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Macrocytic Anaemia

Macrocytic anaemia is a condition characterised by the presence of abnormally large red blood cells (erythrocytes) in the blood, which leads to a lower concentration of haemoglobin.

The term "macrocytic" derives from Greek, meaning "large cell." The normal erythrocyte volume in humans ranges from 80 to 100 femtoliters. When the red blood cells exceed this size, the condition is termed macrocytosis. This type of anaemia is not a single disease but rather a class name for various pathologies that produce similar red blood cell abnormalities.

Signs and Symptoms

Macrocytic anaemia presents with various signs and symptoms, including:

  • Fatigue
  • Weakness
  • Pallor
  • Shortness of breath
  • Palpitations

Patients may also exhibit neurological symptoms if the anaemia is due to Vitamin B12 deficiency.

Causes

Megaloblastic Anemias

Megaloblastic anemias are a type of macrocytic anaemia characterised by the presence of enlarged, oval-shaped red blood cells (macroovalocytes) and hypersegmented neutrophils. This type of anaemia is caused by impaired DNA synthesis and repair, often due to thymidine production deficiency. Common causes include Vitamin B12 and folic acid deficiencies. Other causes include medications that interfere with DNA synthesis or the absorption of Vitamin B12 or folate, such as methotrexate, sulfasalazine, metformin, and anticonvulsant medications.

Non-Megaloblastic Anemias

Red Cell Membrane Disorders

Non-megaloblastic macrocytic anemias can be caused by disorders that increase red cell membrane surface area, such as liver and spleen pathologies, producing codocytes or "target cells."

Alcohol

Chronic alcoholism can lead to round macrocytes due to the toxic effects of alcohol on the bone marrow, making it one of the most common causes of macrocytosis and non-megaloblastic macrocytic anaemia.

Rapid Red Cell Turnover and Reticulocytosis

Conditions associated with rapid blood production, such as chronic obstructive pulmonary disease (COPD) or rapid haemolysis, can also lead to mild macrocytosis. Newly produced red cells (reticulocytes) are larger than average, contributing to this condition.

Diagnosis

Several tests are used to diagnose macrocytic anaemia and determine its underlying cause. A peripheral blood smear is often the first step to distinguish between megaloblastic and non-megaloblastic macrocytic anaemias. For non-megaloblastic anaemias, a reticulocyte count can be helpful. A low reticulocyte count indicates poor bone marrow response, suggesting liver disease, hypothyroidism, alcohol toxicity, or myelodysplasia. A high reticulocyte count may indicate haemolysis or bleeding.

For megaloblastic anaemias, tests include serum levels of Vitamin B12, methylmalonic acid, and homocysteine. If these tests do not indicate Vitamin B12 or folic acid deficiency, other causes such as copper deficiency, medications, and inborn errors of metabolism may be considered.

Treatment

Treatment of macrocytic anaemia depends on the underlying cause. For megaloblastic anaemias due to Vitamin B12 or folic acid deficiencies, supplementation of these vitamins is the primary treatment. For non-megaloblastic anaemias, addressing the underlying condition, such as reducing alcohol consumption or managing liver disease, is essential. In cases where medication is the cause, adjusting or changing the medication may be necessary.

Epidemiology

The causes of macrocytic anemias vary geographically. In North America, folic acid deficiency has become rare due to folic acid fortification, making Vitamin B12 deficiency the more common cause of megaloblastic anaemia. In contrast, in regions without such fortification practices, such as most European countries, folic acid deficiency remains a common cause of macrocytic anaemia.


Self-assessment MCQs (single best answer)

What is the characteristic feature of macrocytic anaemia?



Which of the following ranges indicates normal erythrocyte volume in humans?



Which vitamin deficiency is commonly associated with neurological symptoms in macrocytic anaemia?



Megaloblastic anaemias are characterised by:



Which of the following is a common cause of non-megaloblastic macrocytic anaemia?



A high reticulocyte count in macrocytic anaemia may indicate:



Which test is often the first step to distinguish between megaloblastic and non-megaloblastic macrocytic anaemias?



What is the primary treatment for megaloblastic anaemias due to Vitamin B12 deficiency?



Which condition is a common cause of macrocytic anaemia in regions with folic acid fortification practices?



Which medication can interfere with the absorption of Vitamin B12 or folate and cause macrocytic anaemia?



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