Aplastic anaemia is defined as pancytopenia with hypocellularity (aplasia) of the bone marrow. It is an uncommon but serious condition that may be inherited but is more commonly acquired.
Aplastic anaemia is due to a reduction in the number of pluripotential stem cells (see Fig. 6.1) together with a fault in those remaining or an immune reaction against them so that they are unable to repopulate the bone marrow. Failure of one cell line may occur resulting in isolated deficiencies such as the absence of red cell precursors in pure red cell aplasia.
A list of causes of aplasia is given. An immune mechanism is probably responsible for most cases of idiopathic acquired aplastic anaemia; immune suppression of stem cells by T suppressor cells has been implicated in many of these cases.
In contrast, secondary aplastic anaemia is due to direct damage to the bone marrow caused by drugs, chemicals, radiation or infection. Many drugs may cause marrow aplasia, including cytotoxic drugs such as busulphan and doxorubicin, which are expected to cause transient aplasia. However, some individuals develop aplasia after exposure to non-cytotoxic drugs such as chloramphenicol, gold, carbimazole, chlorpromazine, phenytoin, tolbutamide and many others which have been reported to cause occasional cases of aplasia. Congenital aplastic anaemias are rare. Fanconi’s anaemia is inherited as an autosomal recessive and is associated with skeletal, renal and central nervous system abnormalities. It usually presents between the ages of 5 and 10 years.
The clinical manifestations of marrow failure are anaemia, bleeding and infection. Physical findings include ecchymoses, bleeding gums and epistaxis. Mouth infections are common. Lymphadenopathy and hepatosplenomegaly are rare in aplastic anaemia.
The laboratory diagnosis is made on the basis of:
• The virtual absence of reticulocytes
• A hypo cellular or aplastic bone marrow with increased fat spaces
This is from other causes of pancytopenia. A bone marrow trephine is essential for assessment of the bone marrow cellularity.
TREATMENT AND PROGNOSIS
The cause of aplastic anaemia must be eliminated if possible. Supportive care including transfusions of red cells and platelets and antibiotic therapy should be given as necessary. The course of aplastic anaemia can be variable, ranging from a rapid spontaneous remission to a persistent increasingly severe pancytopenia, which may lead to death through haemorrhage or infection. The most reliable determinants for the prognosis are the number of neutrophils, reticulocytes, platelets, and the cellularity of the bone marrow.
Bad prognostic features
• A neutrophil count <0.5 x 109/litre
• A platelet count of <20 x 109/litre
• A reticulocyte count of 10 x 109/litre (0.1%)
• Severe hypo cellularity of the bone marrow
In severe aplastic anaemia (with three of the four bad prognostic features) there is less than 50% chance of survival beyond 6 months. Bone marrow transplantation is the treatment of choice for patients under 20 years of age who have an HLA-identical sibling donor. Older patients up to the age of 45 years with very severe aplastic anaemia (i.e. all the above criteria and a neutrophil count <0.2 x 109/litre) should also be treated by transplantation if an HLA-identical sibling is available. A successful graft occurs in 70-80% of patients. Patients between 20 and 45 years with severe aplastic anaemia might also be considered for bone marrow transplantation if an HLA-identical sibling is available, but, if not, treatment with immunosuppressive therapy is used.
About 70% of patients with aplastic anaemia eligible for bone marrow transplantation do not have an HLAidentical sibling. The results of bone marrow transplantation using unrelated donors or mismatched family donors is still too unsatisfactory to warrant its widespread use. Such treatment is currently restricted to very young patients «6 years) with severe aplastic anaemia and adults with very severe aplastic anaemia; both groups have a poor chance of survival if treated with immunosuppressive therapy. Patients failing to respond to immunosuppressive therapy may also be considered for this treatment.
Immunosuppressive therapy is used for those patients outlined above and for patients with severe aplastic anaemia over the age of 45 years; antilymphocyte globulin (ALG), steroids and cyclosporin are used alone or in combination. Patients over the age of 45 are not eligible for bone marrow transplantation whether an HLA-identical donor is available or not, because the high risk of graft-versus-host disease is a complication of bone marrowtransplantation. ALG alone produces a haematological recovery in 50-60% of cases and this is increased to 80% in patients receiving ALG, steroids and cyclosporin. Steroids are used to treat children with congenital pure red cell aplasia (Diamond-Blackfan syndrome). Adult pure red cell aplasia is associated with a thymoma in 30% of cases and thymectomy may induce a remission. It may also be associated with autoimmune disease or may be idiopathic. Steroids and cyclosporin are effective treatment in some cases.
Recombinant haemopoietic growth factors are being used in aplastic anaemia to prevent infective deaths in the early stages of treatment. It is unlikely that the use of haemopoietic growth factors will be effective as primary treatment for severe aplastic anaemia.