A 68 yr old critically ill man with pulmonary  infiltrates  has the following haematology results.

Haemoglobin

79

(130-170 g/L)

Mean Corpuscular Volume

83.8

(80-96 fL)

White Cell Count

1.5

(4.0-11.0 x10^9/L)

Platelets

47

(140-400x10^12/L)

What is the haematological diagnosis? 

 List three potential causes of the haematological abnormalities?  

Outline what relevant information could be obtained from a bone marrow biopsy in this case.

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College Answer

The  haematologic term  is  pancytopenia (sometimes called “aplastic anaemia”, but  this subset really requires demonstration of an empty bone marrow).

Potential  causes  include  aplastic  anaemia  (eg.  external  radiation,  drugs  [eg. chloramphenicol, sulphonamides etc.], toxins [eg. benzene]), replacement of marrow (eg. with malignant cells), megaloblastic hematopoiesis, myelodysplastic syndrome, and overwhelming infections.

Bone marrow biopsy would confirm diagnosis and allow therapy to be targeted. It would assess marrow cellularity, identify normality or otherwise of haematopoietic cells (eg. megaloblastic change), demonstrate infiltration or fibrosis, or macrophages engorged with haematopoietic cells (viral hemophagocytic syndrome).

Discussion

This gentleman seems to have a normocytic anaemia with the WCC and platelet lineages also in decline. The college calls it pancytopenia, which is a reasonable term. Kufe et al have an excellent book chapter (2003) on the oncological causes of pancytopenia, which are probably the most community-prevalent sort of causes (given that practically nobody gets chloramphenicol in those sorts of doses anymore, and that here in sunny Australia we don't see much radiation sickness).

However, the savvy exam candidate is expected to generate a torrential stream of differentials.

A 2013 article by Weinzierl et al arms the candidate with an exhaustingly vast list of potential aetiologies. In the interest of sanity, the list was abridged before being reproduced 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
  • 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

Bone marrow biopsy is indeed 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.

References

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.