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Aplastic Anaemia & PNH for MRCP Part 1

TL;DR

Bone marrow failure syndromes—especially aplastic anaemia and paroxysmal nocturnal haemoglobinuria (PNH)—are frequently tested in MRCP Part 1 due to their overlapping features and distinctive diagnostic clues. Focus on pancytopenia patterns, haemolysis markers, and confirmatory tests like flow cytometry. Recognising key differences (e.g. hypocellular marrow vs complement-mediated haemolysis) is essential for exam success. This guide distils high-yield facts, pitfalls, and exam strategies.


Why this matters

Bone marrow failure is a high-yield MRCP Part 1 topic that tests your ability to distinguish between production failure and haemolysis. Aplastic anaemia and PNH often appear in exam stems with subtle overlapping features—yet require very different diagnostic approaches.

You are expected to:

  • Interpret cytopenias and reticulocyte counts

  • Identify diagnostic tests (bone marrow biopsy vs flow cytometry)

  • Recognise life-threatening complications (infection, thrombosis)

For a structured revision roadmap, start with the MRCP Part 1 overview.


Core sections

1. Aplastic Anaemia — Mechanism & Features

Aplastic anaemia is characterised by immune-mediated destruction of haematopoietic stem cells, leading to bone marrow failure.

High-yield features:

  • Pancytopenia (anaemia, neutropenia, thrombocytopenia)

  • Low reticulocyte count

  • Hypocellular bone marrow (fatty replacement)

  • No splenomegaly (key exam clue)

Common causes:

  • Idiopathic (most common)

  • Drugs: chloramphenicol, carbamazepine

  • Viral: hepatitis, EBV, parvovirus B19

2. PNH — Mechanism & Features

PNH is a clonal stem cell disorder caused by a PIGA gene mutation, resulting in deficiency of GPI-anchored proteins.

High-yield features:

  • Intravascular haemolysis → haemoglobinuria (dark urine, morning)

  • Raised LDH, low haptoglobin

  • Thrombosis in unusual sites (hepatic, portal veins)

  • Coombs-negative haemolysis

Diagnostic hallmark:

  • Flow cytometry showing loss of CD55 and CD59

3. Aplastic Anaemia vs PNH (Exam Table)

Feature

Aplastic Anaemia

PNH

Pathophysiology

Stem cell destruction

Complement-mediated haemolysis

Blood counts

Pancytopenia

Variable cytopenias

Reticulocytes

Low

Normal/high

Bone marrow

Hypocellular

Often normal

Haemolysis

Absent

Present

Key test

Bone marrow biopsy

Flow cytometry

Splenomegaly

Absent

Usually absent

Complication

Infection, bleeding

Thrombosis

4. Five Most Tested Subtopics

1. Pancytopenia interpretation

  • Aplastic anaemia → low reticulocytes

  • PNH → haemolysis markers present

2. Flow cytometry

  • Gold standard for PNH

  • Detects absence of CD55/CD59

3. Thrombosis in PNH

  • Occurs in unusual venous sites

  • Major cause of mortality

4. Treatment principles

  • Aplastic anaemia → ATG + ciclosporin or transplant

  • PNH → eculizumab (anti-C5 monoclonal antibody)

5. Overlap syndromes

  • PNH clones may arise in aplastic anaemia

  • Frequently tested association

5. Eight High-Yield Exam Points

  1. No splenomegaly = think aplastic anaemia

  2. Morning haemoglobinuria = classic PNH clue

  3. Low reticulocytes = marrow failure

  4. High LDH + low haptoglobin = haemolysis

  5. CD55/CD59 deficiency confirms PNH

  6. Thrombosis in hepatic veins = PNH hallmark

  7. Hypocellular marrow = aplastic anaemia

  8. Eculizumab reduces haemolysis and thrombosis in PNH

Medical student revising haematology notes for MRCP Part 1 exam preparation

Practical examples / mini-cases

Case

A 28-year-old woman presents with fatigue and recurrent infections. Blood tests show pancytopenia with low reticulocyte count. There is no splenomegaly.

Most likely diagnosis? A. PNHB. Aplastic anaemiaC. Autoimmune haemolytic anaemiaD. Myelofibrosis

Answer: B — Aplastic anaemia

Explanation: Pancytopenia with low reticulocytes and no splenomegaly strongly suggests aplastic anaemia. PNH would show haemolysis and often haemoglobinuria.


Practical study-tip checklist

  • ✔ Classify cytopenias: production vs destruction

  • ✔ Memorise CD55/CD59 = PNH

  • ✔ Associate thrombosis with PNH

  • ✔ Link hypocellular marrow to aplastic anaemia

  • ✔ Practise regularly using Free MRCP MCQs

  • ✔ Simulate exam conditions via Start a mock test

  • ✔ Focus on lab-based questions

  • ✔ Revise overlap syndromes


Common pitfalls

  • Confusing PNH with autoimmune haemolysis (Coombs negative in PNH)

  • Missing thrombosis risk in PNH

  • Assuming splenomegaly in aplastic anaemia

  • Forgetting flow cytometry as diagnostic gold standard

  • Ignoring reticulocyte count in marrow failure


FAQs

1. How do you differentiate aplastic anaemia from PNH?

Aplastic anaemia presents with pancytopenia and hypocellular marrow without haemolysis. PNH shows haemolysis, thrombosis, and CD55/CD59 deficiency.

2. What is the most important test for PNH?

Flow cytometry demonstrating absence of CD55 and CD59 on red blood cells.

3. Why is thrombosis common in PNH?

Complement activation leads to platelet activation and a prothrombotic state, especially in unusual venous sites.

4. What is the first-line treatment for aplastic anaemia?

Immunosuppressive therapy (ATG + ciclosporin) or stem cell transplantation in eligible patients.

5. Can aplastic anaemia and PNH overlap?

Yes, PNH clones may develop in aplastic anaemia, making this a common exam scenario.


Ready to start?

Consolidate your understanding of marrow failure syndromes with active recall and question practice. Begin with the MRCP Part 1 overview and reinforce learning using the QBank and mock tests.

For deeper integration, pair this with haemolytic anaemia revision topics within your study plan.


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