Anemia – Part 2 – Iron Deficiency Anemia, Microcytic and hypochromic anemia

Sample

1. Take the blood in the EDTA.
2. Make fresh peripheral blood smear.
3. For iron, draw the first-morning blood sample because of the diurnal variation.

Definition

1. Iron deficiency anemia is the most common cause of anemia, and iron is the most common dietary deficiency globally.
2. Iron deficiency results in decreased quantity defect in hemoglobin production, which leads to small, pale microcytic, and hypochromic RBCs.
3. DNA synthesis is normal.
4. Iron-deficiency anemias are divided into three groups:
   1. Iron metabolism where there is iron deficiency.
   2. Disorders of heme synthesis seen in sideroblastic anemia.
   3. Disorder of globin protein synthesis seen in Thalassemia.

The anemia is caused by:

1. Inadequate intake of iron:
   1. Meat, eggs, and green leafy vegetables are a good source of iron.
   2. Pregnant ladies and children need a more iron-rich diet.
   3. Pregnancy or increased blood loss in menstruation leads to iron deficiency.
2. Internal bleeding in stomach ulcers and polyps of GIT.
   1. Too much use of aspirin may cause internal bleeding.
   2. Esophageal varices.
   3. In the case of partial gastrectomy.
   4. Carcinoma of the stomach, caecum, colon, or rectum.
   5. Bleeding from the hemorrhoids.
   6. Rarely hematuria, hemoglobinuria, and self-inflicted blood loss.
3. Parasitic infestation by the hookworm.
4. Malabsorption like Gluten-induced enteropathy and gastrectomy.
   1. Inability to absorb iron from GIT like in bypass surgery of stomach or intestine and Celiac disease.
   2. In the case of gastric, duodenal, or jejunal resection.
5. People at risk of developing iron deficiency are:
   1. Ladies of childbearing age period.
   2. People with a poor diet.
   3. People who frequently donate blood or professional donors.
   4. Vegetarian who does not eat meat or iron-rich foods.
   5. Infants or children who are mainly in milk and do not take solid foods.
   6. Poor diet in poor people.
6. Pregnancy and lactation, where more iron is needed. In pregnancy, iron needs maybe around 1000 mg.  There is an increased maternal red cell mass of roughly 35%. There is the diversion of the iron to the fetus.
   1. There is 300 mg of iron transfer to the fetus.
   2. There is blood loss during the delivery.
   3. Iron supplement needed if the Hb is below 10 g/dL or MCV is <82 fL in the third trimester.

Causes of iron deficiency anemia:

Infants/adults	Causes
Infants	Decreased intake of iron Parasitic infestation Infants on an only milk diet and no solids intake
Adults	Decreased intake Strict vegetarians Blood loss in menses and colon cancers Pregnancy Lactation Decreased absorption in celiac disease, small intestine resection

1. Stages of iron deficiency:
   1. Decreased Iron stores: Iron stores are depleted. There is decreased serum ferritin.
   2. Defective hemoglobin synthesis: There is a deficiency of iron, which will lead to defective hemoglobin synthesis.
      1. There will be decreased serum iron.
      2. There is decreased transferrin saturation.
      3. There is an increased RBC protoporphyrin.
      4. There is an increased total iron-binding capacity (TIBC);
      5. The patient will be anemic.
   3.  Development of anemia: There will be hypochromic and microcytic anemia. The patient will show:
      1. Low Hb.
      2. Decreased Hct.
      3. Decreased RBC count.
      4. Decreased MCV.
      5. It is increased serum soluble-transferrin receptors.

Pathophysiology

1. Iron is one of the most important components of hemoglobin.
   1. Decreased iron in hemoglobin leads to anemia.
   2. Hemoglobin contains roughly 37% of the iron by weight.
2. The iron is taken as ferric form, and it changes to the ferrous form in the stomach by the  Hydrochloric acid.
3. It is then absorbed mainly in the small intestine.
   

   Iron metabolism

1. 1. The leftover is excreted in the feces.
   2. The body uses 1 mg per day of iron, and there is the storage of iron 1000 mg.
   3. It then combines with the apoferritin with the protein and makes a complex of ferritin.
   4. Iron is stored as ferritin in the body.

3. Now Ferric ions combine with the Transferrin, which is synthesized in the liver.
4. Transferrin helps:
   1. Make an iron insoluble form.
   2. It prevents iron-mediated free radical toxicity.
   3. This facilitates iron transport into the cells.
      

      Iron cycle and storage

5.  Iron is stored as ferritin in hepatocytes, macrophagic cells (bone marrow), RBCs, and the muscles.
   1. Ferritin release iron for the formation of hemoglobin and heme protein.
      

      Iron Storage in the Body

Signs and symptoms of Iron deficiency anemia are:

1. Iron deficiency anemia is more common in children, young females, and older people.
   1. There is an increased need for infants, children, and pregnant women.
   2. In females, iron deficiency occurs due to menstrual cycles.
   3. Chronic loss of blood from the GI tract is the usual reason for iron deficiency.
2. There are general fatigue and weakness.
3. Skin is pale, and also conjunctiva will be pale.
4. The patient may feel dizziness.
5. These patients, particularly children, have a craving to eat dirt, ice, or clay. Sometimes these children lick the walls.
6. There may be a feeling of tingling or crawling in the legs.
7. Patients have cold hands and feet.
8. These patients may have tachycardia, as fast or irregular heartbeat.
9. Sometimes have a headache.
10. Nails are brittle.
11. The tongue has soreness or swelling.
12. There is a case report of renal cell carcinoma with microcytosis and normochromic anemia.

Complications of Iron deficiency anemia are:

1. There is tachycardia and may lead to heart failure and an enlarged heart.
2. In pregnancy, there may be premature birth and low weight of the baby.
3. Children and infants may have delayed and developmental abnormalities.
   

   Iron deficiency anemia complications

Iron deficiency anemia lab findings:

1. Decreased serum ferritin is the early sign and followed by a decrease in the % saturation of transferrin, decreased serum iron, and increased zinc protoporphyrin (ZPP).
   1. Later on, hemoglobin will fall.
2. MCV is reduced to 50 to 60 fl (where the normal value is 77 to 93 fl).
3. MCH is reduced to 15 to 20 pg (where the normal value is 27 to 32 pg).
4. MCHC is reduced to 20 to 25 g/dl (where the normal value is 31 to 35 g/dl).
5. The serum iron level is decreased (very low).   Normal serum iron is 50 to 150 µg/dL.
6. The serum ferritin level is low <10 ng/dL.
7. Raised total iron-binding capacity (TIBC). Normal TIBC is 250 to 450 µg/dL.
8. Percent transferrin saturation normal value is 20% to 50%, and normally transferrin 33% saturated.
   

   The formula for Transferrin % saturation

9. RBC protoporphyrins increased.
10. The peripheral blood smear shows anisocytosis, poikilocytosis with the presence of target cells.
    1. There are microcytic, hypochromic red blood cells.
       

       Microcytic and hypochromic anemia

       

       Microcytic and hypochromic anemia

11. There may be leucopenia.
12. The serum transferrin receptor is raised.
13. Platelets count high.
14. RDW is high.
15. Bone Marrow shows erythroid hyperplasia, and this is polychromatic.
    1. Micro-normoblasts are seen.
       1. The cytoplasm is decreased and sometimes shows the only rim.
       2. Nuclei may be pyknotic.
       3. Erythroblast iron is absent.
    2. Myeloid series is usually normal, and M: E ratio is reduced.
    3. Megakaryocytes are normal in number and morphology.
16. The iron stain of bone marrow shows the absence of stainable iron in the reticulum cells, and normoblast looks like sideroblasts. This is a more reliable test by Prussian blue reaction.
    

    Causes of Iron Deficiency Anemia

Lab findings in iron deficiency anemia:

• Test	Result
  Hemoglobin	Normal or low
  MCH	Decreased
  MCV	Decreased <80 fl
  MCHC	Decreased
  RDW	Increased
  Reticulocytes	Decreased
  Total iron	Decreased (normal =50 to 150 µg/dL)
  TIBC	Increased (normal = 250 to 450 µg/dL)
  Ferritin	Decreased (normal = 20 to 250 ng/mL)
  Transferrin receptor	Increased
  % transferrin saturation	Decreased (normal 20% to 50%)
  Platelet count	High
  WBC	Leucopenia
  Bone marrow iron store	Decreased or absent
  Erythroblast iron	Absent
  Free RBC protoporphyrin	Increased

FEP = Free erythrocytes protoporphyrin.

TIBC = Total iron-binding capacity.

RDW = Red cell distribution width.

---