Page 306 - Essential Haematology

292 / Chapter 22 Aplastic anaemia and bone marrow failure

Idiopathic a cquired insidious or acute with symptoms and signs result-
ing from anaemia, neutropenia or thrombocytope-

This is the most common type of aplastic anaemia,
nia. Infections, particularly of the mouth and
accounting for at least two - thirds of acquired cases.
throat, are common and generalized infections are
In most cases haemopoetic tissue is the target of an
frequently life - threatening. Bruising, bleeding
immune process dominated by oligoclonal expres-
gums, epistaxes and menorrhagia are the most fre-
sion of cytotoxic T cells which secrete γ - interferon
quent haemorrhagic manifestations and the usual
and tumour necrosis factor. In approximately one -
presenting features, often with symptoms of
third of cases short telomeres are found in leuco-

anaemia. The lymph nodes, liver and spleen are not
cytes, especially in those with a prolonged clinical
enlarged.
course. Mutations in the telomere repair complex
have been described but their relevance is unclear.

The favourable responses to antilymphocyte globu- Laboratory fi ndings

lin (ALG) and ciclosporin support the concept that 1 Anaemia is normochromic, normocytic or mac-

autoimmune T - cell mediated damage, possibly rocytic (mean cell volume often 95 – 110 fL). Th e
against functionally and structurally altered stem reticulocyte count is usually extremely low in
cells, is important. relation to the degree of anaemia.
2 Leucopenia. There is a selective fall in granulo-

9
cytes, usually but not always to below 1.5 × 10 /L.
Secondary
In severe cases, the lymphocyte count is also low.

This is often caused by direct damage to the haemo- The neutrophils appear normal.

poietic marrow by radiation or cytotoxic drugs. Th e 3 Th rombocytopenia is always present and, in
9
antimetabolite drugs (e.g. methotrexate) and mitotic severe cases, is less than 20 × 10 /L.

inhibitors (e.g. daunorubicin) cause only temporary 4 Th ere are no abnormal cells in the peripheral
aplasia but the alkylating agents, particularly busul- blood.
fan, may cause chronic aplasia closely resembling the 5 Th e bone marrow shows hypoplasia, with loss of
chronic idiopathic disease. Some individuals develop haemopoietic tissue and replacement by fat
aplastic anaemia as a rare idiosyncratic side - eff ect of which comprises over 75% of the marrow.
drugs such as chloramphenicol or gold which are not Trephine biopsy is essential and may show patchy
known to be cytotoxic (Table 22.2 ). They may also cellular areas in a hypocellular background (Fig.

develop the disease, during or within a few months 22.1 b). The main cells present are lymphocytes

of, viral hepatitis (rarely hepatitis A, B or C, but and plasma cells; megakaryocytes in particular
more frequently non - A, non - B, non - C). Because the are severely reduced or absent.
incidence of marrow toxicity is particularly high for 9
Severe cases show neutrophils < 0.5 × 10 /L (very
chloramphenicol, this drug should be reserved for 9 9
severe < 0.2 × 10 /L), platelets < 20 × 10 /L, reticu-
treatment of those infections that are life - threaten- 9
locytes < 20 × 10 /L and marrow cellularity < 25%.
ing and for which it is the optimum antibiotic (e.g.
typhoid). Chemicals such as benzene may be impli-
cated and rarely aplastic anaemia may be the pre- Diagnosis
senting feature of acute lymphoblastic or myeloid The disease must be distinguished from other causes

leukaemia, especially in childhood. Myelodysplasia of pancytopenia (Table 22.1 ) and this is not usually
(see Chapter 16 ) may also present with a hypoplastic difficult provided an adequate bone marrow sample

marrow. is obtained. Cytogenetic analysis should be per-
formed. Paroxysmal nocturnal haemoglobinuria

(PNH) must be excluded by flow - cytometry testing
Clinical f eatures
of red cells for CD55 and CD59. In older patients,
The onset is at any age with a peak incidence around hypoplastic myelodysplasia may show similar

30 years and a slight male predominance; it can be appearances. Qualitative abnormalities of the cells