Anemia:- Part 1 – Anemia Classification, Diagnosis, and Routine Work up
Anemia
Sample for Anemia
- EDTA blood is needed.
- For RBC morphology, a direct smear is preferred.`
- Bone marrow is also advised.
- Also, a bone biopsy may be needed.
Definition of Anemia
- Anemia is defined as a decrease in hemoglobin concentration depending on the patient’s age and sex.
- The diagnostic criteria are low hemoglobin, low hematocrit (Hct), or decreased RBC count.
Criteria for the anemia:
- Hemoglobin:
- Male = Hb <13.5 g/dL.
- Female = Hb 11.5 g/dL.
- 2 years to puberty = 11.0 g/dL.
- A Newborn = 14.0 g/dL is taken as a lower limit because of the high Hb.
- Hematocrit (Hct)
- Male = <42%.
- Female = <37%.
- In a broad sense, anemia is the blood’s inability to supply adequate O2 to the tissue for proper metabolism.
- These are the most common hematological disorders.
- The diagnosis is essential for the physician to treat the cause of anemia.
Effective erythropoiesis depends upon the following:
- Level of iron and cobalt.
- Vitamin B12.
- Vitamin B6.
- Riboflavin.
- Thiamine.
- Vitamin C.
- Vitamin E.
- Hormones like:
- Androgens.
- Thyroxine.
Types of Hemoglobin:
To understand the anemias, it is better to know the hemoglobin types and structure:
Type of hemoglobin | Structure of hemoglobin | Frequency of the hemoglobin |
At birth | ||
Hb F | α2 / γ2 | 60 to 90% |
Hb A | α2 / β2 | 10 to 40% |
At adult age | ||
Hb A1 |
α2 / β2 | >95% |
Hb A2 |
α2 / δ2 | <3.5% |
Hb F |
α2 / γ2 | <1 to 2% |
Role of hemoglobin in O2 transport (Hb/O2 dissociation curve):
- The RBCs carry O2 from the lung to the tissue and bring CO2 in the venous blood to the lung.
- This is dependent upon the 2,3-diphosphoglycerate (2,3-DPG).
- When the O2 is unloaded, the β-chain of Hb has pulled apart, permitting the entry of the metabolites 2,3-DPG resulting in a lower molecule affinity for O2.
- O2 saturation is an indicator of the % of Hb saturated with O2.
- When 92% to 100% of the Hb carries O2, the tissues adequately provide the O2 supply, which means normal O2 dissociation.
- Normally O2 exchange takes place:
- 95% saturated arterial blood with a mean arterial O2 tension of 95 mmHg.
- 70% saturated venous blood with a mean venous O2 tension of 40 mmHg.
- So the curve’s normal position depends upon the concentration of 2,3-DPG, H+ ions, and CO2 in the RBCs and the Hb molecule structure.
Hemoglobin functions:
- RBCs in arterial blood carry O2 from the lungs to the tissue and take back CO2 in the venous blood.
- This main function is with the help of hemoglobin (Hb) molecules, as the Hb molecule load and unload the O2.
- α1β1 and α2β2 globin stabilize the molecule.
Anemia classification:
Anemia may be classified roughly based on Hb level:
- Severe anemia when the Hb is <7 g/dL.
- Moderate when the Hb is 7 to 10 g/dL. This group will not produce evident S/S. in most of the cases.
Anemia classification based on RBC morphology:
- Normochromic and normocytic anemias are due to:
- Anemia of acute hemorrhage.
- Hemolytic anemia.
- Anemia due to chronic diseases.
- Hypochromic and microcytic anemias are due to:
- Iron deficiency anemia.
- Thalassemia.
- Normochromic and macrocytic anemias are due to:
- Vit. B12 deficiency.
- Folate deficiency.
Anemia classification based on physiological abnormality:
- Defective maturation of erythropoiesis.
- Hemolytic anemia where is the increased breakdown of the RBCs.
- Defect due to an increase in RBC precursors compared to the degree of anemia.
Anemia classification based on etiology:
- Increased RBCs destruction due to intra or extra red blood cell defects.
- Increased blood loss, which may be acute or chronic.
- Defective RBCs formation due to Lake of factors necessary for erythropoiesis.
Anemia classification based on the category:
- increased destruction of the RBCs
- Hemolytic anemia (nonimmune).
- Immune hemolytic anemia.
- Anemia due to blood loss in hemorrhage.
- Nutritional deficiency like folate or vitamin B12 deficiency.
- Toxicity due to drugs.
- Infections.
- Infiltration of the bone marrow by the cancer cells.
- Hereditary or acquired defect in the RBCs.
- Hematopoietic stem cell arrest or damage.
- Idiopathic or unknown cause.
Anemia classification based on RBC indices:
- Normocytic:
- MCV is 80 to 100 fl (femtoliter).
- MCHC = 32 to 36%
- Macrocytic:
- MCV = >100 fl.
- Microcytic and hypochromic.
- MCV = <80 fl.
- MCHC = <32%.
Type of anemia MCV fl MCHC% Normocytic and normochromic 80 to 100 32 to 36 Microcytic and hypochromic <80 <32 Macrocytic >100
Differentiating points of various anemias:
Characteristics findings | Microcytic hypochromic | Normocytic normochromic | Macrocytic |
MCV | <80 fl (decreased) | 80 to 95 fl (normal) | >95 fl (increased) |
MCH | <27 pg (decreased) | ≥27 pg (normal) | Increased |
MCHC | Decreased | Normal | Normal |
Etiological factors |
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Laboratory Criteria for the diagnosis of Anemias:
- Hemoglobin when it is less than 12 to 13 G/dL.
- Hematocrit when it is less than 36 to 41%.
- Reticulocyte count was normal at 0.5 to 1.5%.
- MCV is a better choice to classify the anemias and their differentiation. This is useful for the screening of occult alcoholism.
- If MCV is high, then advise:
- Reticulocytes count.
- Vit.B12.
- Folate level.
- If MCV is low, advised:
- Serum Iron.
- Iron binding capacity (TIBC).
- If the above two tests are low, advise Ferritin and Bone marrow examination.
- If normal, then advise electrophoresis.
- If MCV is normal, then advise:
- Serum Iron.
- Iron Binding Capacity. (TIBC).
- Comb’s test.
- Peripheral blood for RBC morphology.
Routine workup of the patient with anemia needs:
- The patient’s detailed clinical history for diagnosis, physical examination, signs, and symptoms with the following lab workup.
- Hemoglobin and hematocrit.
- Red blood cell count.
- Blood indices.
- MCH has limited value in the differential diagnosis of anemias. This is instrumental calibration.
- MCHC is also instrumental calibration, and changes occur very late in the iron-deficiency anemia when anemia is very severe.
- This is better to evaluate hypochromasia than MCH.
- Red cell distribution width (RDW) helps to classify the anemia with the help of MCV.
- RDW is more sensitive to the differentiation of the microcytic anemia than the macrocytic RBCs cause.
- This has no value in patients without anemia.
- Serum iron (Normal = 50 to 150 µg/dL).
- Serum total iron helps in the diagnosis of anemia.
- It differentiates between hemochromatosis and hemosiderosis.
- It should be measured along with TIBC for evaluation of iron deficiency.
- This also helps to evaluate the acute iron toxicity in children.
- Total iron-binding capacity (TIBC = Normal = 250 to 450 µg/dL).
- It helps in the differential diagnosis of anemias.
- It should be done along with serum iron to evaluate the % saturation for the diagnosis of iron deficiency anemia.
- Transferrin: Serum Transferrin level is needed for the D/D of the anemia.
- Percent transferrin saturation (normal % transferrin saturation = 20% to 50%).
- Calculation of the % transferrin saturation = Serum iron ÷ TIBC x 100 = Transferrin normally 33% is saturated.
- This is used for the D/D of the anemias.
- This helps in the screening of hereditary spherocytosis.
- Ferritin: Serum ferritin (normal = 20 to 250 ng/dL).
- It correlates with the total body iron stores.
- It differentiates iron deficiency or excess.
- It correlates with total body iron stores.
- It will predict and monitor iron deficiency.
- It will give an idea about the iron-deficiency anemia treatment effectiveness.
- It differentiates iron deficiency from chronic diseases.
- It monitors the iron status in patients with chronic kidney diseases with or without dialysis.
- It is used to study the population’s iron level and response to iron supplements.
- It can detect iron overload and monitor iron accumulation.
- It can help to guide the response to iron depletion therapy.
- Peripheral blood smear.
- This will inform the abnormality of the RBC shape, size, and any kind of inclusions.
- 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.
- Also, find the abnormal white cells and the assessment of the platelets.
- It can find the blast cells like normoblast or granulocytes blast cells.
- Reticulocyte count.
- The normal range is 0.5 to 2.5%, and the absolute count is 25 to 125 x 109/L.
- Reticulocytes are raised in anemia because of the erythropoietin raised level.
- After the acute hemorrhage:
- Erythropoietin level rises in 6 hours.
- Reticulocyte level increases in 2 to 3 days, and the peak level reaches 6 to 10 days.
- Reticulocytes will be raised until the Hb becomes normal.
- In the case of anemia, if there is no raised reticulocyte count, it means bone marrow abnormality or lack of erythropoietin stimulus.
- White blood cells count and platelets count. This will rule out the pancytopenia from the anemia.
- In hemolysis or hemorrhage, the neutrophils and the platelets are raised.
- In leukemias also, the white cells are raised.
- Bone marrow examination.
- Bone marrow may be aspirated or can take the biopsy.
- This will give the cellularity myeloid: erythroid ratio, presence of abnormal cells like cancer cells infiltrate.
- Can do Special stains like iron.
Signs and symptoms of the anemias:
Clinically S/S seen are:
- The main symptoms are due to cardiovascular system adaptation.
- There are increased stroke volume, tachycardia, and the Hb O2 dissociation curve changes.
- Hyperdynamic circulation leads to tachycardia, a bounding pulse, systolic murmurs, especially at the apex, and cardiomegaly.
- Older adults may find S/S of congestive heart failure.
- There are increased stroke volume, tachycardia, and the Hb O2 dissociation curve changes.
- In some of the patients with anemia, there is no S/S, while mild anemia may have severe S/S.
- Acute onset effect: There is an effect on the speed of onset; acute onset has more S/S compared to the slow onset.
- The severity of the anemia: In the case of mild anemia, there is no S/S.
- When the Hb is <9 to 10 g/dL, it may show S/S.
- Even Hb as low as 6 g/dL may not produce severe S/S.
- Age: Older people tolerate less as compared to young people.
- There is pallor on the face, and better judged from the tongue.
- The patient will feel weakness and fatigue.
- There are lethargy and malaise.
- On exertion, there is dyspnoea and palpitation.
- The older patients may have cardiac failure, angina, or intermittent claudication or confusion.
- There may cause retinal hemorrhage, and this may complicate anemia of rapid onset.
- The patient may like to eat clay, ice, and starch.
- The patient may have syncope after the exercise.
- They may have dizziness and headaches.
- There is tinnitus or vertigo.
- Usually, these patients are irritable.
- These patients may have gastrointestinal symptoms.
- These patients may have difficulty sleeping or concentrating.
Specific Signs of anemia are:
- K0ilonychia, which is spoon-shaped nails. This is usually seen in:
- Iron-deficiency anemia.
- Jaundice with hemolytic or megaloblastic anemia.
- Leg ulcers in Sickle cell anemia.
- Other hemolytic anemias.
- Bone deformities are seen in thalassemia and other severe congenital anemia.
- There may be infections and bruising with anemia due to bone marrow failure related to thrombocytopenia and neutropenia.
Normal adult blood indices values:
RBCs values | Male | Female |
Hemoglobin (Hb g/dL) | 13.5 to 17.5 g/dL | 11.5 to 15.5 g/dL |
Hematocrit (Hct % or Packed cell volume = PCV) | 40 to 52 % | 36 to 48% |
RBC count | 4.5 to 6.5 x1012 /L | 3.6 to 5.6 x 1012/L |
Mean cell volume (MCV) | 80 to 95 fL | |
Mean cell hemoglobin (MCH) | 27 to 34 pg | |
Mean cell hemoglobin concentration (MCHC) | 30 to 35 g/dL | |
Reticulocytes count | 25 to 125 x 109/L |
Types of Anemias
Anemia is divided based on RBCs indices (MCV) into the following broad categories:
- Microcytic, MCV <80 fl.
- Normocytic, MCV 80 to 100 fl.
- Macrocytic, MCV >100 fl.
Normochromic, Normocytic Anemia:
Lab findings:
- Low hemoglobin.
- Normal MCV 80 to 95 fL.
- Normal MCH ≥27 pg.
- Normal MCHC.
- Mostly these are due to acute blood loss.
The peripheral blood smear shows normal-looking RBCs and normal RBCs indices.
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- The RBCs produced by the bone marrow are normal, but the number of RBCs in circulation is reduced for many reasons.
The causes of normochromic and normocytic anemia are:
- Iron deficiency in the early stages.
- Acute blood loss.
- Chronic diseases of the kidneys and the liver.
- Infiltration by leukemia and multiple myeloma.
- Drugs like chloramphenicol cause aplastic anemia.
- Acquired hemolytic anemia may be from the prosthetic surgery of the heart.
- Pregnancy due to increased plasma volume.
- Overhydration.
Microcytic, hypochromic anemia:
- These are the most common type of anemia, and iron deficiency is the most common cause.
Causes of microcytic hypochromic anemia:
- This is due to iron deficiency caused by decreased iron intake in the diet or impaired absorption.
- Iron deficiency anemia.
- Lead poisoning.
- Thalassemia.
- There may be an increased iron loss by chronic bleeding.
- There may be an abnormality in iron metabolism.
- Increased demand by the body in:
- Infancy.
- Pregnancy.
- Lactation.
- Due to cancer.
- Hemorrhoids.
- Hookworms.
- Drugs like salicylates (aspirin).
Lab findings of microcytic hypochromic anemia:
- Low hemoglobin, males <12 g/dL and females <10 g/dL.
- Low MCV <80 fL.
- MCH < 27 pg.
- Findings in the iron-deficiency anemia:
- Serum iron is deficient.
- TIBC is very high.
- Serum ferritin = <10 ng/dL
- Free RBCs protoporphyrin is high.
- RDW is high.
- RBC survival time is slightly less.
- Peripheral blood smears show microcytes and pale, hypochromic RBCs.
- There may be leucopenia.
- Platelets are high in case of bleeding.
- Reticulocytes are low than expected in the degree of anemia.
- Bone marrow shows erythroid hyperplasia.
- Iron stain shows deficient iron.
Macrocytic Anemia:
- These are basically megaloblastic anemias resulting from the deficiency of vitamin B12, folic acid, or a combination of both two.
Lab findings of macrocytic anemia:
- Low hemoglobin.
- MCV > 99 fL.
- The peripheral blood smear shows macrocytosis and many hypersegmented neutrophils.
- Occasionally may see leucopenia and thrombocytopenia.
Causes of macrocytic anemia:
- Vitamin B12 deficiency.
- Folic acid deficiency.
- Or a combination of both
- Chemotherapy side effects.
- In the case of hydantoin therapy.
Hemolytic Anemia:
Definition of hemolytic anemia:
- Hemolytic anemia is a disorder associated with the decreased life span of RBCs.
- The shortened life span of RBCs may be an intracorpuscular or extracorpuscular abnormality.
- The severity depends on the rate of destruction and the removal of RBCs.
- The normal bone marrow can increase its work by 6 to 8 folds, so the anemia may not be apparent until the RBC’s life span reaches only 20 days.
Causes of hemolytic anemia:
- Intrinsic defects like:
- Hereditary defects like:
- An abnormal RBC membrane detects hereditary spherocytosis.
- Inherited RBC enzyme disorders like G-6-phosphate dehydrogenase deficiency.
- Disorders of abnormal hemoglobin production like sickle cell disease.
- Thalassemia syndrome.
- Paroxysmal nocturnal hemoglobinuria.
- Hereditary defects like:
- Extrinsic defects like:
- Chemical and toxic agents.
- Infection causing hemolysis.
- Hypersplenism.
- Immune hemolytic anemia.
Lab findings of hemolytic anemia:
- There is a raised bilirubin level.
- There are increased reticulocytes.
- There is polychromasia.
Table showing findings in various anemias:
Type of anemia | Hb | MCV | MCH | MCHC |
---|---|---|---|---|
Iron deficiency | low | low | low | low |
Megaloblastic | low | high | high | normal |
Thalassemia | low | low | low | low |
Chronic illness | low | low | low | low |
Characteristic findings in various Anemias:
Anemia type |
HB |
MCV |
MCH |
MCHC |
Ferritin |
Iron binding capacity |
serum iron |
RDW |
Iron deficiency | low | low <76 fl | low | low/normal | decreased | increased | decreased | increased |
Megaloblastic | low | high >100 fl/cell |
increased >32 pg |
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 |
normal or increased |
increased |
Beta Thalassemia | low | low | low | low | increased/normal | normal | increased/normal | increased |
Aplastic anemia | low | increased | normal | normal | normal |
Classification of anemia based on RDW:
Cell size |
Normal RDW |
High RDW |
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Mean corpuscular volume (MCV) and Red cell distribution (RDW) in relation to various diseases:
Red cell distribution (RDW) | Mean corpuscular volume (MCV) | Etiology (causes ) |
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Abnormalities of RBCs 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 |
TIBC | Increased | Normal | Normal | Normal | Normal | Normal | Normal | Normal | Low |
Ferritin level | Low | Increased | Increased | Normal | Increased or normal | Increased | Normal | Normal | Normal |
Folate level | Normal | Normal | Low | Normal | Normal | Normal | 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 | |
Bilirubin level | Normal | Mild increase | Mild increase | Normal | Increased | Increased | Increased | Normal | Normal |
Panic values are:
- Hb = <5 g/dL or >20 g/dL
- Hct = <20 % ( leads to heart failure) or > 60% (leads to spontaneous clotting).
Questions and answers:
Q 1: Does red cell distribution (RDW) differentiate between Thalassemia, anemia of chronic diseases, and iron deficiency anemia?
Q2: What will happen to the following laboratory parameters in hemolytic anemia:
- Reticulocytes 2. RDW 3. Indirect bilirubin 4. Haptoglobin
Answers: Q1 = RDW is usually normal in Thalassemia and anemia of chronic diseases while raised in iron deficiency anemia.
Q2 = Indirect bilirubin, reticulocytes, and RDW are increased, while haptoglobin is decreased.
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Thanks for the remarks. You can see other topics on labpedia.net.
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