Rev 2000;21(10):327-335.
9. Ellis MR, Kane KY. Lightening the lead load in children. Am Fam Physician 2000;62(3):545-554.
10. American Academy of Pediatrics, Committee on Environmental Health. Screening for elevated blood lead levels. Pediatrics 1998;101(6):1072-1078.
11. Chisolm JJ. The road to primary prevention of lead toxicity in children. Pediatrics 2001;107(3):581-583.
12. Tong S, Baghurst PA, Sawyer MG, et al. Declining blood lead levels and changes in cognitive function during childhood. JAMA 1998;280(22):1915-1919.
13. Piomelli S. Chapter 13 - Lead Poisoning. In: Nathan DG, Orkin SH (eds). Hematology of Infancy and Childhood, fifth edition. 1998, Philadelphia: W.B. Saunders, pp. 480-496.
14. Krantz SB. Pathogenesis and treatment of the anemia of chronic disease. Am J Med Sci 1994;307(5):353-359.
15. Abshire TC. The anemia of inflammation. A common cause of childhood anemia. Pediatr Clin North Am 1996;43(3):623-637.
16. Means RT. Pathogenesis of the anemia of chronic disease: a cytokine-mediated anemia. Stem Cells 1995;13:32-37.
17. Welch JC, Lilleyman JS. Anaemia in children. Br J Hosp Med 1995;53(8):387-390.
18. Sackey K. Hemolytic anemia: part 1. Pediatr Rev 1999;20(5):152-158.
Answers to questions
1. Classification by red blood cell size (microcytic, normocytic, and macrocytic anemias) and classification by mechanism (decreased production, increased destruction, and blood loss).
2. Low reticulocyte count.
3. History: dark urine. Physical exam: jaundice, scleral icterus, splenomegaly. Lab: elevated LDH, AST, indirect bilirubin; decreased serum haptoglobin; positive direct antibody test (DAT, also known as Coombs test), high reticulocyte count.
4. Bone marrow stain for iron has the highest positive predictive value and specificity, but it is too invasive in most instances. Low serum ferritin is diagnostic of iron deficiency, but its wide range of normal values and its fluctuation with acute inflammation may make interpretation difficult. Serum iron coupled with TIBC and % iron saturation are satisfactory, but this test is subject to some laboratory fluctuation as well. Response to a therapeutic trial of iron is also acceptable as proof of iron deficiency. No actual correct answer to this question.
8. False. Cow's milk contains a modest amount of iron, but little of it is bioavailable.