Case 28 – update 2

We had a busy week this week, but have established a diagnosis of Aplastic Anaemia for our young woman. Please see our latest storify if you are interested in our how our discussion evolved ( although I will summarise below:

We diagnosed Aplastic Anaemia by ruling out Fanconi Anaemia (we should also have ruled out a number of other inherited bone marrow disorders; see below). We also established that she had only low-level EBV viraemia and did not, on microbiological advice, feel this could have caused her pancytopenia. We then did a bone marrow biopsy and found her marrow to be empty:


We clearly have some work ahead of us now. The questions we need to consider at the start of this week are:

1) Do cytogenetic results matter here? If so, how would they influence our management?

2) What are the treatment options available to the patient? We are all working in different countries – what are the first and second line therapies in this situation? What influences these decisions?

3) As a haematology nurse (if that is what you are) what advice do you need to be giving this patient? What issues and concerns do you find most commonly arise in the minds of young patients with such a serious diagnosis?

Please reply via Twitter and REMEMBER TO USE THE HASHTAG! #teamhaem

Everyone has a different perspective and we want to hear from you all – saving lives is a multidisciplinary effort! 

As ever be aware that we use entirely fictional cases to maintain patient confidentiality. We are not a haematological authority but rather run an educational platform to bring haematology joy to the world…

Other notes on Aplastic Anaemia

A more comprehensive list of differentials for pancytopenia, not all of which apply to our patient, include:

  • Haemophagocytosis
  • Myelodysplasia (Hyoplastic variant)
  • PNH (overlap is common)
  • TB/mycobacteria – causing haemophagocytosis, necrotic BM with granuloma
  • B12/folate deficiency
  • Hairy Cell Leukaemia
  • Hypocellular ALL
  • SLE – AI pancytopenia with normal BM
  • myelofibrosis

There are congenital conditions that can lead to Aplastic Anaemia which include:

Dyskeratosis Congenita:

  • A telomeropathy
  • might be suggested by a FH of BMF/leukaemia, abnormal nails/skin/leukoplakia, pulmonary fibrosis, cirrhosis.
  • Measurement of telomere length of lymphocytes  can be done using FISH
    • Distinguishes dyskeratosis congenita (DC) from AA
    • Abnormally short telomeres of lymphocytes = sensitive + specific for DC
  • Screening for mutations in telomerase genes is also useful(DKC1, TERT, TERC)
    • DKC1, TERC, TINF2, NOP10, TERT mutations = Dyskeratosis Congenita
    • TERT / TERC mutations = Aplastic Anaemia

Fanconi’s Anaemia

  • Genetically and phenotypically heterogenous

–Mitomycin chromosomal fragility tested; molecular abnormalities also sought.

There are associated physical/skeletal abnormalities including ‘elfin’ facies, , short stature, ENT defects.

  • Marrow failure will evolve–progressively increased risk with age.
  • Radiation/alkylating agent sensitivity – therefore BMT conditioning protocols are very different in this population
  • Cancer predisposition is lifelong requiring meticulous monitoring:
    • squamous (ENT; anogenital) Hepatic carcinomas = most common

Schwachman Diamond Syndrome

  • Exocrine pancreatic dysfunction
  • Marrow dysfunction

–Neutropenia, pancytopenia, MDS/Leuk predisposition

  • Skeletal abnormalities
  • immunodeficiency
  • Failure to thrive; diarrhoea
    • Faecal elastase measurement
    • Molecular testing (SBDS gene – Manchester test for the UK)
    • Arch Dis childhood Guideline is excellent

Pearson Syndrome

  • Exocrine pancreatic dysfunction
  • Refractory sideroblastic anaemia; vacuolated myeloid cells
  • Mitochondrial dysfunction
  • Physical abnormalities rare
  • Median survival 3yr (metabolic acidosis)

CAMT (congenital amegakaryocytic thrombocytopenia)

These patients are diagnosed due to severe persistent thrombocytopenia; investigations reveal an absence of megakaryocytes in the marrow. These patients require bone marrow transplantation for long term survival. A small number may develop aplastic anaemia.

There are numerous other disorders that affect haematopoieisis but do not cause pancytopenia, eg

Diamond Blackfan Anaemia and Congenital Dyserythropoietic Anaemias – isolated abnormalities of erythropoiesis

TAR (Thrombocytopenia with absent radii), Wiscott Aldrich Synrome, May-Hegglin Syndrome – all affect megakaryopoiesis with no disorder of the other lineages.

It should be noted that PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA is closely associated with Aplastic Anaemia – but we will cover this in another case.

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Online education and discussion about all things haematological
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