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Chapter 22 Aplastic anaemia and bone marrow failure / 289

Pancytopenia Pathogenesis
Pancytopenia is a reduction in the blood count of Th e underlying defect in all cases appears to be a
all the major cell lines – red cells, white cells and substantial reduction in the number of haemopoi-
platelets. It has several causes (Table 22.1 ) which etic pluripotential stem cells, and a fault in the
can be broadly divided into decreased bone marrow remaining stem cells or an immune reaction against
production or increased peripheral destruction. them, which makes them unable to divide and dif-
ferentiate sufficiently to populate the bone marrow

(Fig. 22.1 ). A primary fault in the marrow micro-
Aplastic a naemia
environment has also been suggested but the success
Aplastic (hypoplastic) anaemia is defined as pancy- of stem cell transplantation (SCT) shows this can

topenia resulting from aplasia of the bone marrow. only be a rare cause because normal donor stem cells
It is classifi ed into primary (congenital or acquired) are usually able to thrive in the recipient ’ s marrow
or secondary types (Table 22.2 ). cavity.

Congenital

Table 22.1 Causes of pancytopenia. The Fanconi type has an autosomal recessive pattern

of inheritance and is often associated with growth
Decreased bone marrow function
retardation and congenital defects of the skeleton
Aplasia
(e.g. microcephaly, absent radii or thumbs), of the
Acute leukaemia, myelodysplasia, myeloma
renal tract (e.g. pelvic or horseshoe kidney) (Fig.
Infi ltration with lymphoma, solid tumours, 22.2 ) or skin (areas of hyper - and hypopigmenta-
tuberculosis
tion); sometimes there is mental retardation. Th e
Megaloblastic anaemia

syndrome is genetically heterogeneous with 13 dif-
Paroxysmal nocturnal haemoglobinuria
ferent genes involved, A, B, C, D1, D2, E, F, G, I,
Myelofi brosis
J, L, M and N in different families. Th e encoded

Haemophagocytic syndrome
proteins cooperate in a common cellular pathway
Increased peripheral destruction
which results in ubiquitination of FANCD2, which
Splenomegaly
protects cells against genetic damage.

Table 22.2 Causes of aplastic anaemia.
Primary Secondary
Congenital (Fanconi and Ionizing radiation : Accidental exposure (radiotherapy, radioactive
non - Fanconi types) isotopes, nuclear power stations)
Idiopathic acquired Chemicals : Benzene, organophosphates and other organic solvents, DDT
and other pesticides, organochlorines, recreational drugs (ecstasy)
Drugs : Those that regularly cause marrow depression (e.g. busulfan,
melphalan, cyclophosphamide, anthracyclines, nitrosoureas).
Those that occasionally or rarely cause marrow depression (e.g.
chloramphenicol, sulphonamides, gold, anti - infl ammatory, antithyroid,
psychotropic, anticonvulsant/antidepressant drugs)
Viruses : Viral hepatitis (non - A, non - B, non - C, in most cases), EBV

EBV, Epstein – Barr virus.