Anemia: Cases & Answers

1. An eight week old is brought to your office with a temperature of 102. A CBC is drawn as part of your work-up for fever. The results show: 10.1> 9.6/29 < 256 MCV 90 RDW 16

Is this patient anemic?

No. The CBC reflects physiologic anemia of infancy. A progressive decline in hemoglobin begins in the first week of life and reaches a nadir at 6-8 weeks of age. The three main factors that contribute to this fall are:

• erythropoiesis temporarily ceases with the onset of respiration at birth
• erythropoietin has a shorter half-life and larger volume of distribution in newborns
• fetal red blood cells have a shortened life-span

CBC results must be interpreted based on norms for age. Tables of norms can be found in a variety of references including the Harriet Lane Handbook. Anemia itself is defined as a hemoglobin less than 2 standard deviation below the mean of healthy children of the same age.

Does this patient require treatment for the low hemoglobin?

Maybe. If the child is premature all of the factors above are exaggerated and there have also likely been frequent blood draws so they are supplemented with iron starting in the NICU.

2. A one year old child last seen at 6 months old comes in with a WIC form. An MA draws a CBC and lead and reminds the parent they need to schedule a visit with the provider.

The lab results show: 8.5 > 10.2/30 < 256 MCV 78.9 MCH 27.8 RDW 13.2 Lead of 2

What type of anemia does this child have based on indices?

Differential Diagnosis of Anemia Adapted from: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson’s Textbook of Pediatrics. 16th ed. Philadelphia: W.B. Saunders Company, 2000: 1462.

Microcytic anemia based on low mean corpuscular volume (MCV)

RDW is a measure of the variation in the size of RBCs. It is elevated in nutritional deficiencies such as iron, B12, and folate deficiencies as well as in some other anemias such as hemolytic anemias.

The Mentzer index ( MCV divided by the RBC count) can help to point to iron deficiency. An index of > 13.5 is suggestive of iron deficiency. An index of <11.5 is suggestive of thalassemia minor. Understanding the concept behind the Mentzer index is more important than memorizing the formula. With iron deficiency the bone marrow cannot produce RBCs normally so both the RBC count and the MCV will be low. With thalassemia minor RBC production is preserved so the RBC count is normal, yet the cells are small and more fragile.

What do you do next?

You need to assure that the child is brought in for a full history and physical.

The initial approach should focus on a detailed history as possible of age, gender, ethnicity, diet, medications, recent illnesses, past/family/social history. Your physical exam should include vital signs, general appearance, skin and mucous membranes, lymph nodes, cardiovascular exam, abdominal exam to evaluate for masses or hepatosplenomegaly. If the child has no history of illness or confounding findings on physical exam a repeat CBC with differential and reticulocyte count should be done. The rest of your work-up will be based on history and physical exam.

3. A grandparent brings in her 3 year old grandchild of whom she has recently gained custody. She brings in a vaccine card which shows the child had a Hg of 8 for a WIC visit 2 days ago.

Results of your screening CBC and lead show:

• 8.5 > 8.2/26 < 256
• MCV 69.1
• Lead 3
• RDW 20
• Reticulocyte count 1
• Mentzer index 15.3

You obtain a dietary history that explains your findings. What have you heard? What changes do you suggest?

During the first year of life, infants require the absorption of 0.8 mg/day of iron (0.6 for growth and 0.2 to replace ongoing losses). Human milk and cow’s milk contain 0.5 mg/L but 50% of iron from human milk is absorbed, while only 10% of iron from cow’s milk is absorbed. Although all infants who receive formula need to be on formula with iron, less than 5% of iron from iron-fortified formulas, which contain 10-30 mg/L is absorbed. The AAP recommended supplementation of the diet with iron-rich foods such as fortified infant cereals after 6 months of age.

Toddlers often have diets that do not contain enough iron-rich foods. Dietary risk factors include early introduction of cow’s milk (before 1 year of age) and consumption of greater than 24 oz/day of cow’s milk. Cow’s milk is low in iron, interferes with iron absorption, and may cause occult gastrointestinal bleeding. Occult bleeding caused by consumption of large amounts of cow’s milk, or Lahey-Heiner syndrome, is an exudative enteropathy caused by a heat-labile toxin in cow’s milk. There is an inverse relationship between age and incidence of Lahey-Heiner syndrome.

Increased juice intake may also decrease the child’s appetite for iron rich foods. Iron rich foods include meat, fish, bread, noodles, cereals and leafy green vegetables.

Iron absorption takes place in the duodenum and upper jejunum. Its absorption is enhanced by an acidic environment and is inhibited by phytate, tannins, and the fiber of cereal grains.

What do you advise next?

• Decrease in milk/juice intake with increased intake of iron-rich foods

• Start iron therapy for iron deficiency anemia with ferrous sulfate. Calculate the dose based on 2 mg/kg/day. One can only absorb about one mg/kg/day of iron due to limited transport protein availability. Taking iron with an ascorbic acid containing beverage such as a small amount of orange juice may enhance absorption.

• Repeat the CBC with retic count in one week if concerned about diagnosis/response.

A rise in reticulocyte count should occur within 3 days. Hemoglobin should increase at least one gram after 4 weeks of treatment. Usually it is acceptable to repeat studies in one month if anemia is mild and the child shows no signs/symptoms of anemia.

• Iron deficiency progresses from storage iron deficiency to iron-limited erythropoiesis to iron deficiency anemia. IDA is the last step and the first to recover.

You must treat to replete stores – usually stated to require 3 months of iron therapy.

• Interestingly the pagophagia (pica for ice) which is considered specific for iron deficiency responds rapidly to treatment with iron even if the child is not yet anemic or before you see an increase in hemoglobin.

Why do we choose to treat?

We are not only treating to prevent/reverse symptoms of fatigue, exercise intolerance, irritability, anorexia and potential tachycardia and cardiac dilatation, but also because iron deficiency early in life can have measurable effects on cognitive achievement.
Remember that some of the tests mentioned might be affected by an acute infection. Ferritin, an acute phase reactant, may increase ignificantly with infection. A high serum ferritin in the setting of infection may falsely reassure you that the patient has normal iron stores. The serum iron concentration and TIBC may be decreased during active infection, making these levels difficult to interpret.

What if the hemoglobin does not improve with iron therapy?

In children with microcytic anemia who do not respond to iron therapy, you must consider hemoglobinopathies or lead poisoning.

Understanding iron and heme physiology explains the significance of the following lab studies. In brief, iron is absorbed in the proximal small intestine bound to transferrin, which mediates its uptake into RBC precursors through the transferrin receptor. The iron is released and incorporated into heme. Iron outside of Hgb-producing cells is stored in ferritin. 60-70% of total iron is found in Hgb. A small amount is found in heme and nonheme enzymes and myoglobin. The remainder is stored in ferritin, located primarily in the liver, bone marrow, spleen, and muscle.

Laboratory studies to consider:

• CBC - repeat to evaluate current status, and to rule out laboratory error.
• Reticulocyte count - to evaluate RBC production in response to anemia.
• Serum ferritin – storage form of iron, earliest marker of iron deficiency, and highly specific (but not sensitive because it is an acute phase reactant).
• Serum iron concentration – decreases as stores are depleted, but may be affected by meals, infection, inflammation, and diurnal variation
• Total iron binding capacity (TIBC) – indirectly measures transferrin, a specific carrier protein for iron. TIBC may also be decreased with malnutrition, inflammation, and chronic infection.
o You can then calculate the transferrin saturation which equals the serum iron over the TIBC and is always low (less than 16%) in iron deficiency anemia.
• Zinc protoporphyrin (ZPP) – formed when zinc is incorporated into protoporphyrin instead of iron in final step of heme biosynthesis. Detects iron deficiency before onset of anemia, but may also be elevated with lead poisoning and chronic disease.
• Lead level - The CDC guidelines recommend assessing risk for lead poisoning at 9-12 months of age and 24 months of age. Universal screening is suggested in some communities. Targeted screening is recommended for communities where <12% of children have blood lead levels >10 micrograms/dl or where <27% of houses were built before 1950.
• Hemoglobin electrophoresis – to determine if hemoglobinopathy is cause of microcytic anemia. Asymptomatic microcytic anemia that is not responsive to iron therapy may be secondary to beta-thalassemia trait. Note that alpha-thalassemia will not be evident on a hemoglobin electrophoresis after the newborn period

4. A teenage girl comes in for a routine annual visit. She has regular menses monthly lasting 7 days. She reports she eats fruits, vegetables and meats and drinks juice, water and soda.

You order a CBC with these results: 6.5 > 10.6/ 34 < 256 MCV 69.1 RDW 16

What advice do you give her?

Iron deficiency is still common in children without notable dietary extremes. The national Health and Nutrition Examination Survey (1988-1994) found that 13% of one year olds, 5% of 2 year olds, 9% of adolescent females (12-15 years old) and 11% of women of childbearing age (16-49 years old) were iron deficient. Infants, toddlers, adolescents and pregnant women are especially at risk secondary to their relative rapid growth and increased demand for iron. Menstruating females need additional iron to replace losses from menstruation. Dietary counseling regarding iron-fortified cereals and iron-rich foods should be discussed at the 6-18 month visits and in adolescence.

The AAP recommends screening for anemia between 9 and 12 months of age, once between the ages of 11 and 21 for all adolescents and annually for menstruating females.