Tests

1st tests to order

complete blood count and peripheral blood smear

Test
Result
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 anemia 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 <10 g/dL, platelet <50 × 10³/microliter (<50 × 10⁹/L), and/or absolute neutrophil count <1500/microliter (<1.5 × 10⁹/L); blood film: often normocytic or mild macrocytosis and anisopoikilocytosis

reticulocyte count

Test
Result
Test

A low reticulocyte count identifies that anemia is hypoproductive, as opposed to hyperproductive anemias such as hemolytic anemia.

Result

corrected reticulocyte percentage <1% or absolute reticulocyte count <60 × 10³/microliter (<60 x 10⁹/L) (using an automated analysis)

bone marrow biopsy and cytogenetic analyses

Test
Result
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

Tests to consider

serum B12 and folate levels

Test
Result
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
Result
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)

Test
Result
Test

Abnormal LFTs may suggest an inherited syndrome (dyskeratosis congenita or Shwachman-Diamond syndrome), recent hepatitis, or exposure to toxins.[8][9] Elevated lactate dehydrogenase suggests hemolysis.

Result

usually normal

autoantibody screen

Test
Result
Test

May indicate an associated autoimmune disorder. Anecdotal reports exist for an association between AA and systemic lupus erythematosus, thymoma, eosinophilic fasciitis, and celiac disease.[41][42]​​​[43]​​[44]​​​ The mechanism underlying this association is unclear.

Result

usually normal

flow cytometry for glycosylphosphatidylinositol-anchored proteins

Test
Result
Test

One meta-analysis found that paroxysmal nocturnal hemoglobinuria clones were present in 37% of patients with AA pretreatment.[49]

Result

variable

chest x-ray

Test
Result
Test

Ordered if malignancy, infection, or lung fibrosis is suspected.

Result

normal, unless infection is present

abdominal ultrasound

Test
Result
Test

Ordered if malignancy, Fanconi anemia, or telomeropathy is suspected.

Abnormal or displaced kidneys may be seen in Fanconi anemia.

Splenomegaly or lymphadenopathy raises possibility of a hematologic malignancy rather than aplastic anemia (AA).

Liver cirrhosis/fibrosis suggests telomeropathies.

Result

variable

appropriate genetic tests

Test
Result
Test

If a congenital syndrome is suspected, appropriate diagnostic tests should be obtained: for example, chromosomal breakage testing (diepoxybutane test) for Fanconi anemia; 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 centers.

Inherited marrow failure syndrome gene panels with next-generation sequencing are available at some specialist centers. They can be used to identify telomeropathies, mutations, and malignancies.[25]

Result

may be positive

computed tomography scan

Test
Result
Test

Ordered if telomeropathies or dyskeratosis congenita is suspected.

Lung fibrosis, cirrhosis, or noncirrhotic portal hypertension may suggest dyskeratosis congenita.

Result

variable

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