Introduction 

Macrocytosis refers to the prevalence of abnormally large red blood cells (RBC), known as macrocytes, in the blood ¹. This condition is usually detected using a blood test known as complete blood count (CBC), which measures the size and volume of RBC and other parameters.¹ The mean corpuscular volume (MCV) is another blood test used to indicate macrocytosis, by measuring the average size of RBC.¹ Individuals with the condition often have higher-than-normal MCV. 

Even though macrocytosis is more frequently found in adults, it can also be found in young children. This article will focus on the clinical significance, causes, treatment strategies, and ways to manage the condition in children  

Understanding macrocytosis 

To understand macrocytosis, it is essential to grasp the basics of RBC production and function. RBCs are produced in bone marrow, and they are responsible for carrying oxygen from the lungs to the rest of the body and returning carbon dioxide to the lungs for exhalation.²

The size and shape of RBCs can determine their efficient functioning.³ Macrocytosis occurs when RBCs are larger than normal, which can be due to various underlying causes.¹ This condition is not a disease itself, but a sign that something is affecting red blood cell production or maturation.

Causes of macrocytosis in paediatric populations 

Several factors can lead to macrocytosis in children. They can be broadly categorised into nutritional deficiencies, bone marrow disorders, liver disease, and genetic conditions. 

Vitamin B12 and folate nutritional deficiencies

Vitamin B12 and folate (a water-soluble B vitamin) are pivotal for the production and maturation of RBC. Both vitamin B12 and folate are essential for DNA synthesis (the creation of DNA molecules), which is crucial for cell division. Without adequate levels of these vitamins, RBCs are unable to divide properly; eventually leading to the production of large immature cells, or macrocytes.⁴

Vitamin B12 deficiency

Vitamin B12 is essential for DNA synthesis and RBC production. It is mainly obtained from animal products like meat, dairy, and eggs.⁵ A vitamin B12 deficiency can lead to the production of large and immature RBCs.⁴

Children may develop vitamin B12 deficiency because of an inadequate dietary intake, malabsorption disorders (i.e., difficulties absorbing nutrients from food), or inherited conditions affecting vitamin B12 metabolism.

Folate deficiency

Folate, or vitamin B9, is a crucial nutrient for DNA synthesis and cell division. It is found in leafy green vegetables, fruits, nuts, and beans.⁶

Folate deficiency can result from a poor diet, malabsorption syndromes, or an increased requirement of nutrients during periods of rapid growth.⁴

Bone marrow disorders 

Bone marrow disorders can significantly impact RBC production and as a result lead to macrocytosis. When required, healthy bone marrow releases mature blood cells into the bloodstream. Hence, abnormal bone marrow activity can impact RBCs. Some types of bone marrow disorders include:

• Aplastic anaemia: in this condition, bone marrow fails to produce enough blood cells, including RBCs. This can lead to macrocytosis, as the body attempts to compensate for this lack of RBC by producing larger cells⁷ 
• Myelodysplastic syndrome (MDS): this is a rare blood cancer which results in a lack of healthy blood cells. MSD can result in macrocytic RBC⁸

Genetic conditions 

One genetic condition affecting RBC is hereditary spherocytosis, an inherited blood disorder. RBCs in people with this condition are round like a sphere (spherocytes), rather than being shaped like a disk. This increases the fragility of RBCs.⁹

Liver disease 

The liver plays a crucial role in metabolising nutrients and producing the proteins needed for RBC maturation. Liver conditions or diseases can disrupt these processes, in turn affecting RBC maturation.  

Liver diseases, such as hepatitis or cirrhosis, can interfere with these processes, leading to macrocytosis.

• Hepatitis occurs when the liver is inflamed due to a viral infection, impairing its ability to process nutrients and essential proteins¹⁰
• Cirrhosis occurs when abnormal scarring and liver function cause deficiencies in nutrition, and abnormal blood cell production¹¹  

Symptoms and diagnosis 

Macrocytosis often does not present noticeable symptoms, so it is usually discovered incidentally during routine blood tests.¹ However, underlying conditions that lead to macrocytosis can present with various symptoms, including:

• Fatigue and weakness
• Pale skin
• Jaundice (i.e., yellowing of the skin and eyes)
• Shortness of breath
• Developmental delays or growth problems in severe cases

Diagnosing macrocytosis involves several steps

1. Complete Blood Count (CBC): this test measures various blood parameters, including the MCV. An elevated MCV can indicate  macrocytosis¹
2. Peripheral Blood Smear: a microscopic examination of the blood, which can provide information about the shape and appearance of RBCs, aiding the identification of abnormalities¹
3. Nutritional Assessment: blood tests can be used to measure the levels of vitamin B12, folate, and other nutrients, identifying deficiencies¹
4. Bone Marrow Examination: in cases where bone marrow disorders are suspected, a bone marrow biopsy may be performed to examine the bone marrow cells directly¹
5. Liver Function Tests: these tests can assess liver health and identify any underlying liver diseases contributing to macrocytosis¹

Treatment and management of macrocytosis

The treatment of macrocytosis in paediatric populations depends on the underlying cause. Here are some common approaches:

1. Nutritional Supplementation: in cases caused by vitamin B12 or folate deficiencies, vitamin supplements usually prove to be effective. Dietary changes to include more nutrient-rich foods can also help prevent its recurrence¹²
2. Treatment of Underlying Disorders: conditions such as aplastic anaemia, myelodysplastic syndromes, or liver diseases, require specific treatments tailored to the specific condition. This may include medications, blood transfusions, or other therapies¹²
3. Monitoring and Supportive Care: regular monitoring of blood parameters and overall health is crucial for children with macrocytosis. Supportive care, such as managing symptoms and ensuring adequate nutrition, is also important¹²

Prevention

Preventing macrocytosis involves addressing its potential causes and promoting overall health. Some preventive measures include:

1. Balanced Diet: ensuring children receive a nutrient-rich diet, including vitamin B12 and folate, can help prevent nutritional deficiencies. Foods such as meat, dairy products, leafy greens, and fortified cereals, are good sources of these vitamins¹²
2. Regular Health Check-ups: Routine medical check-ups can help detect early signs of macrocytosis or its underlying causes, allowing for a timely intervention¹²
3. Awareness and Education: educating parents and caregivers about the importance of nutrition and recognizing potential symptoms of underlying conditions can contribute to an early diagnosis and better treatment of macrocytosis¹²

Summary 

Macrocytosis in paediatric populations signals an underlying issue with RBC production or maturation. While it can be alarming to discover abnormally large RBC in children, understanding its potential causes and appropriate diagnostic steps can help manage and treat the condition effectively. Nutritional deficiencies, bone marrow disorders, liver diseases, and genetic conditions are some common causes of macrocytosis in children. Addressing these underlying issues through proper medical care, nutritional supplementation, and regular monitoring, can ensure the well-being and healthy development of affected children. By promoting awareness and preventive measures, we can work towards minimising the impact of macrocytosis on paediatric health.