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Category: Hematology | Pathology

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Anemia overview

Published: November 02, 2017. Updated: November 02, 2017

Anemia is defined as a decrease in red cell mass. Direct measurement of red cell mass is complicated and expensive often involving the infusion of radiolabeled erythrocytes. As a result, anemia is defined on the basis of more practical measurements such as blood counts, hemoglobin concentration, and hematocrit.

Hematocrit = 42%, Hemoglobin = 14 in males and a Hematocrit = 37% Hemoglobin 12 in females.


In its simplest form, anemia is classified based on whether it presents with or without an increase in absolute reticulocyte count

The normal physiological reaction to anemia is to increase bone marrow production of red cells. This is manifested by an increased reticulocytic count.

In patients who do not have a healthy bone marrow, red cell production is not increased and the reticulocytic count is not increased. This occurs in cases of bone marrow dysfunction or inadequate resources (e.g. iron) to produce red cells.

Absolute reticulocyte count = % of reticulocytes x RBC count and should be </= 100,000

1. Anemia without increased reticulocytes

Decreased MCV

  • Iron deficiency anemia
    Clinical suspicion: Microcytic hypochromic anemia.
  • Thalasthemia
    Clinical suspicion: microcytic hypochromic anemia without increase in reticulocyte count not caused by iron deficiency with morphological abnormalities in peripheral blood smear. In severe cases bone abnormalities & splenomegaly.

Normal MCV

  • Myelodysplastic syndrome
    Clinical suspicion: Normocytic anemia & reticulocytopenia not diagnosed conventionally will require a bone marrow aspirate and subsequently a bone marrow biopsy OR macrocytic anemia not found to be due to folate or B12 deficiencies. More advanced cases may present with evidence of myelodysplasia.
  • Aplastic
    Clinical suspicion: Anemia with thrombocytopenia or pancytopenia with reticulocytopenia. Bone marrow aspirate often shows dry tap.
  • Anemia of chronic diseases.

Increased MCV

Is almost always due to

  • B12 or
  • folate deficiencies.

Clinical suspicion: Macrocytic anemia with absolute reticulocytopenia.

Diagnosis: Serum B12 and RBC folate are measured.

If results of above are equivocal then both methylmalonic acid and homocysteine are measured. Both are elevated in B12 deficiency whilst only homocysteine is elevated in folate deficiency.

2. Anemia with increased absolute reticulocyte count

This means that the patient has a healthy bone marrow which is reacting to the anemia as it should but not able to compensate it. Anemia here is caused by factors outside the bone marrow such as blood loss or destruction (hemolysis).

Is either due to hemorrhage or hemolysis (increased peripheral loss)

1. Blood loss


2. Hemolytic anemia

Elevated indirect bilirubin and LDH

Hemolysis is the rapid breakdown of RBCs which manifests itself with jaundice and anemia. Hemolytic anemia is diagnosed by the presence of elevated indirect bilirubin and LDH in addition to anemia with increased retics.

Once hemolysis is established, the cause is determined using the clinical history, Coombs' test and red cell morphology on blood smear.

The history determines whether the hemolytic anemia is congenital or acquired.

Acquired hemolytic anemias result from immune or non-immune causes which can be easily determined by a direct (antiglobulin) Coomb test.


  • Intravascular hemolysis is hemolysis of RBCs inside the vascular system and
    Extravascular hemolysis is RBC destruction in the reticuloendothelial system particularly the spleen.
  • Haptoglobin is a protein that removes free Hgb, hence it decreases in cases of intravascular hemolysis but remains normal in cases of extravascular hemolysis.

i. Acquired hemolysis

History suggestive of acquired hemolysis

acquired hemolysis is either of immune cause or non-immune cause.

a. autoimmune hemolysis

Direct Coombs test positive

The direct Coombs' (antiglobulin) reaction is used to detect the presence of immunoglobulin or complement on the red-cell membrane and to determine the specific class of immunoglobulin or complement present.

1. Warm antibody hemolytic anemia (IgG):

 Direct Coombs test IgG / IgG & C3

Antibodies interact best with RBCs at 37? C. Hemolysis is primarily extravascular (serum haptoglobin normal).

  1. Drug induced:
    Clinical suspicion: Once the diagnosis of hemolytic anemia  is established drug intake must be excluded.
  2. Underlying hematological malignancy
  3. Collagen vascular disorders
  4. Infections
  5. Idiopathic

1. Cold antibody hemolytic anemia (IgM):

 Direct Coombs test  C3 only

Cold antibody hemolytic anemia:
Antibodies interact best with RBCs at 4? C. Hemolysis is mainly in the liver but maybe intravascular (serum haptoglobin decreased).

  1. Paroxysmal cold hemoglobinuria
  2. Cold agglutinin disease
  3. Mycoplasma and viral infections
  4. idiopathic

b. non-immune hemolysis

Direct Coombs test  negative

  • Hypersplenism
  • Microangiopathic
  • Chemical agents
  • Physical agents
  • Lipid abnormalities
  • Infectious agents

ii. Congenital hemolysis

History suggestive of congenital hemolysis

Diagnosis is suggested by blood smear examination.

Secondary to Membrane Abnormalities

Secondary to Abnormal Hemoglobin (Hemoglobinopathies)

Secondary to Disturbed Metabolism (Enzymopathies)

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