Microcytic Anaemia

Anaemia caused by deficient haemoglobin synthesis (cytoplasmic defect)

Aetiology

• Haem deficiency
• Lack of iron for erythropoiesis
• Iron deficiency - most common cause of microcytic anaemia
• Anaemia of chronic disease - IL-6 is released due to chronic diseases and increases production of hepcidin, which subsequently down regulates ferroportin expression, reducing iron absorption and precipitating anaemia of chronic disease
• Problems with porphyrin synthesis
• Sideroblastic anaemia: excess iron buildup in mitochondria due to failure to incorportae iron into haem, can be hereditary (congenital sidoblastic anaemias) or aquired e.g. MDS, lead poisoning, alcohol excess

• Globin deficiency
• Thalassaemia (trait, intermedia, major)

Causes of iron deficiency

• Insufficient intake to meed physiological need
• More likely in women and children due to greater requirements
• Dietary factors

• Losing too much - bleeding
• Causes of chronic blood loss: menorrhagia, gastrointestinal (tumours, ulcers, NSAIDs, parasitic infection), haematuria

• Not absorbing enough - malabsorption e.g. coeliac disease (less common)

Pathophysiology

• In microcytic anaemia, one of the building blocks needed to synthesize Hb in the cytoplasm is lacking

• However the nuclear machinery is intact, so the cells can keep dividing

• This results in microcytic (small) cells, and as they contain little Hb they are hypochromic (lacking in colour)

Iron metabolic pathway

• ‘Closed’ system - only able to absorb a small amount of iron, with a tiny amount in circulation moving to/from storage

• Iron turnover in plasma pool is frast

• Circulating iron is bound to transferrin, a protein which transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (especially erythroid marrow)

• % saturation of transferrin with iron measures iron supply
• Reduced in iron deficiency, but also in anaemia of chronic disease
• Increased in genetic haemachromatosis

• Iron is stored in ferritin mainly in the liver
• Ferritin is a large spherical intracellular protein which stores up to 4000 ferric ions
• Serum ferritin is an easily measured indirect measure of storage iron (reflects intracellular ferritin sythesis in response to iron status of the host)
• Low ferritin means iron deficiency

Anaemia of chronic disease

1. Inflammatory cytokines result in increased transcription of ferritin mRNA

2. Ferritin synthesis is increased

3. Inflammatory cytokines also result in increased plasma hepcidin - blocks ferroportin-mediated release of iron

4. Results in impaired iron supply to marrow erythroblasts and eventually hypochromic red cells

Sequential consequences of negative iron balance

1. Exhaustion of iron stores (ferritin falls)

2. Iron deficient erythropoiesis (MCV falls)

3. Microcytic anaemia develops

4. Epithelial changes (effects elsewhere) - skin, koilonychia, angular chelitis

Clinical presentation

• Anaemia - breathlessness, fatigue, headaches, palpitations, faintness, pallor

• Clinical features of iron deficiency are generally only seen in cases of very longstanding deficiency:
• Brittle nails
• Spoon-shaped nails (koilonychia)
• Atrophy of the papillae of the tongue
• Angular stomatitis
• Brittle hair
• Dysphagia and glottitis

Investigations

• Blood count and film
• Red cells are microcytic (MCV <80 fL) and hypochromic (mean corpuscular haemoglobin (MCH) <27 pg)
• There is poikilocytosis (variation in shape) and anisocytosis (variation in size)
• Teardrop Cell
• Pencil Cell / Cigar Cell

• Iron Profile

• Others indicated by history and examination e.g. upper and/or lower GI investigations in all males and postmenopausal females

Management

Iron deficiency anaemia

• Improve iron intake
• Review diet
• Increase iron intake
• Avoid tea, coffee
• Improve gastric acidity
• Vitamin C may benefit

• Review other medication e.g. anticoagulants, PPIs

• Oral Iron (First-Line)
Indications
• Mild–moderate IDA
• Intact GI absorption
• Hemodynamically stable
Preparations (elemental iron content)

Preparation	Elemental Iron
Ferrous sulfate 325 mg	~65 mg
Ferrous fumarate 300 mg	~107 mg
Ferrous gluconate 300 mg	~39 mg

Dose
• 150–200 mg elemental iron/day
• Given once daily or alternate-day dosing (better absorption, fewer GI effects)
Administration Tips
• Take on empty stomach
• Vitamin C enhances absorption
• Avoid concurrent tea, coffee, calcium, PPIs
Duration
• Continue 3 months after Hb normalization to replenish stores
Expected Response
• Reticulocytosis: 7–10 days
• Hb rise: ~1–2 g/dL every 2–3 weeks

• Parenteral (IV) Iron
Indications
• Oral iron intolerance or noncompliance
• Malabsorption (e.g., celiac disease, post-gastrectomy)
• Severe anemia with need for rapid repletion
• Ongoing blood loss
• Chronic kidney disease (especially on ESA)
Common Preparations
• Iron sucrose
• Ferric carboxymaltose
• Ferric derisomaltose
Advantages
• Faster repletion
• Bypasses GI tract
Risks
• Hypersensitivity (rare with newer agents)
• Hypophosphatemia (carboxymaltose)

• Blood Transfusion (Supportive, Not Definitive)
Indications
• Hb <7 g/dL (or <8 g/dL with cardiovascular disease)
• Hemodynamic instability
• Symptomatic severe anemia (angina, syncope, heart failure)
⚠️ Always follow with iron therapy—transfusion does not correct iron deficit.

Anaemia of chronic disease

• Treat underlying cause