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.
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
- Iron deficiency anemia
Clinical suspicion: Microcytic hypochromic anemia.
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.
- 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.
Clinical suspicion: Anemia with thrombocytopenia or pancytopenia with reticulocytopenia. Bone marrow aspirate often shows dry tap.
- Anemia of chronic diseases.
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
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.
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).
- Drug induced:
Clinical suspicion: Once the diagnosis of hemolytic anemia is established drug intake must be excluded.
- Underlying hematological malignancy
- Collagen vascular disorders
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).
b. non-immune hemolysis
Direct Coombs test negative
- 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)
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Glycolytic pathway enzyme deficiency (pyruvate kinase, hexokinase)