General Clinical Features of Anaemia

• Breathlessness, fatigue, headaches, palpitations, faintness
• Exacerbation of cardiorespiratory problems (angina, intermittent claudication)

• Pallor, tachycardia, systolic flow murmur, cardiac failure

1. Iron Deficiency Anaemia

Symptoms & Signs

• Brittle nails
• Koilonychia (spoon-shaped nails)
• Atrophy of the papillae of the tongue
• Angular stomatitis
• Brittle hair
• Plummer–Vinson (Paterson–Brown–Kelly) syndrome: dysphagia and glossitis
• Plus the general anaemia symptoms above

Complications

• Gastrointestinal blood loss (may reveal underlying colorectal malignancy, peptic ulceration, inflammatory bowel disease)
• If caused by malabsorption (e.g., coeliac disease), the underlying condition progresses untreated
• In pregnancy: placental failure, intrauterine growth retardation, increased maternal morbidity

2. Megaloblastic Anaemia

Symptoms (Box 25.31)

• Malaise (90%)
• Breathlessness (50%)
• Paraesthesiae (80%)
• Sore mouth (20%)
• Weight loss
• Impotence
• Poor memory
• Depression
• Personality change
• Hallucinations
• Visual disturbance

Signs (Box 25.31)

• Smooth tongue
• Angular cheilosis
• Vitiligo
• Skin pigmentation
• Heart failure
• Pyrexia
• In pernicious anaemia: lemon-yellow colour (pallor + mild jaundice)

Neurological Features (B₁₂ deficiency only — Box 25.33)

• Peripheral nerves: glove and stocking paraesthesiae, loss of ankle reflexes
• Spinal cord: subacute combined degeneration of the cord
  • Posterior columns — diminished vibration sensation and proprioception
  • Corticospinal tracts — upper motor neuron signs
• Cerebrum: dementia, optic atrophy, autonomic neuropathy
• Ataxia of gait

Complications

• Pancytopenia (if severe)
• Neurological damage that may be irreversible if untreated
• Hypokalaemia on starting treatment
• Rapid depletion of iron stores on treatment
• Worsening of neurological features if folic acid given alone in B₁₂ deficiency
• Cardiac failure if transfusion given (cardiovascular system is adapted to chronic anaemia; volume load may cause decompensation)
• In pernicious anaemia: increased risk of gastric carcinoma (1%–3%)

3. Thalassaemia

Beta-Thalassaemia Major (Transfusion-Dependent)

• Failure to thrive and recurrent bacterial infections (from first year of life)
• Severe anaemia from 3–6 months of age
• Extramedullary haemopoiesis → hepatosplenomegaly and bone expansion
• Classical thalassaemic facies (bossing of skull)
• Skull X-ray: "hair-on-end" appearance of bony trabeculation

• Iron overload (from repeated transfusions — transfusion haemosiderosis):
  • Damage to endocrine glands, liver, pancreas, myocardium
  • Cardiomyopathy and cardiac tachyarrhythmias (leading causes of morbidity and mortality)
• Splenomegaly causing mechanical problems and excessive transfusion needs
• Bone deformities (diagnostic feature listed in Box 38.1 of the PDF)
• Erythropoietic failure

Beta-Thalassaemia Minor (Carriers/Heterozygotes)

• Mild anaemia
• Microcytic hypochromic erythrocytes (not iron-deficient)
• Some target cells
• Punctate basophilia
• Raised haemoglobin A₂ fraction
• Little or no clinical disability

Non-Transfusion-Dependent Thalassaemia (NTDT / "Thalassaemia Intermedia")

• Symptomatic moderate anaemia (Hb 70–100 g/L)
• Splenomegaly
• Bone deformities
• Recurrent leg ulcers
• Gallstones
• Recurrent infections
• Iron overload despite no regular transfusions (due to excessive iron absorption from dyserythropoiesis)

Alpha-Thalassaemia

• 1 gene deleted: no clinical effect
• 2 genes deleted: mild hypochromic anaemia
• 3 genes deleted (HbH disease): moderate anaemia, splenomegaly
• 4 genes deleted: hydrops fetalis (stillbirth) — incompatible with life

4. Haemolytic Anaemia

General Features of Haemolysis

• Anaemia
• Jaundice (raised unconjugated bilirubin — mild, from red cell breakdown)
• Splenomegaly (in chronic haemolysis)
• In hereditary spherocytosis: may present with gallstones or leg ulcers

• ↓ Haemoglobin
• ↑ Unconjugated bilirubin
• ↑ Lactate dehydrogenase (LDH)
• ↑ Reticulocytes
• ↑ Urinary urobilinogen

• ↓ Haptoglobin
• ↑ Methaemalbuminaemia
• Positive urinary haemosiderin
• Haemoglobinuria (red-brown urine)

Complications

• Aplastic crisis: parvovirus (erythrovirus) infection invades red cell precursors → severe anaemia, low reticulocyte count
• Megaloblastic crisis: folate deficiency from compensatory hyperplasia
• Haemolytic crisis: increased severity of haemolysis, usually with infection (hereditary spherocytosis)
• Pigment gallstones (up to 50% of patients with hereditary spherocytosis)
• Folate deficiency (from compensatory erythroid hyperplasia)
• Leucoerythroblastic blood film (if marked)
• Chronic organ damage from iron deposition (intravascular haemolysis)
• Thrombosis in paroxysmal nocturnal haemoglobinuria (venous and arterial)

5. Aplastic Anaemia

Clinical Features

• Anaemia (fatigue, breathlessness, pallor)
• Bleeding — often the predominant initial presentation:
  • Bruising on minimal trauma
  • Blood blisters in the mouth
  • Ecchymoses
  • Bleeding gums
  • Epistaxis
• Infection (mouth infections common)
• Lymphadenopathy and hepatosplenomegaly are rare

Investigations showing severity:

• Pancytopenia
• Virtual absence of reticulocytes
• Hypocellular or aplastic bone marrow with increased fat spaces

Complications

• Death from haemorrhage or infection (if untreated)
• Progressive, increasingly severe pancytopenia
• Evolution to myelodysplasia, paroxysmal nocturnal haemoglobinuria, or acute myeloid leukaemia (due to emergence of an abnormal clone)
• Overwhelming sepsis (particularly from encapsulated organisms after splenectomy; risk of infection is the main concern)
• Serum sickness from antithymocyte globulin treatment
• Graft rejection, graft-versus-host disease, and viral infections after stem cell transplantation

• Neutrophil count < 0.5 × 10⁹/L
• Platelet count < 20 × 10⁹/L
• Reticulocyte count < 40 × 10⁹/L

6. Sickle Cell Anaemia

Clinical Features

Acute Crises:

• Plugging of small vessels in the bone → acute severe bone pain
• In children: hands and feet (dactylitis)
• In adults: femora, humeri, ribs, pelvis, vertebrae
• Systemic response: tachycardia and fever

• Single most devastating consequence
• Occurs in 10%–15% of children with sickle cell disease
• Silent stroke also occurs

• Follows vaso-occlusive crisis
• Bone marrow infarction → fat emboli to lungs → further sickling and infarction → ventilatory failure

• Thrombosis of venous outflow from an organ → loss of function and acute painful enlargement
• In children: spleen (most common) → massive splenic enlargement → severe anaemia, circulatory collapse, death
• In adults: liver sequestration with severe pain; priapism may occur

• Parvovirus B19 infection → severe but self-limiting red cell aplasia
• Profound anaemia, may cause heart failure
• Reticulocyte count is low (unlike other crises)

• Painful crises, placental failure, thrombosis
• Pre-eclampsia, intrauterine growth retardation

Chronic/Long-Term Complications (Fig. 25.24):

Prognosis

• In Africa, approximately 15% die by age 20 and 50% by age 40 even with standard medical care.