This document discusses sideroblastic anemia, which is caused by an abnormal accumulation of iron in the mitochondria of red blood cell precursors called ring sideroblasts. There are several types of sideroblastic anemia, including hereditary forms caused by genetic mutations and acquired forms caused by drugs, toxins, or diseases. The condition is characterized by ring sideroblasts seen on bone marrow biopsy along with ineffective red blood cell production and iron overload. Treatment depends on the underlying cause but may include blood transfusions, vitamin supplements, iron chelation therapy, or bone marrow transplant in severe cases.
Aplastic anemia is one of the stem cell disorder which leads to pancytopenia in the peripheral blood and decrease production of all cell line in bone marrow. it require bone marrow transplantation to cure the patient.
causes of macrocytic anemia pathopysiology, sign and symptoms and the difference between macrocytic anemia megaloblastIc anemia. causes of hypersegmented neutrophils and its association between them. investigation and medical management plus pictures illustration.
Aplastic anemia is one of the stem cell disorder which leads to pancytopenia in the peripheral blood and decrease production of all cell line in bone marrow. it require bone marrow transplantation to cure the patient.
causes of macrocytic anemia pathopysiology, sign and symptoms and the difference between macrocytic anemia megaloblastIc anemia. causes of hypersegmented neutrophils and its association between them. investigation and medical management plus pictures illustration.
This presentation is focused on diagnostic utility of Red blood cell indices which will be very useful for undergraduate and postgraduate of medical field.
Hereditary spherocytosis is an inherited condition related to RBC destruction. its diagnosis is require to differentiate immune hemolytic anemia and G-6-P-D deficiency anemia
Megaloblastic anaemia is a red blood cell disorder due to the inhibition of DNA synthesis during erythropioesis.
Mitotically, the inhibition of the DNA synthesis impaires the progression of the cell cycle development from G2 to (M) stage.
Autoimmune hemolytic anemia (or autoimmune haemolytic anaemia; AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to insufficient plasma concentration.
presented by HAFIZ M WASEEM
university of education LAHORE Pakistan
i am from mailsi vehari and studied in lahore
bsc in science college multan
msc from lahore
This presentation is focused on diagnostic utility of Red blood cell indices which will be very useful for undergraduate and postgraduate of medical field.
Hereditary spherocytosis is an inherited condition related to RBC destruction. its diagnosis is require to differentiate immune hemolytic anemia and G-6-P-D deficiency anemia
Megaloblastic anaemia is a red blood cell disorder due to the inhibition of DNA synthesis during erythropioesis.
Mitotically, the inhibition of the DNA synthesis impaires the progression of the cell cycle development from G2 to (M) stage.
Autoimmune hemolytic anemia (or autoimmune haemolytic anaemia; AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to insufficient plasma concentration.
presented by HAFIZ M WASEEM
university of education LAHORE Pakistan
i am from mailsi vehari and studied in lahore
bsc in science college multan
msc from lahore
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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.