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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Pancytopenia (low Hb, low WCC, low platelets) with hypocellular/fatty bone marrow on biopsy
- Most cases are idiopathic (thought autoimmune — T-cell mediated destruction of haematopoietic stem cells)
- Drug causes: chloramphenicol, carbamazepine, NSAIDs, gold, penicillamine, sulphonamides, methotrexate
- Other causes: parvovirus B19, hepatitis (seronegative), radiation, Fanconi anaemia (inherited — children)
- Treatment: young patients with matched sibling → allogeneic stem cell transplant. Older patients → immunosuppression (ATG + ciclosporin)
Overview
Aplastic anaemia is a syndrome of bone marrow failure characterised by peripheral pancytopenia and a hypocellular bone marrow. The underlying pathology in most acquired cases is autoimmune — activated cytotoxic T-lymphocytes attack haematopoietic stem cells, leading to their destruction. This distinguishes it from myelodysplastic syndrome (which is a clonal stem cell disorder with typically hypercellular or normocellular marrow). Severity is classified by the Camitta criteria based on neutrophil count, platelet count, and reticulocyte count.
Epidemiology
Aplastic anaemia is rare, with an annual incidence of approximately 2 per million in Europe. It has a bimodal age distribution with peaks in young adults (15-25 years) and the elderly (>60 years). It is 2-3 times more common in East Asia. Males and females are equally affected. Drug-induced aplastic anaemia is an important and potentially preventable cause.
Clinical Features
Symptoms
Fatigue, pallor, breathlessness (anaemia)
Recurrent or severe infections (neutropenia) — especially mouth ulcers, sore throat, fever
Easy bruising and bleeding (thrombocytopenia) — petechiae, epistaxis, menorrhagia, gum bleeding
Insidious onset over weeks to months (though can be acute)
Signs
Pallor
Petechiae, purpura, bruising
Mouth ulcers, signs of infection
NO lymphadenopathy or hepatosplenomegaly (unlike leukaemia) — important negative finding
Investigations
First-line
FBCPancytopenia: low Hb, low WCC (specifically neutrophils), low platelets. Reticulocyte count low/absent
Blood filmAbsence of abnormal cells (no blasts — distinguishes from leukaemia). Normochromic normocytic or macrocytic red cells
Reticulocyte countLow — critical distinguishing feature (marrow is not producing cells, unlike haemolysis where reticulocytes are high)
Second-line
Bone marrow biopsy (trephine)ESSENTIAL for diagnosis — shows HYPOCELLULAR marrow with fat replacement. Trephine biopsy is required (aspirate alone is insufficient)
Viral serologyHepatitis A/B/C, EBV, CMV, parvovirus B19, HIV
Autoimmune screenANA, dsDNA — exclude SLE-associated pancytopenia
Specialist
Flow cytometry for PNH cloneGPI-anchored protein analysis — PNH clone present in ~50% of aplastic anaemia patients (overlap syndrome)
CytogeneticsExclude myelodysplastic syndrome (which may have chromosomal abnormalities)
Chromosomal fragility testingDEB/MMC test if <40 years — to exclude Fanconi anaemia (autosomal recessive, increased chromosomal breakage)
1
Supportive care
- Red cell transfusions for symptomatic anaemia (use irradiated and CMV-negative products if transplant candidate)
- Platelet transfusions if bleeding or platelets <10 × 10⁹/L
- Prompt broad-spectrum antibiotics for any fever (neutropenic sepsis protocol)
- Avoid unnecessary transfusions pre-transplant (reduces alloimmunisation risk)
2
Definitive treatment — young patients (<40-50) with matched sibling donor
- Allogeneic haematopoietic stem cell transplant — treatment of choice
- Best outcomes in younger patients with HLA-matched sibling
- 5-year survival >80% in children, >70% in young adults
3
Definitive treatment — older patients or no matched donor
- Immunosuppressive therapy (IST): horse anti-thymocyte globulin (ATG) + ciclosporin + eltrombopag
- Response rate approximately 60-70% — response may take 3-6 months
- Eltrombopag (TPO receptor agonist) added to IST improves complete response rates
- Risk of relapse (~30%) and clonal evolution to MDS/AML (~10-15% at 10 years)
4
Remove causative agent
- Stop any potentially causative drugs immediately
- Treat underlying infection if identified
Complications
- Neutropenic sepsis: Life-threatening — the major acute risk in severe aplastic anaemia
- Haemorrhage: From thrombocytopenia — intracranial haemorrhage is the most feared complication
- Clonal evolution: 10-15% of patients develop MDS or AML over 10 years — requires long-term surveillance
- PNH: Paroxysmal nocturnal haemoglobinuria may develop in up to 50% of aplastic anaemia patients
- Iron overload: From chronic red cell transfusions — requires chelation
UKMLA Exam Tips
- 1Pancytopenia + hypocellular marrow = aplastic anaemia. Pancytopenia + blasts = leukaemia. Pancytopenia + dysplasia = MDS
- 2NO hepatosplenomegaly or lymphadenopathy — this distinguishes aplastic anaemia from leukaemia/lymphoma
- 3Drug causes to remember: chloramphenicol, carbamazepine, gold, sulphonamides, NSAIDs
- 4Always screen for PNH clone — aplastic anaemia and PNH share a pathological relationship
- 5Young + matched sibling donor → transplant. Older + no donor → ATG + ciclosporin + eltrombopag
- 6Fanconi anaemia: inherited cause in children — short stature, absent thumbs, café-au-lait spots, chromosomal fragility
practicetest your knowledge on aplastic anaemiaApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — haematology and beyond.
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