Page 317 - Textbook of Pathology, 6th Edition

spontaneously in middle-aged and older individuals of both 301
sexes. The disorder has its pathogenesis in disturbed growth
and maturation of erythroid precursors at the level of
haematopoietic stem cell, possibly due to reduced activity
of the enzyme, ALA synthetase. The anaemia is of moderate
to severe degree and appears insidiously. The bone marrow
cells commonly show chromosomal abnormalities, neutro-
penia and thrombocytopenia with associated bleeding
diathesis. The spleen and liver may be either normal or mildly
enlarged, while the lymph nodes are not enlarged. Unlike
other types of sideroblastic anaemia, this type is regarded as
a myelodysplastic disorder in the FAB (French-American-
British) classification and thus, can be a preleukaemic
disorder (page 361). About 10% of individuals with refractory
acquired sideroblastic anaemia develop acute myelogenous
leukaemia. CHAPTER 12
B. Secondary acquired sideroblastic anaemia. Acquired
Figure 12.16 Sideroblastic anaemia bone marrow aspirate smear sideroblastic anaemia may develop secondary to a variety
in Perls’ stain shows marked excess of reticular iron and a ringed of drugs, chemicals, toxins, haematological and various other
sideroblast (arrow) showing Prusian blue granules in the cytoplasm.
diseases.
with Prussian blue reaction. Depending upon the number, 1. Drugs, chemicals and toxins: Isoniazid, an anti-tuberculous
size and distribution of siderotic granules, sideroblasts may drug and a pyridoxine antagonist, is most commonly
be normal or abnormal (Fig. 12.16). associated with development of sideroblastic anaemia by
Normal sideroblasts contain a few fine, scattered cytoplasmic producing abnormalities in pyridoxine metabolism. Other
granules representing iron which has not been utilised for drugs occasionally causing acquired sideroblastic anaemia
haemoglobin synthesis. These cells comprise 30-50% of are: cycloserine, chloramphenicol and alkylating agents (e.g.
normoblasts in the normal marrow but are reduced or absent cyclophosphamide). Alcohol and lead also cause
in iron deficiency. sideroblastic anaemia. All these agents cause reversible
sideroblastic anaemia which usually resolves following
Abnormal sideroblasts are further of 2 types: removal of the offending agent.
One type is a sideroblast containing numerous, diffusely
scattered, coarse cytoplasmic granules and are seen in 2. Haematological disorders: These include myelofibrosis,
conditions such as dyserythropoiesis and haemolysis. In this polycythaemia vera, acute leukaemia, myeloma, lymphoma
type, there is no defect of haem or globin synthesis but the and haemolytic anaemia.
percentage saturation of transferrin is increased. 3. Miscellaneous: Occasionally, secondary sideroblastic
The other type is ringed sideroblast in which haem anaemia may occur in association with a variety of inflam-
synthesis is disturbed as occurs in sideroblastic anaemias. matory, neoplastic and autoimmune diseases such as
Ringed sideroblasts contain numerous large granules, often carcinoma, myxoedema, rheumatoid arthritis and SLE. Introduction to Haematopoietic System and Disorders of Erythroid Series
forming a complete or partial ring around the nucleus. The
ringed arrangement of these granules is due to the presence Laboratory Findings
of iron-laden mitochondria around the nucleus. Sideroblastic anaemias usually show the following
haematological features:
Types of Sideroblastic Anaemias
1. There is generally moderate to severe degree of anaemia.
Based on etiology, sideroblastic anaemias are classified into
hereditary and acquired types. The acquired type is further 2.The blood picture shows hypochromic anaemia which
divided into primary and secondary forms: may be microcytic, or there may be some normocytic red
cells as well (dimorphic).
I. HEREDITARY SIDEROBLASTIC ANAEMIA. This is 3. Absolute values (MCV, MCH and MCHC) are reduced
a rare X-linked disorder associated with defective enzyme in hereditary type but MCV is often raised in acquired
activity of aminolevulinic acid (ALA) synthetase required for type.
haem synthesis. The affected males have moderate to marked
anaemia while the females are carriers of the disorder and 4. Bone marrow examination shows erythroid hyperplasia
do not develop anaemia. The condition manifests in with usually macronormoblastic erythropoiesis. Marrow
childhood or in early adult life. iron stores are raised and pathognomonic ring sideroblasts
are present.
II. ACQUIRED SIDEROBLASTIC ANAEMIA. The
acquired sideroblastic anaemias are classified into primary 5. Serum ferritin levels are raised.
and secondary types. 6. Serum iron is usually raised with almost complete
saturation of TIBC.
A. Primary acquired sideroblastic anaemia. Primary, idio-
pathic, or refractory acquired sideroblastic anaemia occurs 7. There is increased iron deposition in the tissue.