Lecture 12.sideroblastic anemia

2. Sideroblastic
Anaemia

3. Abnormal Accumulation
 Sideroblasts (sidero- + -blast) are atypical,
abnormal nucleated erythroblasts (precursors to mature
red blood cells) with granules of iron accumulated in
the mitochondria surrounding the nucleus.
 Pappenheimer bodies are abnormal granules of iron
found inside red blood cells on routine blood stain. They
are a type of inclusion body formed by phagosomes that
have engulfed excessive amounts of iron .
 Basophilic stippling : Coarse basophilic
stipplingindicates impaired hemoglobin synthesis,
probably due to the instability of RNA in the young cell.

4.  Refractory anemias :
There are less than 5% blasts found in the bone marrow.
This subtype of MDS does not often turn into
AML. Refractory anemia with ringed sideroblasts (RARS).
People with this subtype of MDS have anemia, similar to
those with RA, except more than 15% of the red blood cells
are sideroblasts.

5. Sideroblastic anemias
 Sideroblastic anemias are a rare heterogeneous group of
refractory anemias characterized by
 Presence of ring sideroblasts in the bone marrow aspirate.
 A dimorphic peripheral blood picture. Microcytic
hypochromic red cells in hereditary form and macrocytic in
the acquired forms of the disease mixed with
normochromic cells.
 Tiny iron-containing inclusions called as Pappenheimer
bodies in the red blood cells (stain positively by Prussian
blue staining).
 Increased serum iron concentration and markedly increased
storage iron.
 Ineffective erythropoiesis due to non-viable sideroblasts

6. Sideroblastic anemia
 Anemia is a disease in which the bone marrow produces ringed
sideroblasts rather than healthy RBCs (erythrocytes).
 Caused either by:-
 genetic disorder
 myelodysplastic syndrome,
 Can evolve into hematological malignancies
 (especially acute myelogenous leukemia).
 the body has iron available but cannot incorporate it
into hemoglobin, which RBCs need to transport oxygen efficiently.
 Sideroblasts are atypical, abnormal nucleated erythroblasts with
granules of iron accumulated in perinuclear mitochondria.
 Sideroblasts are seen in aspirates of bone marrow.
 Ring sideroblast are named because of the arrangement of the iron
granules in a ring form around the nucleus.

7. Morphology of sideroblasts
 Grouped on Morphology three types of sideroblasts:-
 Type 1 sideroblasts: fewer than 5 siderotic granules in
the cytoplasm
 Type 2 sideroblasts: 5 or more siderotic granules, but
not in a perinuclear distribution
 Type 3 or ring sideroblasts: 5 or more granules in a
perinuclear position, surrounding the nucleus or
encompassing at least one third of the nuclear
circumference.

8. Classification
 Sideroblastic anemia is typically divided into subtypes
based on its cause.
 Hereditary
 Congenital Sideroblastic anemia may be X-linked or
autosomal.

9. HEREDITARY SIDEROBLASTIC
ANEMIAS
 Hereditary sideroblastic anemias comprise a clinically,
genetically and hematologically heterogeneous group of
rare disorders.
 It may be inherited as X-linked or an autosomal
(dominant or recessive) disorder.
 patients generally have low levels of δ-aminolevulinic
acid synthase (ALAS) enzyme in the normoblasts leading
to defective synthesis of hemoglobin.

10. Clinical Features
 Sex: It predominantly affects males.
 Anemia: It may not manifest until adolescence.
 Iron overload may result in:
Hepatomegaly
Splenomegaly
Impaired growth and development
Cardiac arrhythmias

11. Symptoms
 Skin paleness,
 fatigue, dizziness,
 enlarged spleen and liver.
 Heart disease, liver damage,
 and kidney failure can result from iron buildup in these
organs.

12. Causes
 Drug-
induced: ethanol, isoniazid, chloramphenicol, cycloserin
e, Linezolid, oral contraceptives
 Nutritional: pyridoxine (Vitamin
B6) or copper deficiency
 Diseases: Rheumatoid arthritis or multiple myeloma
 Genetic: ALA synthase deficiency (X-linked, associated
with ALAS2)

13. Causes
 failure to completely form heme molecules in
the mitochondrion lead to
 deposits of iron in the mitochondria that form a ring
around the nucleus of the developing RBC.
 Sometimes the disorder represents a stage in evolution
of a generalized bone marrow disorder that may
ultimately terminate in acute leukemia.
 Toxins: lead, copper, or zinc poisoning

14. Laboratory Findings Peripheral Blood
 Red cell indices:
 MCV: Decreased
 MCH: Decreased •
 Peripheral smear RBCs: Red cells show dimorphic blood
picture with moderate degree of anisopoikilocytosis.
 There are microcytic hypochromic red cells mixed with
normocytic normochromic red cells. Few red cells may
show basophilic stippling. Occasional nucleated RBC may be
found.
 WBCs and platelets: Usually normal. However, leucopenia
and thrombocytopenia may develop due to hypersplenism.
 Reticulocyte count: 0.2-1%.

15. Diagnosis
 Ringed sideroblasts are seen in the bone marrow.
 The anemia is moderate to severe
 Dimorphic with
marked anisocytosis and poikilocytosis.Basophilic
stippling is marked and target cells are
common. Pappenheimer bodies are present.
 MCV is decreased (i.e., a microcytic anemia).
 RDW is increased with the red blood cell histogram
shifted to the left.

16. Bone Marrow
 Bone Marrow • Cellularity: Hypercellular •
Erythropoiesis: Erythroid hyperplasia but is ineffective.
The reaction may be normoblastic or
micronormoblastic.
 Iron: Moderate to marked increase in bone marrow
iron.
 Ring sideroblasts with partial/ complete perinuclear
ring of iron granules are characteristically present
 Other Findings • Serum ferritin, serum iron and
transferrin saturation are increased.

17. Diagnosis
 Leukocytes and platelets are normal.
 Bone marrow shows erythroid hyperplasia with a
maturation arrest.
 In excess of 40% of the developing erythrocytes are
ringed sideroblasts.
 Serum iron, percentage saturation and ferritin are
increased. The
 TIBC is normal to decreased.
 Stainable marrow hemosiderin is increased.

18. ACQUIRED IDIOPATHIC
SIDEROBLASTIC ANEMIA
 • The term primary or idiopathic is applied when other
causes of sideroblastic anemia cannot be identified. •
Acquired idiopathic sideroblastic anemia (AISA)
constitutes a subgroup of the myelodysplastic
syndromes refractory anemia with ring sideroblasts
(RARS). Majority present after 40 years of age.
 The dimorphic anemia has both hypochromic-
microcytic and macrocytic red blood cells, and the MCV
is usually high.
 At least 15% or more of erythroblasts (early and late
forms) in bone marrow are ring sideroblasts.

19. Secondary (drug- or toxin-
induced)
 Sideroblastic Anemia This form of sideroblastic anemia is secondary to various
agents that interfere with heme synthesis.
 Antituberculous drugs: Long-term therapy with isoniazid, cycloserine and
pyrazinamide.
 Lead poisoning: Lead interferes with heme synthesis by blocking the enzymes ALA
synthase, ALA dehydratase and heme synthetase. •
 Chloramphenicol: Sideroblastic anemia results probably due to inhibition of
mitochondrial protein synthesis.
 Copper deficiency or zinc overload: This results in sideroblastic anemia and
neutropenia.
 Copper chelators in large doses, such as penicillamine, can produce sideroblastic
anemia. •
 Ethanol-induced anemia: This is perhaps the most common of the reversible
sideroblastic anemias.
 Folate deficiency, hypomagnesemia and hypokalemia are concomitant findings. •
 Primary pyridoxine deficiency: It is often associated with malnutrition, is
occasionally associated with sideroblastic anemia.

20. Laboratory findings
 Increased ferritin levels
 Normal total iron-binding capacity
 Hematocrit of about 20-30%
 Serum Iron: High
 High transferrin saturation
 MCV is usually normal or low.
 With lead poisoning, see coarse basophilic stippling of RBCs
on peripheral blood smear
 Specific test: Prussian Blue stain of RBC in marrow. Shows
ringed sideroblasts.
 Can also cause microcytic hypochromic anemia.

21. CONGENITAL
DYSERYTHROPOIETIC ANEMIA
 (CDA) Congenital dyserythropoietic anemias (CDAs) are
characterized by ineffective erythropoiesis and marrow erythroid
multinuclearity. Three common types are recognized.
 Ring sideroblasts with partial perinuclear ring of iron granules
 CDA-I is characterized by macrocytic anemia. Bone marrow shows
megaloblastic erythropoiesis with internuclear chromatin bridges.
CDA-II is the most common form and presents with normocytic
normochromic anemia. Bone marrow shows normoblastic
hyperplasia with binuclear and multinuclear normoblasts.
 CDA-II is distinguished from the others because it has a positive
acidified serum test and a negative sucrose hemolysis test. It is
also known as hereditary erythroblastic multinuclearity with
positive acidified serum test (HEM-PAS).
 CDA-III has giant erythroid precursors, with more pronounced
multinuclearity (gigantoblasts) and a macrocytic anemia.
 In contrast to CDA-I and CDA-II, which are autosomal recessive,
CDA-III has autosomal dominant inheritance.

22. Treatment
 anemia is so severe that support with transfusion is
required.
 Patients usually do not respond to erythropoietin therapy.
 improved heme level by moderate to high doses of Vitamin
 Severe cases of SBA, bone marrow transplant with limited
information about the success rate.
 In the case of isoniazid-induced sideroblastic anemia, the
addition of B6 is sufficient to correct the anemia.
 Desferrioxamine is used to treat iron overload from
transfusions.
 Bone Marrow Transplant (BMT) is the last possible
treatment.