Pancytopenia is defined as a reduction in all three blood cell lines (red cells, white cells, and platelets) in peripheral blood. It reflects bone marrow dysfunction or destruction and is important to diagnose and manage appropriately for the UKMLA.

Aetiology:

1. Bone Marrow Failure:
   • Aplastic Anaemia:
     • Idiopathic (most common).
     • Secondary to drugs (e.g., chemotherapy, chloramphenicol), toxins, or infections (e.g., parvovirus B19, EBV, HIV).
   • Myelodysplastic Syndrome (MDS):
     • Dysplastic changes in bone marrow leading to ineffective haematopoiesis.
   • Leukaemia:
     • Infiltration of marrow by immature blasts (e.g., acute leukaemias).
   • Myelofibrosis:
     • Marrow fibrosis reducing haematopoiesis.
2. Bone Marrow Infiltration:
   • Malignancies (e.g., lymphoma, metastatic cancer).
   • Infections (e.g., tuberculosis, histoplasmosis).
   • Storage disorders (e.g., Gaucher’s disease).
3. Peripheral Destruction:
   • Hypersplenism:
     • Increased sequestration of blood cells in an enlarged spleen.
   • Autoimmune disorders (e.g., systemic lupus erythematosus).
4. Deficiencies:
   • Vitamin B12 or folate deficiency (megaloblastic anaemia).
5. Others:
   • Radiation exposure.
   • Paroxysmal nocturnal haemoglobinuria (PNH).

Clinical Features:

1. Symptoms of Anaemia:
   • Fatigue, pallor, dyspnoea.
2. Symptoms of Leukopenia:
   • Recurrent infections, fever.
3. Symptoms of Thrombocytopenia:
   • Easy bruising, petechiae, mucosal bleeding (e.g., epistaxis, gum bleeding).
4. Signs of Underlying Disease:
   • Splenomegaly (hypersplenism, infiltration).
   • Bone pain (leukaemia, myelofibrosis).
   • Weight loss, night sweats (malignancies).

Investigations:

1. Full Blood Count (FBC):
   • Reduction in haemoglobin, white cells, and platelets.
   • Mean cell volume (MCV) may help identify deficiencies (e.g., macrocytosis in B12 deficiency).
2. Peripheral Blood Film:
   • Blasts in leukaemia.
   • Macrocytes and hypersegmented neutrophils in megaloblastic anaemia.
3. Bone Marrow Aspiration/Biopsy:
   • Hypocellular marrow: Aplastic anaemia.
   • Hypercellular marrow with dysplasia: Myelodysplastic syndrome.
   • Infiltration: Leukaemia, lymphoma, or metastatic cancer.
4. Other Tests:
   • Vitamin B12 and folate levels.
   • Viral serologies (e.g., EBV, HIV, parvovirus B19).
   • Flow cytometry for PNH.
   • Imaging for splenomegaly or marrow infiltration.

Management:

1. Treat the Underlying Cause:
   • Aplastic Anaemia:
     • Immunosuppressive therapy (e.g., antithymocyte globulin, ciclosporin).
     • Bone marrow transplant (curative in young patients).
   • Leukaemia or MDS:
     • Chemotherapy or stem cell transplant.
   • Megaloblastic Anaemia:
     • Vitamin B12 or folate supplementation.
   • Infections:
     • Antiviral, antifungal, or antibiotic therapy.
2. Supportive Care:
   • Blood transfusions for anaemia.
   • Platelet transfusions for bleeding.
   • Prophylactic antibiotics and antifungals for neutropenia.
3. Other Therapies:
   • Eltrombopag:
     • Stimulates platelet production in aplastic anaemia.
   • Ruxolitinib:
     • JAK2 inhibitor for myelofibrosis.

Complications:

1. Severe Infections:
   • Due to neutropenia.
2. Bleeding:
   • Due to thrombocytopenia.
3. Progression to Acute Leukaemia:
   • Common in myelodysplastic syndrome.
4. Iron Overload:
   • From repeated transfusions.

Prognosis:

• Dependent on the underlying cause and treatment availability.
• Bone marrow transplant offers a potential cure for some cases of aplastic anaemia and leukaemia.

Key Exam Points for UKMLA:

1. Differential Diagnosis:
   • Recognise the broad range of causes and use investigations to narrow down the diagnosis.
2. Bone Marrow Findings:
   • Know the marrow appearance in different conditions (e.g., hypocellular in aplastic anaemia, hypercellular in leukaemia).
3. Management:
   • Focus on treating the underlying cause and providing supportive care.
4. Complications:
   • Recognise the risks of infection and bleeding in pancytopenia.