Investigations
1st investigations to order
full blood count and peripheral blood smear
Test
Pancytopenia is common, but the diagnosis of AA requires only two cytopenias among white cell, red cell, and platelet lineages.
Presence of macrocytosis may suggest inherited syndrome (Fanconi anaemia or dyskeratosis congenita).
Presence of monocytopenia may indicate inherited GATA2-related disorder.
The presence of abnormal cells or dysplasia suggests an alternative diagnosis.[1]
Result
≥2 cytopenias among the following: Hb <100 g/L (<10 g/dL), platelet <50 × 10⁹/L (<50 × 10³/microlitre), and/or absolute neutrophil count <1.5 × 10⁹/L (<1500/microlitre); blood film: often normocytic or mild macrocytosis and anisopoikilocytosis
reticulocyte count
Test
A low reticulocyte count identifies that anaemia is hypoproductive, as opposed to hyperproductive anaemias such as haemolytic anaemia.
Result
corrected reticulocyte percentage <1% or absolute reticulocyte count <60 x 10⁹/L (<60 × 10³/microlitre) (using an automated analysis)
bone marrow biopsy and cytogenetic analyses
Test
A hypocellular marrow is a definitive diagnostic finding for AA. Moreover, there should be an absence of abnormal cell population (such as blasts) and no fibrosis.
Result
hypocellular marrow with no abnormal cell population
Investigations to consider
serum B12 and folate levels
Test
Severe vitamin B12 and/or folate deficiency may be an alternative cause of pancytopenia but should not preclude or delay bone marrow analysis.
Result
normal
virus testing
Test
Testing for HIV, hepatitis A/B/C/E, Epstein-Barr virus, cytomegalovirus, and parvovirus B19 may be undertaken. HIV infection may be an alternative cause of pancytopenia. Virus testing should not preclude or delay bone marrow analysis.
Result
negative
liver function tests (LFTs)
autoantibody screen
flow cytometry for glycosylphosphatidylinositol-anchored proteins
Test
One meta-analysis found that paroxysmal nocturnal haemoglobinuria clones were present in 37% of patients with AA pre-treatment.[49]
Result
variable
chest x-ray
Test
Ordered if malignancy, infection, or lung fibrosis is suspected.
Result
normal, unless infection is present
abdominal ultrasound
Test
Ordered if malignancy, Fanconi anaemia, or telomeropathy is suspected.
Abnormal or displaced kidneys may be seen in Fanconi anaemia.
Splenomegaly or lymphadenopathy raises possibility of a haematological malignancy rather than aplastic anaemia (AA).
Liver cirrhosis/fibrosis suggests telomeropathies.
Result
variable
appropriate genetic tests
Test
If a congenital syndrome is suspected, appropriate diagnostic tests should be obtained: for example, chromosomal breakage testing (diepoxybutane test) for Fanconi anaemia; relevant genetic sequencing for other disorders, such as TERC, TERT, TINF2, DKC1 (for dyskeratosis congenita), SBDS (for Shwachman-Diamond syndrome), and GATA2 (for inherited GATA2-related disorder) and other germline mutations (e.g.,SAMD9/SAMD9L, DDX41, ERCC6L2). Telomeropathies are screened for by measuring telomere length.
Telomere length below first percentile indicates telomeropathies, although this test is not routinely available in many centres.
Inherited marrow failure syndrome gene panels with next-generation sequencing are available at some specialist centres. They can be used to identify telomeropathies, mutations, and malignancies.[25]
Result
may be positive
computed tomography scan
Test
Ordered if telomeropathies or dyskeratosis congenita is suspected.
Lung fibrosis, cirrhosis, or non-cirrhotic portal hypertension may suggest dyskeratosis congenita.
Result
variable
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