Anemia is a serious global public health problem that particularly affects young children in which the red blood cells’ oxygen-carrying capacity is insufficient to meet the body’s physiologic needs. The World Health Organization (WHO) estimates that 42% of children worldwide, less than 5 years of age, are anemic. [1, 2]
Anemia is defined as a reduction in hemoglobin concentration or hematocrit below 2 standard deviations (i.e. below 2.5 percentile) per age, race and sex. [3] It represents a common cause of pediatric and hematological consults in children. It is often asymptomatic or paucisymptomatic; thus, most times it is an occasional laboratory finding. [4]
According to WHO, severity of anemia is defined depending on Hb value (i.e. < 7 g/dL in children < 5 years and < 8 g/dL in children > 5 years). In clinical practice, however, pediatricians define anemia as severe when a marked reduction in hemoglobin value reflects on clinical condition and onset of symptoms.
The timing of development of anemia affects, in turn, the intensity/degree of clinical manifestation. When the decrease of hemoglobin levels is chronic and slow, for example in nutritional deficiencies, patients better tolerate anemia and a wide discrepancy between the laboratory value and the presenting clinical condition may be observed.
Nutritional deficiencies (i.e. iron, folate and vitamins B12) represent one of the most common causes of pediatric anemia. Iron deficiency is the prevalent nutritional deficiency worldwide. [5]
Iron-deficiency anemia (IDA) is the most frequent hematological disease in infancy and childhood. According to World Health Organization statistics, 43% of children worldwide (273 million preschool-age children) are iron deficient; in industrialized countries, 17% of children under 5 years of age suffer from IDA. [1] Factors leading to IDA in children include inadequate dietary iron intake, intestinal malabsorption, and blood losses. [6]
In the context of inadequate iron intake, a focused dietary history is an important screening tool, more accurate than an isolated measurement of hemoglobin level: in a study among 305 healthy African-American children aged one to five years, a brief dietary history revealed a 97% negative predictive value for IDA. [7]
In our patient, a detailed nutritional evaluation including food history, auxological examination and nutritional indices assessment (i.e. total iron binding capacity, prealbumin and vitamin D levels) confirmed a severe picture of faltering growth.
Pediatric cohorts with severe IDA and extremely low hemoglobin levels have been described in literature so far. [8] However, to the best of our knowledge, for the first time we report an occasional and unexpected diagnosis of IDA in which the child reached potentially life-threatening Hb values (Hb 1.9 g/dl) without important signs or symptoms, suggesting another concomitant pathogenetic mechanism.
In our patient, the ethnicity and the clinical picture of anemia raised immediately the suspicion of a hidden hemoglobinopathy.
Sickle cell disease (SCD) is the most important hemoglobinopathy worldwide in terms of frequency (400.000 infants are born each year with SCD) and social impact (SCD il responsible for 5–16% of mortality in children younger than 5 years). [9]
The disease is endemic in several Africans countries (most frequently sub-Saharan Africa) and in some parts of Sicily, Greece, southern Turkey, and India. It has recently been recognized as a global public health problem by the World Health Organization, as the current phenomenon of immigration has contributed to a worldwide diffusion of the disease.
SCD is a chronic hemolytic anemia caused by a mutation in β-globin subunit of hemoglobin. Clinical manifestations of SCD include symptoms related to anemia, repeated infections and periodic episodes of pain (VOC, vaso-occlusive crises). [10] However, both the phenotype of the disease and the onset of symptoms are heterogeneous and may have a pronounced variability among patients. In geographical areas in which a neonatal national screening program for SCD has not been established (i.e. our region in Northern Italy), pediatricians are warranted to have a high suspicion of the disease and screening for HbS should be considered in all patients originating from endemic countries. [11]
However, the observed extreme low levels of hemoglobin would hardly have been explained by SCD alone. Compensatory increase in red blood cell production and adaptation to a lower hemoglobin level (approximately 8 to 10 g/dL) are usually sufficient to prevent major symptoms of anemia in most patients. The concomitant presence of other contributing factor, such as folate or iron deficiency, can determine the breakdown of such unstable balance [12], as observed in our patient.
In conclusion, we report an emblematic example that underline how the slower the anemia is established, the more unbelievable hemoglobin levels are asymptomatically reached.
In our patient, the diagnosis of severe anemia might be considered nearly an occasional laboratory finding as the child unexpectedly reached potentially life-threatening Hb values (Hb 1.9 g/dl) without important signs or symptoms (except for asthenia).
This extreme presentation was the consequence of a very slow decrease of hemoglobin values occurring over years, due to the simultaneous presence of two different well known causes of chronic anemization during childhood: iron deficiency anemia and homozygous sickle cell disease.
When approaching a picture of severe anemia, we suggest pediatricians to take into consideration clinical conditions rather than laboratory values and to take advantage of detailed anamnestic data in order to make the diagnosis.