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Perth Haematology :: Dr Steven Ward

Aplastic Anaemia

 

 

Aplastic Anaemia

Aplastic Anaemia (AA) = An acquired disorder of the marrow, characterised by marrow failure causing low blood counts (pancytopenia) without an abnormal infiltrate or increased fibrosis. The marrow is empty of precursor cells, leading to insufficient blood cells in the circulation. The severity can vary greatly, and can change within an individual.

 

It is rare with an incidence of 0.2/100,000 per year

 

It is not a form of leukaemia or cancer.

 

There are other forms of marrow aplasia due to other conditions. These conditions have to be ruled-out in order to make the diagnosis of acquired Aplastic Anaemia.

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“inevitable marrow failure (aplasia)”: following high-dose chemotherapy or radiation

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Rare inherited aplastic anaemias: Fanconi Anaemia

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Rarely acute leukaemia will present with AA, more usually the marrow is packed full of leukaemic blast cells

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Hypoplastic myelodysplasia (MDS) can be difficult to separate from acquired AA as marrow failure also occurs, but usually with an overactive marrow. Occasionally the marrow is also aplastic.

 

Causes of AA

Auto-immune reaction: the immune system starts attacking it’s own cells (in this case the marrow stem cells). 75% are of unknown cause (“idiopathic”). The remaining cases have an identifiable trigger-factor such as certain drugs, viruses, chemicals, pregnancy.

 

Clinical Features:

There may be no symptoms, with the disease found incidently
None of the symptoms are specific for AA and may be due to other problems


Symptoms related to marrow failure:

bulletLack of normal white cells: infection, fever
bulletLack of red cells and Hb: anaemia - tired, breathless, pale
bulletLack of platelets: abnormal bruising and bleeding

 

Diagnosis:

This is based on the low blood counts – usually all three counts are low

reticulocyte count will be low – this measures now juvenile red blood cells

Bone Marrow aspirate and trephine – this will show an “empty” marrow with increased fat and no fibrosis. Often 2 separate marrow studies from different sites are required to confirm the diagnosis. The absence of leukaemia cells is carefully examined

 

 

Severity

Very Severe AA (VSAA):

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BM cellularity < 25% (or 25-50% with <30% residual haemopoietic cells)

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Low platelets < 20 x 109/L

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Retic count <20 x 109/L (<1%)

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Absolute neutrophil count (ANC) < 0.2 x 109/L

 

Severe AA (SAA):
As for VSAA but ANC between 0.2 and < 0.5 x 109/L

 

Non-Severe AA (NSAA)

Blood counts higher than above but below normal.

Hb < 100;  Plat <50; ANC < 1.5

 

Treatment

Supportive Care: aimed at treating the consequences of low blood counts:

Transfusion of blood (red cells); platelets and antibiotics for infections. The need for transfusion depends on the blood level and the symptoms associated with that level. All transfusions should be very carefully considered as frequent transfusion can lead to antibody formation against the transfused cells, making further transfusion or bone marrow transplant more difficult.

 

Definitive therapy: aimed at treating the AA itself and restoring marrow function.

Treatment often takes months to reach maximum benefit. The outlook for Severe or Very Severe AA is poor without some form of therapy. Death occurs due to bleeding or infection.

 

Definitive therapy is aimed at suppressing the immune system, and allowing normal stem cells to develop and form blood cells.

 

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Stem cell Transplant: This is the only potentially curative therapy for Severe and Very Severe AA. The marrow is replaced by someone else’s marrow thus providing undamaged stem cells and a new immune system (which will not attack the stem cells). Usually a brother or sister’s marrow is used, if they are compatible.

 

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Immunosuppression: This is used when a transplant is not possible or not an option
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Anti-Thymocyte Globulin (ATG): this is antibody directed against lymphoid cells of the immune system, and wipes these out, leading to reduced antibody against the marrow stem cells, and increased function of the marrow. ATG is prepared in horses and can cause allergic or serum sickness reactions.

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Anabolic steroids: limited benefit, usually in mild cases

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Cyclosporin: this agent is useful in AA, usually used in combination with ATG.

 

 

 

Follow-up

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Over half of patients treated with immunosuppression do well, with adequate (but often not quite normalised) blood counts, without the need for transfusion.

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The other half develop a change or relapse at some time, which may be many years later.

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20-30% will go on to develop a new blood disorder: perhaps myelodysplasia, acute leukaemia or PNH.