Pancytopenia

A deficiency of blood cells of all lineages (but generally excludes lymphocytes) - not a diagnosis, and does not always mean bone marrow failure or malignancy

Aetiology

Reduced production - bone marrow failure

  • Inherited syndromes - very rare
    • Characterised by impaired haeopoiesis, congenital abnormalities and cancer predisposition
    • Arise due to defects in DNA repair/ribosomes/telomeres
    • Example: patients with Fanconi’s anaemia are unable to correct inter-strand cross-links (DNA damage)
  • Acquired
    • Primary - no obvious cause, usually stem cell defect
      • Idiopathic aplasic anaemia - autoreactive T-cells target haemapoeisis
      • Myelodysplastic syndromes - increased apoptosis of progenitor and mature cells, propensity for evolution into AML
      • Acute leukaemia (WCC can be variable) - proliferation of abnormal cells from LSC, failure to differentiate into mature or normal cells, prevent normal HSC development
    • Secondary
      • Drug induced e.g. chemotherapy, alcohol, azathioprine, metotrexate, chlorampenicol - causes aplasia
      • B12/folate deficiency - nuclear maturation can affect all lineages
      • Infiltrative - non-haemopoietic malignant infiltration, lymphoma
      • Misc. - viral (e.g. HIV), storage diseases

Increased destruction - hypersplenism

  • Pancytopenia can be caused by increased splenic pool or increased destruction that exceeds bone marrow capacity, usually associated with a significantly enlarged spleen
  • Causes of hypersplenism:
    • Splenic congestion e.g. portal hypertension
    • Systemic diseases e.g. rheumatoid arthritis
    • Haematological diseases e.g. splenic lymphoma

Pathophysology

Marrow cellularity in pancytopenia

  • Variable depending on the cause
  • Hypocellular in aplasic anaemia
  • Hypercellular in myelodysplastic syndromes, B12/folate deficiency, hypersplenism

Clinical presentation

  • Anaemia - fatigue, shortness of breath, cardiovascular compromise
  • Neutropenia - increased severity and duration of infections, opportunistic infections
  • Thrombocytopenia - bleeding (purpura, petechiae, ‘wet’ bleeds)
  • Presentation can also be influenced by underlying cause

Investigations

  • Bloods - FBC, blood film
  • Additional routine tests guided by history (inc. family history), clinical findings, and initial blood results
  • Bone marrow examination
  • Specliased tests guided by above e.g. cytogenetics (e.g. chromosome fragility testing in Fanconi’s syndrome, NGS, WES)

Management

Supportive

  • Transfusions - red cell transfusions, platelet transfusions, (neutrophil transfusions not routine)
  • Antibiotic prophylaxis/treatment where appropriate
  • Treat neutropenic fever promptly based on local unit antibiotic policy without waiting for microbiology results

Specific

  • Dependent on cause
Primary bone marrow disorder
  • Malignancy - consider chemotherapy
  • Congenital - consider bone marrow transplantation
  • Idiopathic aplastic anaemia - immunisuppression
Secondary bone marrow disorder
  • Drug reaction - STOP
  • Viral - e.g. treat HIV
  • Replace B12/folate
Hypersplenism
  • Treat cause if possible
  • Consider splenectomy (not appropriate in all cases)