Question 25 from the first paper of 2005 asked the candidates to arrive at a series of sensible differentials to explain a case of pancytopenia in a 68 year old man with diffuse bilateral pulmonary infiltrates. Question 23.3 from the second paper of 2015 examines the cause of a pancytopenia in a patient with multi-organ system failure in the context of pneumonia and sepsis.

Readable literature for this topic needs to include the following sources:

  • Kufe et al (2003) on the oncological causes of pancytopenia
  • Weinzierl et al (2013) for a list of (many) other causes

These have been condensed into the table offered below:

Differential Diagnosis of Pancytopenia
  • Infectious causes
    • EBV
    • HIV
    • Hep A, B, C
    • Parvovirus
    • CMV
    • Dengue fever
  • Neoplastic causes
    • Leukaemia
    • Marrow involvement from solid tumours
  • Drugs which cause pancytopenia
    • Methyldopa
    • Carbimazole
    • Acetazolamide
    • Chloramphenicol
    • Trimethoprim/sulfamethoxazole
    • Carbamazepine
    • Cytotoxic agents
  • Idiopathic causes
    • Pregnancy (may be a coincidental association)
    • Splenomegaly (sequestration)
    • Anorexia nervosa
    • Malnutrition
    • Myelofibrosis
    • Paroxysmal nocturnal haemoglobinuria
  • Congenital causes
    • Haemophagocytic lymphohistiocytosis
    • Fanconi anaemia
    • Shwachman-Diamond syndrome
  • Autoimmune causes
    • SLE
  • Traumatic causes
    • Radiation toxicity

Bone marrow biopsy is the investigation of choice for pancytopenia.

It will rapidly narrow the list of differentials, at least if one is able to catch some cells in one's sample. Occasionally, one finds a pocket of totally acellular marrow, which - though ominously prognostic - is frequently useless diagnostically.  The most likely cause of pancytopenia is acute lymphoblastic leukaemia in children and acute myeloid leukaemia/myelodysplastic syndrome in adults.

References

Kufe, Donald W., et al. "Causes of Pancytopenia." (2003). Holland-Frei Cancer Medicine. 6th edition. Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Hamilton (ON): BC Decker; 2003.

Khodke, Kishor, et al. "Bone marrow examination in cases of pancytopenia."Indian Academy of Clinical Medicine 2 (2001): 1-2.

Gayathri, B. N., and Kadam Satyanarayan Rao. "Pancytopenia: A clinico hematological study." Journal of laboratory physicians 3.1 (2011): 15.

Weinzierl, Elizabeth P., and Daniel A. Arber. "The differential diagnosis and bone marrow evaluation of new-onset pancytopenia." American journal of clinical pathology 139.1 (2013): 9-29.

Marsh, Judith CW, et al. "Guidelines for the diagnosis and management of aplastic anaemia." British journal of haematology 147.1 (2009): 43-70.