Anemia

What sample is needed for an Anemia workup?

1. EDTA blood is needed.
2. For RBC morphology, a direct smear is preferred.`
3. Bone marrow is also advised.
4. Also, a bone biopsy may be needed.

How will you define Anemia?

1. Anemia is a decrease in hemoglobin concentration depending on the patient’s age and sex.
   1. The diagnostic criteria are low hemoglobin, hematocrit (Hct), or decreased RBC count.

What are the criteria for anemia?

1. Hemoglobin:
   1. Male = Hb <13.5 g/dL.
   2. Female = Hb 11.5 g/dL.
   3. 2 years to puberty = 11.0 g/dL.
   4. A Newborn = 14.0 g/dL is a lower limit because of the high Hb.
2. Hematocrit (Hct)
   1. Male = <42%.
   2. Female = <37%.
3. In a broad sense, anemia is the inability of the blood to supply adequate O2 to the tissues for proper metabolism.
4. These are the most common hematological disorders.
5. Diagnosis is essential for the physician in treating the cause of anemia.

What are the factors for effective erythropoiesis?

1. Level of iron and cobalt.
2. Vitamin B12.
3. Vitamin B6.
4. Riboflavin.
5. Thiamine.
6. Vitamin C.
7. Vitamin E.
8. Hormones like:
   1. Androgens.
   2. Thyroxine.

What are the types of Hemoglobin?

• To understand the anemias, it is better to know the hemoglobin types and structure:

Hb F structure

What is the role of hemoglobin in O2 transport (Hb/O2 dissociation curve)?

1. The RBCs carry O2 from the lungs to the tissues and bring CO2 in the venous blood to the lungs.
2. This is dependent upon the 2,3-diphosphoglycerate (2,3-DPG).
3. When O2 is unloaded, the β-chain of Hb pulls apart, permitting the entry of the metabolite 2,3-DPG, which results in a lower molecular affinity for O2.

4. O2 saturation is an indicator of the % of Hb saturated with O2.
5. When 92% to 100% of the Hb carries O2, the tissues adequately provide the O2 supply, which means normal O2 dissociation.
6. Normally, O2 exchange takes place:
   1. 95% saturated arterial blood with a mean arterial O2 tension of 95 mmHg.
   2. 70% saturated venous blood with a mean venous O2 tension of 40 mmHg.
   3. The curve’s normal position depends upon the concentration of 2,3-DPG, H+ ions, and CO2 in the RBCs and the structure of the Hb molecule.

What are the functions of Hemoglobin?

1. RBCs in arterial blood carry O2 from the lungs to the tissues and take back CO2 in the venous blood.

2. The main function is with the help of hemoglobin (Hb) molecules, as the Hb molecule loads and unloads the O2.
3. α1β1 and α2β2 globin stabilize the molecule.

How will you classify Anemia?

Anemia may be classified roughly based on Hb level:

1. Severe anemia when the Hb is <7 g/dL.
2. Moderate when the Hb is  7 to 10 g/dL. This group will not produce evident S/S. in most cases.

How will you classify Anemia based on RBC morphology?

1. Normochromic and normocytic anemias are due to:
   1. Anemia of acute hemorrhage.
   2. Hemolytic anemia.
   3. Anemia due to chronic diseases.
2. Hypochromic and microcytic anemias are due to:
   1. Iron deficiency anemia.
   2. Thalassemia.
3. Normochromic and macrocytic anemias are due to:
   1. Vit. B12 deficiency.
   2. Folate deficiency.
      1. Normochromic and macrocytic anemia is a late vitamin B12 and folate deficiency.

How will you classify anemia based on physiologic abnormality?

1. Defective maturation of erythropoiesis.
2. Hemolytic anemia is where the increased breakdown of the RBCs occurs.
   1. The defect is due to increased RBC precursors compared to the degree of anemia.

How will you classify the anemia based on etiology?

1. Increased RBC destruction due to intra or extra-red blood cell defects.
2. Increased blood loss, which may be acute or chronic.
3. Defective RBC formation due to a lack of factors necessary for erythropoiesis.

How will you classify Anemia based on the category?

1. Increased destruction of the RBCs
   1. Hemolytic anemia (nonimmune).
   2. Immune hemolytic anemia.
2. Anemia due to blood loss in hemorrhage.
3. Nutritional deficiency, such as folate or vitamin B12 deficiency.
4. Toxicity due to drugs.
5. Infections.
6. Infiltration of the bone marrow by the cancer cells.
7. Hereditary or acquired defect in the RBCs.
8. Hematopoietic stem cell arrest or damage.
9. Idiopathic or unknown cause.

What are the types of Anemias based on MCV?

Anemia is divided based on RBC indices (MCV) into the following broad categories:

1. Microcytic, MCV <80 fl.
2. Normocytic, MCV 80 to 100 fl.
3. Macrocytic, MCV >100 fl.

How will you classify the anemia based on RBC indices?

1. Normocytic:
   1. MCV is 80 to 100 fl (femtoliter).
   2. MCHC = 32 to 36%
2. Macrocytic:
   1. MCV = >100 fl.
3. Microcytic and hypochromic:
   1. MCV = <80 fl.
   2. MCHC = <32%.

How will you classify anemia?

What are the findings in various anemias?

What are the Laboratory Criteria for the Diagnosis of Anemias?

1. Hemoglobin is less than 12 to 13 G/dL.
2. Hematocrit is less than 36 to 41%.
3. Reticulocyte count was normal at 0.5 to 1.5%.
4. MCV is a better choice for classifying anemias and their differentiation. This is useful for the screening of occult alcoholism.
5. If MCV is high, then advise:
   1. Reticulocyte count.
   2. Vit.B12.
   3. Folate level.
6. If MCV is low, then advise:
   1. Serum Iron.
   2. Iron binding capacity (TIBC).
   3. If the above two tests are low, advise Ferritin and Bone marrow examination.
   4. If normal, then advise electrophoresis.
7. If MCV is normal, then advise:
   1. Serum Iron.
   2. Iron Binding Capacity. (TIBC).
   3. Comb’s test.
   4. Peripheral blood for RBC morphology.

How will you do the routine workup of the patient with anemia?

1. The patient’s detailed clinical history for diagnosis, physical examination, signs, and symptoms, with the following lab workup.
2. Hemoglobin and hematocrit.
3. Red blood cell count.
4. Blood indices:
5. MCH:
   1. It has limited value in the differential diagnosis of anemias. This is instrumental calibration.
6. MCHC:
   1. It is also instrumental in calibration, and changes occur very late in iron-deficiency anemia when it is very severe.
   2. This is better for evaluating hypochromasia than MCH.
7. Red cell distribution width (RDW):
   1. It helps to classify anemia with the help of MCV.
   2. RDW is more sensitive to the differentiation of microcytic anemia than macrocytic RBCs.
   3. This has no value in patients without anemia.
8. Serum iron:
   1. Normal = 50 to 150 µg/dL).
   2. Total iron serum helps diagnose anemia.
   3. It differentiates between hemochromatosis and hemosiderosis.
   4. It should be measured along with TIBC to evaluate iron deficiency.
   5. This also helps to evaluate acute iron toxicity in children.
9. Total iron-binding capacity (TIBC):
   1. Normal = 250 to 450 µg/dL).
   2. It helps in the differential diagnosis of anemias.
   3. It should be done along with serum iron to evaluate the % saturation and diagnose iron deficiency anemia.
10. Transferrin:
    1. Serum Transferrin level is needed for the D/D of anemia.
11. Percent transferrin saturation:
    1. Normal % transferrin saturation = 20% to 50%.
    2. Calculation of the % transferrin saturation =
       1. Serum iron ÷ TIBC x 100 
       2. Transferrin is usually 33% saturated.
    3. This is used for the D/D of the anemias.
    4. This helps in the screening of hereditary spherocytosis.
12. Ferritin:
    1. Serum ferritin (normal = 20 to 250 ng/dL).
    2. It correlates with the total body iron stores.
    3. It differentiates between iron deficiency and excess.
    4. It correlates with total body iron stores.
    5. It will predict and monitor iron deficiency.
    6. It will give an idea about the effectiveness of iron-deficiency anemia treatment.
    7. It differentiates iron deficiency from chronic diseases.
    8. It monitors the iron status in patients with chronic kidney disease with or without dialysis.
    9. It is used to study the population’s iron level and response to iron supplements.
    10. It can detect iron overload and monitor iron accumulation.
    11. It can help guide the response to iron depletion therapy.
13. Peripheral blood smear:
    1. This will inform the abnormality of the RBC shape, size, and any inclusions.
    2. There is a dimorphic picture in a mixed deficiency of iron, vitamin B12, or folate; there are microcytes and macrocytes. In this case, blood indices may be normal.
    3. Also, find the abnormal white cells and assess the platelets.
    4. It can find blast cells like normoblasts or granulocyte blast cells.
14. Reticulocyte count:
    
    1. The normal range is 0.5 to 2.5%, and the absolute count is 25 to 125 x 10⁹/L.
    2. Reticulocytes are raised in anemia because of the raised level of erythropoietin.
    3. After the acute hemorrhage:
       1. Erythropoietin level rises in 6 hours.
       2. Reticulocyte level increases in 2 to 3 days, and the peak level reaches 6 to 10 days.
       3. Reticulocytes will be raised until the Hb becomes normal.
    4. If the reticulocyte count is not raised in anemia, it means a bone marrow abnormality or a lack of erythropoietin stimulus.
15. White blood cell count and platelet count:
    1. This will rule out the pancytopenia from the anemia.
       
    2. In hemolysis or hemorrhage, the neutrophils and the platelets are raised.
    3. In leukemias, the white cells are also raised.
16. Bone marrow examination:
    1. Bone marrow may be aspirated, or a biopsy may be taken.
    2. This will give the cellularity like myeloid: erythroid ratio, and the presence of abnormal cells, like cancer cells, that infiltrate.
    3. Can do Special stains like iron.

What are the normal adult blood indices values?

How would you describe Normochromic and normocytic Anemia?

Lab findings:

1. Low hemoglobin.
2. Normal MCV 80 to 95 fL.
3. Normal MCH ≥27 pg.
4. Normal MCHC.
   1. Mostly, these are due to acute blood loss.

• The peripheral blood smear shows normal-looking RBCs and normal RBC indices.

1. 1. The RBCs produced by the bone marrow are normal, but the number of RBCs in circulation is reduced for many reasons.

What are the causes of normochromic and normocytic anemia?

1. Iron deficiency in the early stages.
2. Acute blood loss.
3. Chronic diseases of the kidneys and the liver.
4. Infiltration by leukemia and multiple myeloma.
5. Drugs like chloramphenicol cause aplastic anemia.
6. Acquired hemolytic anemia may be from the prosthetic surgery of the heart.
7. Pregnancy is due to increased plasma volume.
8. Overhydration.

How would you describe microcytic and hypochromic anemia?

1. These are the most common types of anemia, and iron deficiency is the most common cause.

What are the causes of microcytic hypochromic anemia?

1. This is due to iron deficiency caused by decreased iron intake in the diet or impaired absorption.
2. Iron deficiency anemia.
3. Lead poisoning.
4. Thalassemia.
5. There may be an increased iron loss due to chronic bleeding.
6. There may be an abnormality in iron metabolism.
7. Increased demand by the body in:
   1. Infancy.
   2. Pregnancy.
   3. Lactation.
8. Due to cancer.
9. Hemorrhoids.
10. Hookworms.
11. Drugs like salicylates (aspirin).

How will you diagnose microcytic hypochromic anemia?

1. Low hemoglobin, males <12 g/dL and females <10 g/dL.
2. Low MCV <80 fL.
3. MCH < 27 pg.
4. Findings in the iron-deficiency anemia:
   1. Serum iron is deficient.
   2. TIBC is very high.
   3. Serum ferritin = <10 ng/dL
   4. Free RBC protoporphyrin is high.
   5. RDW is high.
   6. RBC survival time is slightly less.
5. Peripheral blood smears show microcytes and pale, hypochromic RBCs.
   1. There may be leucopenia.
   2. Platelets are high in cases of bleeding.
   3. Reticulocytes are lower than expected in the degree of anemia.
6. Bone marrow shows erythroid hyperplasia.
   1. Iron stain shows deficient iron.

How would you describe Macrocytic Anemia?

1. These are megaloblastic anemias resulting from the deficiency of vitamin B12, folic acid, or a combination of both.

What are the lab findings of macrocytic anemia?

1. Low hemoglobin.
2. MCV > 99 fL.
3. The peripheral blood smear shows macrocytosis and many hypersegmented neutrophils.
4. Occasionally, you may see leucopenia and thrombocytopenia.

What are the causes of macrocytic anemia?

1. Vitamin B12 deficiency.
2. Folic acid deficiency.
   1. Or a combination of both
3. Chemotherapy side effects.
4. In the case of hydantoin therapy.

 How would you describe Hemolytic Anemia?

How will you define hemolytic anemia?

1. Hemolytic anemia is a disorder associated with the decreased life span of RBCs.
2. The shortened life span of RBCs may be an intracorpuscular or extracorpuscular abnormality.
3. The severity depends on the rate of destruction and the removal of RBCs.
4. The normal bone marrow can increase its work by 6 to 8 times, so the anemia may not be apparent until the RBC’s life span reaches only 20 days.

What are the causes of hemolytic anemia?

1. Intrinsic defects like:
   1. Hereditary defects like:
      1. An abnormal RBC membrane detects hereditary spherocytosis.
      2. Inherited RBC enzyme disorders like G-6-phosphate dehydrogenase deficiency.
   2. Disorders of abnormal hemoglobin production, such as sickle cell disease.
   3. Thalassemia syndrome.
   4. Paroxysmal nocturnal hemoglobinuria.
2. Extrinsic defects like:
   1. Chemical and toxic agents.
   2. Infection causing hemolysis.
   3. Hypersplenism.
   4. Immune hemolytic anemia.

How will you diagnose hemolytic anemia?

1. There is a raised bilirubin level.
2. There are increased reticulocytes.
3. There is polychromasia.

How will you summarize lab findings in various anemias?

How will you summarize lab findings in various anemias?

How will you classify anemia based on RDW?

What is the relation between MCV and RDW in various diseases?

What are the abnormalities of RBCs and their etiology?

Type of RBC abnormality	Etiology of the abnormality
Microcytic RBCs Sickle cell Hb structure	Iron-deficiency anemia Thalassemia Sideroblastic anemia Lead poisoning
Macrocytic	Megaloblastic anemia Liver diseases Myelodysplastic syndrome Increased reticulocyte count
Spherocytes	Hereditary spherocytosis Hemolytic anemia Post transfusion
Target cells	Thalassemia Liver diseases Sideroblastic anemia Hemoglobinopathies
Teardrop cells	Severe anemia Pernicious anemia Myeloproliferative anemia
Elliptocytes	Hereditary elliptocytosis Thalassemia Iron-deficiency anemia
Sickle cells	Sickle cell anemia Sickle-thalassemia
Stomatocytes	Malignant tumors Acute alcoholism
Burr cells	Renal diseases Liver diseases Bleeding gastric ulcer Severe burns
Acanthocytes	Alcohol intoxication Post splenectomy Vitamin E deficiency Congenital abetalipoproteinemia
Helmet cells	G-6-PD deficiency Pulmonary emboli
Schistocytes	Hemolytic uremic syndrome Thrombotic idiopathic thrombocytopenia (ITP) Disseminated intravascular coagulopathy (DIC)

How will you summarize lab findings in various anemias?

What are the various forms of red blood cells?

Panic values are:

1. Hb = <5 g/dL or >20 g/dL
2. Hct = <20 % ( leads to heart failure)  or > 60% (leads to spontaneous clotting).

Questions and answers: