Anemia definition and types.

 ANEMIA

Anemia is defined as a reduction in hemoglobin concentration below the level, which is expected for healthy persons of the same age and Sex, and in the same environment. Adequate oxygen cannot be delivered to various organs and tissue due to bid. the oxygen-carrying capacity of the blood. Anemia may occur without symptoms and may be detected incidentally during a medical examination. When severe enough, clinical features due to anemia result from hypoxia such as fatigue, weakness, dizziness, fainting, and mental confusion. Pallor of skin, mucous membranes, and conjunctiva is present.

 

Classification of Anemia

There are two ways of classifying anemia.

• Etiological classification.

• Morphological classification.

 

• Etiological Classification •

→Nutritional deficiencies- "Anemia due to decreased production of RBC.

1.   Iron Deficiency Anemia:

Iron deficiency is the most common cause of anemia, Pregnant women, women in the reproductive age group, and children under 5 years of age. particularly susceptible to nutritional deficiency. In men and postmenopausal women, blood loss is the main cause.

Causes of Iron deficiency anemia -

• Nutritional deficiency due to poor. diet ton increased requirements: infants and children, women in reproductive age group, pregnancy.

• Blood loss: Esophageal varices, peptic ulcer, carcinoma of the stomach, hook warm infestation, Menorrhagia, Hematuria.

• Malabsorption: Celiac disease.

• Laboratory Features –

a.       Low hemoglobin and low packed cell volume.

b.      Low MCV (<80μl), low MCH (<27pg/C), low MCHC (<30 gm/dl)

c.       Blood smear shows microcytic, hypochromic RBC and pencil cells and low reticulocyte count.

d.      Serum ferritin is less than 15 μg/dl.

e.       Low serum iron – (< 30 μg/dl), low Total Iron Binding Capacity (TIBC) – (> 400 μg/dl), Transpherin saturation is less than – 10%.

f.        Increased Soluble transferrin receptor (sTfR) in serum.

g.       Bone marrow iron stain: This is the gold standard for diagnosis of iron deficiency and shows a lack of stainable iron in the bone marrow.

 

2.   Megaloblastic Anemia:

Megaloblastic anemia results from deficiency of either folate or vitamin B12. Folate and vitamin B12 are essential for the synthesis of deoxyribonucleic acid (DNA) in case of deficiency, therefore, there is a defective synthesis of DNA in all the proliferating cells including bone marrow cells, Vitamin B12 is also required for neurological functions. Anemia, mild jaundice, and glossitis, are common to both folate and vitamin B12 deficiency.

 

• Causes- Megaloblastic anemia is most often due to Hypovitaminosis, specifically vitamin B12 (cobalamin) and folate deficiencies.

•Laboratory Features –

a.       Macrocytic anemia → MCV > 100 fl in adults. An elevation of I means cell volume is an early sign of anemia.

b.      Blood smear shows oval macrocytosis, basophilic stippling, Howell-Jolly bodies, and hypersegmentation of neutrophils, (>5% of neutrophils showing 5 or more lobes - Right shift).

c.       Reticulocyte count is normal on low.

d.      Bone marrow shows megaloblasts, erythroid hyperplasia, and giant meta myelocytes and bands.

e.       Low, Vitamin B12, serum folate, and Red Cell folate.

 

3.   Anemia of Chronic Disease:

The three disease categories are associated with anemia of chronic infection, inflammation, and malignancy. There is a block in the release of storage iron from macrophages for erythropoiesis that is mediated by inflammatory cytokines.

• Disease associated with this –

*Chronic infections: Tuberculosis, urinary tract infection, bronchiectasis, osteomyelitis, subacute bacterial endocarditis.

*Chronic inflammation: Rheumatoid arthritis, Systemic lupus erythematosus.

*Malignancy

• Laboratory Features –

a.       Normocytic normochromic anemia (70% Cases) or Microcytic hypochromic anemia (30%).

b.      Decreased serum iron decreased total iron binding capacity, and normal or raised serum ferritin. Serum transferrin receptor level is normal.

c.       Increased marrow storage iron.

d.      Erythrocyte sedimentation rate is increased out of proportion to the degree of anemia.

 

4.   Sideroblastic Anemia:

In sideroblastic anemia, heme synthesis is deficient. A mitochondrial defect leads to the failure of incorporation of iron into heme. Iron accumulates in mitochondria that surround the nucleus of erythroblasts forming ringed sideroblasts.

• Causes –

*Dimorphic anemia: Blood smear shows the dual population of cells- Normocytic normochromic and microcytic hypochromic.

*Ring sideroblasts in bone marrow.

• laboratory Features –

a.       Microcytic hypochromic anemia.

b.      Normal to low reticulocyte count.

c.       Increased ferritin levels.

d.      Decreased total iron-binding capacity.

e.       Hematocrit 20% - 30%

f.        High serum iron.

g.       Basophilic stippling of red blood cells on peripheral blood smear in lead poisoning.

h.      Prussian blue stain of RBC in the marrow, shows ringed sideroblasts.

i.        Thrombocytopenia and leukopenia.

 

5.   Aplastic anemia:

Aplastic anemia is characterized by pancytopenia in peripheral blood and decreased cellularity in the bone marrow. It can occur at any age.

• Causes –

*Drugs: Antibacterial, nonsteroidal anti-inflammatory drugs, antithyroid drugs, cytotoxic drugs.

*Infections: Hepatitis, Epstein Barr virus, Mycobacteria.

*Systemic lupus erythematosus.

Laboratory Features –

a.       In CBC – Demonstrate pancytopenia, Low hemoglobin, and low reticulocyte count.

b.      Bone marrow examination to demonstrate depletion of hematopoietic precursors and hypoes plurality.

→Anemia due to increased destruction of RBC for Hemoglobin –

1.   Thalassemia:

Thalassemia is an inherited disorder characterized by the reduced or absent synthesis of Alpha or Beta globin polypeptide chains.

*Classification -- A. α–Thalassemia. and B. β–Thalassemia.

A. α–Thalassemia:

Normally, there are four alpha globin genes, two on each member of chromosome 16. Alpha thalassemia usually results from gene deletions of the α gene from chromosome 16.

> There are 4 conditions –

        I.            Deletion of one alpha gene from one pair of chromosome-16 (_ α/α α) → α–Thalassemia in carrier state (no syndrome)

      II.            Deletion of one alpha gene from each pair of chromosome-16 (_ α/_ α) or deletion of two genes from one pair of chromosome-16 (­_ _/α α) → Mild Hypochromic anemia (no syndrome)

   III.            Deletion of 3 alpha gene from two pairs of chromosome-16 (_ _/_ α) → Hb H disease –

Lab Features –

a.       Low Hemoglobin (7-10 gm/dl)

b.      Jaundice and hepatosplenomegaly.

c.       Microcytic hypochromic RBC and Hb H inclusion RBC.

d.      Variable amount of Hb H electrophoresis.

   IV.            Deletion of 4 alpha genes (_ _/_ _) → Hb Bart’s hydrops fetalis syndrome.

Lab Features –

a.       Pale generalized edema resulting from prolonged intra-uterine anemia,

b.      Hepatosplenomegaly

c.       Congenital abnormalities including cardiovascular, skeletal, and urogenital systems,

d.      Enlargement of the placenta.

B. β–Thalassemia:

Normally, there are two beta-globin genes, one each member of chromosome 11 beta-thalassemia results from a single base substitution (point mutation) in the beta-globin gene. More than 150 mutations of the beta-globin gene have been reported to cause β–Thalassemia.

·       There are two major forms of β–Thalassemia –

*β⁰ – Thalassemia – Characterized by the absence of beta-chain synthesis.

* β⁺ – Thalassemia – Beta-chain synthesis is reduced.

§  β – Thalassemia Major (Homozygous): β-thalassemia major results when both the beta-globin genes are defective, genotype β⁰/ β⁰ or β⁰/ β⁺. It is characterized by severe anemia and requires regular blood transfusion therapy for survival.

Laboratory Features –

a.       Severe anemia – (hemoglobin < 7.0 gm/dl)

b.      Blood smear shows marked variation in size and shape of red cells, red cell fragments, hypochromic, target cells, basophilic stippling, and nucleated RBCs.

c.       Reticulocytosis (5-15%)

d.      Low MCV, MCH, and MCHC.

e.       Markedly elevated Hb-F on electrophoresis.

 

§  β – Thalassemia Intermedia: This results from homozygous inheritance of mild β⁺ Thalassemia (genotype β⁺/ β⁺). It is characterized by a moderate degree of anemia which does not require regular blood transfusion therapy. Worsening of anemia occurs during infections and pregnancy.

Thalassemia intermedia presents at a later age (2-5 years) than thalassemia major. These patients have chronic hemolytic anemia, splenomegaly, and skeletal changes.

       Laboratory Features –

a.       Moderate degree of anemia (hemoglobin 7-10 gm/dl)

b.      Blood smear shows less severe abnormalities than thalassemia major.

c.       Reticulocytosis (5-10%)

d.      Variable elevation of hemoglobin F on electrophoresis.

 

§  β – Thalassemia Minor (Heterozygous): Usually individuals have one abnormal beta-globin gene. (β⁰/ β or β/ β⁺)

Laboratory Features –

a.       Hemoglobin slightly low or normal (> 10 gm/dl)

b.      Low MCV and MCH, MCHC.

c.       Blood smear shows microcytic hypochromic RBC, target cells.

d.      Normal serum ferritin.

e.       Hb-electrophoresis shows elevated Hb-A₂ (> 3.5)

 

2.   Sickle cell Disease:

It is an inherited group of disorders; Red Blood Cells convert into a sickle shape. The cells die early, leaving a shortage of healthy red blood cells (sickle cell anemia), and can block blood flow causing pain (sickle cell crisis).

A person has sickle cell trait when the Hb-S gene is inherited from any one parent and a normal Hb gene – Hb A is inherited from the other. They are a carrier of the Hb-S gene.

That means they can pass it on when they have a child. If the child’s other parent also has sickle cell trait or another faulty Hb gene that child has a chance of having Sickle Cell Disease.

A.      (Hb-A/Hb-A) – Normal, B. (Hb-A/Hb-S) – Sickle Cell Trait C. ( Hb-S/Hb-S) – Sickle Cell Anemia.

Laboratory Features –

a.       Anemia Conditions.

b.      High Reticulocyte Count (> 1.5%)

c.       Target Cells and Howell-Jolly bodies on peripheral blood smear.

d.      Abnormal hemoglobin forms on hemoglobin electrophoresis – Hb-S and Hb-Sc.

 

·     Morphological Classification •

 

1.   Hypochromic Microcytic Anemia:

 

A.      Iron-deficiency Anemia.

B.      Thalassemia α and β.

C.      Sideroblastic Anemia.

D.     Chronic Disease.

• Laboratory Features –

1.      Low MCV – RBC size < 70 fl

2.      Infection, Cancer, Inflammation

3.      Lead Toxicity, Hb-F trait, Copper deficiency

4.      In born errors of iron metabolism.

 

2.   Macrocytic Anemia:

 

A.      Aplastic Anemia

B.      Megaloblastic Anemia

C.      Liver Disease

D.     Obstructive Jaundice

• Laboratory Features –

1.      High MCV – RBCs Size > 85 fl

2.      Increased Erythropoiesis.

3.      Syndromes with elevated Hb-F.

4.      Paroxysmal nocturnal hemoglobinumia.