Anemia

Anaemia is a blood disorder characterised by a reduced capacity of the blood to transport oxygen. This reduction arises from a lower-than-normal number of red blood cells, decreased haemoglobin concentration or functional abnormalities of haemoglobin molecules. The term derives from Greek roots denoting “lack of blood”. Anaemia may develop gradually or abruptly, and its presentation varies considerably depending on severity and underlying cause. It represents the most common haematological condition worldwide and is a major contributor to global morbidity.

Clinical Presentation and Symptomatology

The symptoms of anaemia vary widely and may be minimal when the condition develops slowly. Mild or early-stage anaemia frequently produces non-specific manifestations such as fatigue, weakness, shortness of breath on exertion, headache and diminished exercise tolerance. As the severity increases, additional features may emerge, including dizziness, difficulty concentrating and cold intolerance.
Acute or rapidly developing anaemia can lead to more pronounced symptoms, such as confusion, syncope, excessive thirst and angina, particularly in individuals with pre-existing cardiac disease. Marked pallor of the skin, mucous membranes and nail beds may indicate significant reduction in haemoglobin levels, although pallor alone is an unreliable diagnostic sign.
Specific symptoms may reflect the underlying aetiology. For example:

• Iron deficiency anaemia may cause brittle or spoon-shaped nails (koilonychia), restless legs syndrome and pica, in which individuals crave non-food substances such as ice or soil. A blue tinge to the sclera may occasionally be observed.
• Vitamin B₁₂ deficiency can give rise to neurological symptoms including memory impairment, mood changes, gait disturbance, peripheral neuropathy and, in advanced cases, irreversible nerve damage.
• Haemolytic anaemia may present with jaundice due to accelerated breakdown of red blood cells.
• Thalassaemia may be associated with skeletal abnormalities caused by expanded bone marrow activity.
• Sickle cell disease can lead to painful crises, chronic leg ulcers and organ complications.

In severe anaemia the body compensates for reduced oxygen carriage by increasing cardiac output. This can manifest as tachycardia, palpitations, a bounding pulse, functional murmurs and signs of heart failure. Chronic anaemia in children may lead to behavioural disturbances, delayed neurological development and reduced academic performance.

Aetiology and Pathophysiology

Anaemia can arise from four fundamental mechanisms: impaired red blood cell production, increased red cell destruction (haemolysis), blood loss and, less commonly, dilutional effects such as those seen in hypervolaemia. These mechanisms may coexist in complex clinical scenarios.
Impaired red blood cell production may involve several pathways:

• Stem cell disorders such as Fanconi anaemia and aplastic anaemia reduce the bone marrow’s ability to produce blood cells of all lineages.
• Chronic kidney disease leads to insufficient erythropoietin, the hormone necessary for red cell production.
• Endocrine disorders may impair erythroblast maturation.
• Vitamin B₁₂ and folate deficiencies cause megaloblastic anaemia characterised by large, immature red blood cells due to defective DNA synthesis.
• Iron deficiency remains the most common cause of anaemia globally and results in impaired haem synthesis.
• Globin chain synthesis disorders, including thalassaemias, produce ineffective erythropoiesis.
• Myelophthisic anaemia occurs when normal marrow is replaced by malignant cells, fibrosis or granulomatous tissue.

Increased red blood cell destruction, or haemolytic anaemia, may result from:

• Genetic abnormalities such as sickle cell disease or hereditary spherocytosis.
• Infections including malaria.
• Autoimmune mechanisms, as in autoimmune haemolytic anaemia.

Blood loss remains the most common immediate cause of anaemia. It may be acute (trauma, surgery, gastrointestinal haemorrhage) or chronic (occult gastrointestinal bleeding, heavy menstrual loss). Persistent blood loss often leads to iron depletion and impaired red cell production.

Classification and Diagnostic Evaluation

Anaemia is frequently classified using red cell indices, particularly the mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH):

• Microcytic anaemia (low MCV) usually arises from iron deficiency, thalassaemia or chronic disease.
• Macrocytic anaemia (high MCV) often indicates vitamin B₁₂ or folate deficiency, alcohol misuse or certain medications.
• Normocytic anaemia (normal MCV) may reflect acute blood loss, chronic disease or early-stage nutritional deficiency.

Diagnostic thresholds are generally defined as haemoglobin levels below 13.0–14.0 g/dL in men and below 12.0–13.0 g/dL in women. Once anaemia is detected, further investigation focuses on identifying the underlying cause through full blood counts, reticulocyte counts, iron studies, vitamin B₁₂ and folate levels, markers of haemolysis and, when necessary, bone marrow assessment.

Management Strategies

Treatment of anaemia is determined by the underlying aetiology rather than by the haemoglobin value alone. Approaches include:

• Iron supplementation, particularly beneficial for pregnant women and individuals with proven deficiency. However, empirical supplementation without diagnosis is discouraged.
• Vitamin B₁₂ or folate replacement for megaloblastic anaemias.
• Erythropoiesis-stimulating agents for severe anaemia associated with chronic kidney disease or specific chronic conditions.
• Blood transfusion, generally reserved for individuals with significant symptoms or haemoglobin levels below 6–8 g/dL.
• Treatment of underlying disease, such as managing chronic inflammation, eradicating infectious agents or addressing autoimmune processes.

Global Burden and Public Health Significance

Anaemia affects between one-fifth and one-third of the world’s population, making it a critical global health issue. Iron deficiency alone affects nearly one billion people and remains the leading cause of anaemia worldwide. Mortality due to iron-deficiency anaemia has declined over recent decades, but the condition persists as a major contributor to disability, especially among children, the elderly and women of reproductive age.
The World Health Organization identifies anaemia reduction as a core nutrition target for 2025, aligning with the Sustainable Development Goals. Targeted interventions, including improving dietary quality, addressing micronutrient deficiency, promoting maternal health and controlling parasitic infections, play an essential role in global strategies to reduce anaemia prevalence.