Anemia:- Part 9 – Sideroblastic Anemia, and Anemia Due To Chronic Diseases
Sample for Sideroblastic Anemia
- EDTA blood is needed.
- Bone marrow smear for iron stain.
Definition of sideroblastic anemia:
- Sideroblastic anemia indicates a group of disorders with the presentation of:
- Ineffective erythropoiesis.
- Increased serum and tissue iron.
- Increased number of ringed sideroblastic RBCs in the bone marrow aspirate (at least 20%).
- Sideroblasts are normoblasts with abnormal stainable iron in the cytoplasm that form a ring around the nucleus.
- Normoblast contains ferritin. These cells are absent in iron deficiency anemia and anemia due to chronic infection.
- Siderocytes are normal reticulocytes that contain iron in the form of ferritin or hemosiderin in the mitochondria. These cells have no diagnostic importance.
- These anemias are due to abnormalities of heme synthesis.
- To qualify the sideroblastic anemia, >15% of ringed sideroblasts are to be found in the following:
- Congenital (inherited):
- This includes sex-linked congenital sideroblastic anemia.
- Autosommal recessive sideroblastic anemia.
- Acquired (drug-induced):
- Primary or idiopathic.
- Drugs include isoniazid and chloramphenicol.
- This may be seen in malignancies or malabsorption.
- Primary or idiopathic.
Pathophysiology of sideroblastic anemia:
- The pathogenesis is incompletely understood.
- It is due to abnormalities of heme metabolism.
- Several investigators found enzyme deficiency, including the deficiency of ALA synthase and uroporphyrinogen decarboxylase in these patients.
- Irrespective of the etiology, there is an abnormal deposition of iron or siderotic granules in normoblast mitochondria. The mitochondria are present around the nucleus.
- The body has an adequate amount of iron, but it cannot incorporate into hemoglobin.
- The iron (Fe) enters the developing RBCs but accumulates in the normoblast’s perinuclear mitochondria in primary sideroblastic anemia.
Classification of sideroblastic anemia:
A. Inherited type:
- This is rare and is sex-linked.
- Sex-linked (X-linked) anemia is more common than Autosomal recessive sideroblastic anemia.
- The responsible gene is ALAS2, found on the sex chromosome X.
- Autosomal, pyridoxine-refractory.
- These sideroblastic anemias are usually present in childhood.
- MCV is usually low, and RDW is usually high.
B. Acquired type:
- Primary (idiopathic).
- Associated with myeloproliferative disorders like leukemia and polycythemia vera.
- Pyridoxine deficiency (responsive anemia):
- Drugs induced like INH, cycloserine, chloramphenicol, and chemotherapy.
- Vitamin B12 deficiency.
- Hemoglobin synthesis defects:
- Deficiency of vitamin B12 and folic acid.
- Erythropoietic porphyria.
- Lead poisoning.
- Other diseases are e.g., rheumatoid arthritis, carcinoma, megaloblastic, hemolytic anemia, hemolytic anemia, and malabsorption.
- A specially acquired rare form of Pearson syndrome has sideroblastic anemia, pancreatic insufficiency, and copper deficiency.
- Pyridoxine-responsive anemia:
- Classical type.
- Variant forms.
Signs and symptoms of sideroblastic anemia:
- Typically anemia appears early, usually within the first few months or years of life.
- The patients will show pallor and splenomegaly in the sideroblastic anemia.
Lab findings of sideroblastic anemia are:
- The diagnostic feature is nucleated RBCs with iron granules called ringed sideroblasts, present in the bone marrow and dimorphic picture in the peripheral blood smear.
- Hemoglobin is low.
- MCV is variable and may be low, normal, or increased.
- MCH and MCHC are often low but may be normal.
- White blood cells may show abnormality.
- RDW is increased.
- Serum iron is usually more than normal. There may be increased or normal iron stores.
- Ferritin level is also increased.
- Transferrin% saturation is high.
- The serum ferritin level is markedly raised.
- The serum B12 and folic acid levels are normal.
- Raised bilirubin level.
- LDH is raised.
- Decreased serum haptoglobin.
- Peripheral blood smears:
- It shows a dimorphic picture with the presence of normocytic (normal RBCs) and microcytic and hypochromic RBCs (small-size RBCs). Occasional macrocytes are seen.
- Microcytosis is more common in the inherited form of sideroblastic anemia.
- Peripheral blood smears show hypochromic anemia, which is microcytic, normochromic, or macrocytic (dimorphic picture).
- The dimorphic picture is seen in the primary type. It is prominent anisopoikilocytosis.
- The microcytic form is seen mostly in the inherited form of sideroblastic anemia. In comparison, the macrocytic form is seen in the acquired form.
- There may be seen iron-containing Papenheimer bodies, and may look like basophilic stippling.
- Bone marrow:
- It shows erythroid hyperplasia, but circulating reticulocytes are not increased (ineffective erythropoiesis).
- There are sideroblasts in the bone marrow aspirate. and these are >15%.
- Cytogenetics study shows a chromosomal anomaly in 25% to 50% of the cases.
- There are increased or normal iron stores.
Treatment of sideroblastic anemia:
- Treat the cause. Some patients respond when alcohol and drugs are stopped.
- In the primary type, these are unresponsive to various vitamins, especially pyridoxine (another reference says some patient responds to pyridoxine).
- Folic acid may be given in case of folate deficiency.
Anemia due to chronic diseases
Definition of anemia due to chronic diseases:
- This anemia occurs mostly in chronic inflammatory and malignant diseases.
- The anemia is present for several months following chronic diseases (which is present for several months).
- These are commonly associated with infections, malignant neoplasms, and autoimmune disorders.
- It is usually normocytic and either normocytic or hypochromic anemia.
Pathogenesis of anemia due to chronic diseases:
- The mechanism of this anemia is not clearly understood.
- The basic defect is in the iron utilization for erythropoiesis.
- It looks like there is a block of iron delivery from the reticuloendothelial system to RBCs.
- A chronic disease state blocks the transfer of stored iron to maturing erythroid precursors within the bone marrow.
- This will lead to iron deficiency in RBCs while the stores have abundant iron.
- There is a decreased release of iron from the macrophages to plasma.
- RBCs’ life span is reduced.
- Inadequate erythropoietin response to anemia is caused by the effect of cytokines like IL-1 and tumor necrosis factor (TNF) on erythropoiesis.
- Hepcidin, released by the liver in response to inflammation, will inhibit macrophages’ iron release and absorption.
- The anemia will respond to successful treatment of the cause but no response to iron therapy.
- Anemia due to chronic diseases may be due to:
- Decreased Erythropoietin response by the RBCs.
- Decreased RBCs survival.
- Defective iron absorption.
- Cytokines block the release of iron from the reticuloendothelial system for the development of RBCs.
Causes of anemia due to chronic diseases:
- This is seen in collagen diseases (autoimmune diseases).
- Systemic lupus erythematosus.
- Rheumatoid arthritis.
- Inflammatory chronic conditions.
- Chronic osteomyelitis.
- Fungal infection.
- Multiple myeloma.
Causes of anemia due to chronic diseases:
|Group of the anemia||Causes of the chronic diseases|
Signs and symptoms of anemia due to chronic diseases:
- Anemia appears for several months after the chronic disease.
- Anemia usually presents 1 to 3 months following the onset of chronic disease.
Lab findings of anemia due to chronic diseases:
- There is Low hemoglobin (7 to 11 g/dL).
- MCV is normal.
- RBCs may be normal or microcytic and hypochromic RBCs. This microcytosis is not as severe as iron deficiency anemia.
- Usually normocytic RBCs with normal MCV, rarely MCV is <75 fl.
- In some cases, we may see hypochromic or normochromic RBCs.
- Decreased Serum iron.
- TIBC is normal or decreased.
- The serum ferritin is normal or increased.
- There is a decreased % saturation.
- Normal to increased serum ferritin level.
- It needs to differentiate from iron deficiency anemia.
- Decreased sideroblastic cells (rare to absent ringed sideroblast).
Lab findings of the anemia due to chronic diseases:
|Lab test||Clinical parameters|
Table showing findings in various anemias:
|Type of anemia||Hb||MCV||MCH||MCHC|
Characteristic Findings in Various Anemias:
Iron binding capacity
|Iron deficiency||low||low <76 fl||low||low/normal||decreased||increased||decreased||increased|
|Megaloblastic||low||high >100 fl/cell||
|low 32 to 36 g/dL||raised/normal||increased|
|Chronic illness||low||low/normal||low||low||normal/ increased||normal / decreased||decreased||normal|
|Alpha Thalassemia||low or normal||low||low||low||normal /increased||normal||
Classification of anemia based on RDW:
|Cell size||Normal RDW||High RDW|
Abnormalities of RBCs morphology and their etiology:
Summary of lab findings in various anemias:
|Lab test||Iron-deficiency anemia||Pernicious anemia||Folic acid deficiency||Aplastic anemia||Thalassemia||Sideroblastic anemia||Hemolytic anemia||Post hemorrhagic anemia||Anemia of chronic diseases|
|Hemoglobin||Low||Low||Low||Low or normal||Low||Low||Low||Normal or low||Low|
|Hematocrit||Low||Low||Low||Low or normal||Low||Low||Low||Normal or low||Low|
|MCV||Low||High||High||A normal or mild increase||Low||Low||Normal or high||Slightly low||Low or normal|
|Reticulocytes count||A normal or mild increase||Low||Low||Low||Increased||A normal or mild increase||High||Increased||Normal|
|Plasma Iron||Low||Increased||Increased||Increased||Increased or normal||Increased||Normal or high||Normal||Low|
|Ferritin level||Low||Increased||Increased||Normal||Increased or normal||Increased||Normal||Normal||Normal|
|Serum B12 level||Normal||Low||Normal||Normal||Normal||Normal||Normal||Normal||Normal|
|Transferrin||Low||Mild increase||Mild increase||Normal||Increased||Normal||Normal||Mildly low|