Aplastic Anaemia

Question 1

Define Aplastic Anaemia

Answer 1

Aplastic anaemia (AA) is defined by pancytopenia with hypocellular marrow and no abnormal cells (blasts, fibrosis, dysplasia) - in contrast to aplastic crisis characterized by anaemia only

Question 2

Explain the aetiology/risk factors for Aplastic Anaemia

Answer 2

ACQUIRED

• Idiopathic (MOST COMMON): autoimmune attack of haematopoietic stem cells
• Toxic injury to haematopoietic stem cells
  
  • Drugs (NSAIDs, sulphonamides, chloramphenicol)
  • Chemicals (e.g. benzene)
  • Ionising Radiation
• Viral (Hep B, Parvovirus B19)

INHERITED

• Paroxysmal Nocturnal Haemoglobinuria
  
  • Gene mutation in a myeloid stem cell in BM
  • All progeny cells (RBC, Platelets, Neutrophils) lack protective membrane protein (glycosylphosphatidylinositol (GPI)-anchored complement inhibitors) so are susceptible to INTRAVASCULAR complement-mediated RBC lysis
    Leads to morning haemoglobinuria, thromboses & infection
• FHx of Fanconi’s Anaemia (MOST COMMON): an autosomal recessive defect in DNA repair that leads to BM failure -> has cafe-au-lait spots

Question 3

Summarise the epidemiology of aplastic anaemia

Answer 3

• Patients can be affected at any age
• Annual incidence: 2-4/1,000,000

Question 4

Recognise the presenting symptoms of aplastic anaemia

Answer 4

NOTE: There are no pathognomonic features. Can be both slow-onset (months) or rapid-onset (days)

Anaemia Symptoms:

• Tiredness
• Exertional Dyspnoea
• Tachycardia

Thrombocytopaenia Symptoms:

• Easy bruising
• Bleeding gums
• Epistaxis

Leukopenia Symptoms:

• Increased frequency and severity of infections

Question 5

Recognise the signs of aplastic anaemia on physical examination

Answer 5

Anaemia Signs:

• Pallor

Thrombocytopaenia Signs:

• Petechiae
• Bruises/ecchymosis

Leukopaenia Signs:

• Multiple bacterial and fungal infections
• No hepatomegaly, splenomegaly or lymphadenopathy

Question 6

Identify appropriate investigations for aplastic anaemia and interpret the results

Answer 6

Bloods

FBC

• Low Hb
• Normal MCV - normocytic normochromic anaemia
• Low platelets
• Low WCC
• Low or absent reticulocytes (evidence of hyperproduction)
• Increased EPO

Blood Film

• Exclude leukaemia (check for abnormal circulating white blood cells)

Bone marrow biopsy

• Shows hypocellularity, normal morphology and absence of malignancy, fibrosis or dysplasia (a.k.a. dry tap/empty marrow)