A 14-month-old female came to clinic for her health supervision visit and was found to be healthy and developmentally appropriate. She was drinking 16 ounces of whole milk/day and eating table foods. The family received assistance through federal food programs. Her screening laboratories showed a normal lead test, and a hemoglobin of 11.0 g/dl and hematocrit of 31%. The pediatrician decided to treat her with iron because of the low hematocrit despite the normal hemoglobin because of her social risk factors for iron deficiency anemia. The patient was seen back 6 weeks later by another pediatrician in the practice who obtained additional laboratories including a complete blood count and iron studies which were consistent with iron deficiency anemia. A discussion about when to begin empiric iron therapy and how much iron to treat with occurred with both pediatricians discussing the merits of different options. During the conversation, one asked the other, “Which is more accurate, the hemoglobin or the hematocrit?” Both of them did not know the answer to the specific question.
Iron is an essential nutrient needed for oxygen transport, storage and utilization. There are 3 stages of insufficient iron in the body which form a continuum. Iron deficiency (ID) is absence of measurable iron stores and is the first stage. The second is iron deficient erythropoiesis which is a low iron supply but with no anemia and the third stage is iron deficiency anemia (IDA) where the hemoglobin concentration falls below the normal threshold for age and sex. IDA responds to treatment with iron supplementation with at least 10 g/l in hemoglobin or 3% in hematocrit after 1 or 2 months of supplementation.
ID and IDA are common in every country in the world and are known to cause impaired motor and cognitive development as well as impairing physical growth. Iron deficiency is not the only cause of anemia. Other common causes include vitamin A deficiency, folic acid, Vitamin B12 and riboflavin deficiencies. Infectious diseases such as malaria or inherited conditions that affect red cell production such as alpha- or beta-thalassemia also cause anemia.
According to the World Health Organization, “Iron status can be determined by several well-established tests in addition to measurement of haemoglobin or haematocrit. Unfortunately, however, there is no single standard test to assess iron deficiency without anaemia. The use of multiple tests only partially overcomes the limitation of a single test… and is not an option in resource-poor settings.” The results’ variation in many of the tests used is relatively large including hemoglobin and hematocrit. When arbitrary statistical methods are applied to a population (often 2 standards deviations below the normative value) there will be a number of healthy individuals who will be falsely determined to be ID or have IDA.
For a review of the potential side effects of iron therapy click here.
For a review of iron deficiency anemia and lead poisoning, click here.
For a review of non-correcting causes of anemia, click here.
The World Health Organization has recommendations for assessing iron status based on resource availability in the country (see Table 5 of the first reference below). Hemoglobin or hematocrit in intermediate or adequate resourced countries are tests that are recommended. In resource poor countries, clinical examination is recommended. Both hemoglobin and hematocrit are late indicators of ID and IDA though. The American Academy of Pediatrics recommends universal screening using hemoglobin concentrations and risk factor assessment.
Hemoglobin is well standardized and probably the most widely used measurement for screening and initial treatment indicators for ID or IDA. Hemoglobin concentrations are affected by measurement of red cell mass and plasma volume. The normative value changes based on age, elevation above sea level, ethnicity, gender, pregnancy status, and even some changes that are seasonal. Because the hemoglobin is affected by the plasma volume, capillary sampling methods can affect the results. Capillary samples must have the finger or heel pricked and spontaneously flowing blood used for the sample.
Hematocrit is a measurement of packed cell volume and is a commonly performed test. It is simple to perform and there is widespread availability of the necessary equipment but it has no advantage compared to haemoglobin measurement.
There are other tests can be used to help determine ID and IDA. Serum ferritin is considered the most specific test correlating with relative total body iron stores. Erythrocytes protoprophyrin is the precursor to heme. It is affected by lead poisoning, infections, and other forms of anemia. It is a good test once ferritin levels drop below the cut-off values indicating inadequate tissue supply. ID causes an increase in transferrin and total iron-binding capacity levels and in transferrin saturation but there is great diurnal variation and therefore these are often not used independently. Mean corpuscular volume and mean corpuscular hemoglobin are the two most sensitive red blood cell indices.
Questions for Further Discussion
1. What is the recommended daily allowance of iron for infants and children?
2. What testing can/should be done at follow-up after treatment for suspected IDA?
3. What are the advantages of Hemocue® for determining hemoglobin concentration?
- Disease: Anemia
- Symptom/Presentation: Health Maintenance and Disease Prevention
- Age: Toddler
To Learn More
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World Health Organizaton. Iron deficiency anaemia: assessment, prevention and control. A guide for programme managers Available from the Internet at http://apps.who.int/iris/bitstream/10665/66914/1/WHO_NHD_01.3.pdf
(rev. 2001, cited 10/6/14).
Lynch S. Indicators of the iron status of populations: red blood cell parameters from the World Health Organization. Assessing the iron status of populations. 2nd Edition including Literature Reviews. Available from the Internet at http://www.who.int/nutrition/publications/micronutrients/anaemia_iron_deficiency/9789241596107_annex1.pdf?ua=1 (rev. 2007, cited 10/6/14).
Eden AN, Sandoval C. Iron deficiency in infants and toddlers in the United States. Pediatr Hematol Oncol. 2012 Nov;29(8):704-9.
Thompson J, Biggs BA, Pasricha SR.
Effects of daily iron supplementation in 2- to 5-year-old children: systematic review and meta-analysis. Pediatrics. 2013 Apr;131(4):739-53.
Baker RD, Greer FR. The Committee on Nutrition
Diagnosis and Prevention of Iron Deficiency and Iron-Deficiency Anemia in Infants and Young Children (0-3 Years of Age)
Pediatrics. 2014:126(5);1040 -1050 .
ACGME Competencies Highlighted by Case
1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
2. Essential and accurate information about the patients’ is gathered.
3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
7. All medical and invasive procedures considered essential for the area of practice are competently performed.
8. Health care services aimed at preventing health problems or maintaining health are provided.
9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.
10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.
12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.
13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
14. Knowledge of study designs and statistical methods to appraisal clinical studies and other information on diagnostic and therapeutic effectiveness is applied.
16. Learning of students and other health care professionals is facilitated.
20. Respect, compassion, and integrity; a responsiveness to the needs of patients and society that supercedes self-interest; accountability to patients, society, and the profession; and a commitment to excellence and on-going professional development are demonstrated.
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital