Differentials
Aplastic anaemia
SIGNS / SYMPTOMS
May have history of medications that cause aplastic anaemia; otherwise, symptoms may be the same.
INVESTIGATIONS
The marrow is hypocellular for age, and precursors are morphologically normal. There is no clonal chromosomal abnormality.
HIV infection
SIGNS / SYMPTOMS
History of HIV infection or activities that increase the risk of contracting HIV.
INVESTIGATIONS
HIV testing is positive.
Bone marrow may show some dysplastic cells, with erythroid and granulocytic precursors and megakaryocytes, but this is not usually a persistent finding and will change on repeat aspirate or biopsy.
Other viral infections (e.g., parvovirus, CMV, or hepatitis)
SIGNS / SYMPTOMS
May have viral prodromal symptoms or other symptoms specific to individual viral infection (e.g., jaundice with hepatitis).
INVESTIGATIONS
Positive test for viral infection.
Marked erythroid hypoplasia and occasional giant erythroblasts noted in bone marrow in parvovirus infection.
Intranuclear inclusions may be noted in CMV infection.
Acute myeloid leukaemia
SIGNS / SYMPTOMS
More likely to have: symptomatic cytopenia and leukocytosis; complications such as tumour lysis syndrome or disseminated intravascular coagulopathy; hepatosplenomegaly; and lymphadenopathy.
INVESTIGATIONS
Blasts ≥20%. Presence of AML-defining chromosomal abnormalities, irrespective of blast count (e.g., t(15;17)(q24.1;q21.2)/PML::RARA; t(8;21)(q22;q22.1)/RUNX1::RUNX1T1; inv(16)(p13.1q22); t(16;16)(p13.1;q22)/CBFB::MYH11; t(9;11)(p21.3;q23.3)/MLLT3::KMT2A; t(6;9)(p22.3;q34.1)/DEK::NUP214; inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/GATA2.[1]
Vitamin B12 deficiency
SIGNS / SYMPTOMS
History may highlight the underlying cause (e.g., bariatric surgery). In severe cases of vitamin B12 deficiency, symptoms such as glossitis, paraesthesia, and symptoms of subacute combined degeneration of cord may be present.
INVESTIGATIONS
Macrocytic anaemia will be present unless there is an associated iron deficiency.
Peripheral blood smear shows megaloblastic changes.
Serum vitamin B12 levels are low.
Folate deficiency
SIGNS / SYMPTOMS
History may highlight the underlying cause (e.g., use of methotrexate).
Painful swallowing, glossitis, and angular stomatitis may be present in patients with severe folate deficiency
INVESTIGATIONS
Macrocytic anaemia will be present unless there is an associated iron deficiency.
Peripheral blood smear shows megaloblastic changes.
Serum folate levels are low.
Myelofibrosis
SIGNS / SYMPTOMS
Splenomegaly is present in most patients. Some patients may have hepatomegaly.
INVESTIGATIONS
Bone marrow biopsy shows reticulin fibrosis.
Essential thrombocythaemia
SIGNS / SYMPTOMS
More commonly presents with vasomotor symptoms or complications from thrombosis or bleeding.
Livedo reticularis (a purplish mottled discolouration of the skin, usually on the legs, typically described as lacy or net-like in appearance) may be present.
INVESTIGATIONS
Elevated platelet count.
Bone marrow shows proliferation of the megakaryocyte lineage with increased numbers of enlarged, mature megakaryocytes with hyperlobulated nuclei, but does not show dysplasia.
Genetic testing may identify JAK2 V617F, CALR, or MPL mutations.
Large granular lymphocytic leukaemia (LGL)
SIGNS / SYMPTOMS
Splenomegaly and a history of autoimmune diseases may be present.
INVESTIGATIONS
Lymphocytosis is typical.
Large granular lymphocytes present on peripheral blood smear.
CD3+ cytotoxic T-cell clone present on flow cytometry.
Polymerase chain reaction may show T-cell receptor gene rearrangements in T-cell LGL.
Bone marrow toxicity secondary to azathioprine or cyclophosphamide
SIGNS / SYMPTOMS
May be undergoing treatment for lupus or rheumatoid arthritis.
INVESTIGATIONS
Reassess bone marrow aspirate for resolution of abnormalities after holding medication.
Bone marrow toxicity secondary to cytotoxic therapy (especially with alkylating drugs)
SIGNS / SYMPTOMS
History includes exposure to these medications.
INVESTIGATIONS
Reassess bone marrow aspirate for resolution of abnormalities after holding medication.
Heavy metal poisoning (particularly arsenic)
SIGNS / SYMPTOMS
History includes possible exposure, often occupational.
INVESTIGATIONS
Sideroblastic anaemia with no other marrow abnormalities and no abnormalities in other cell lines (normal platelets, WBC), abnormal heavy metal testing.
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