Normocytic anaemia

• There are 3 As and 2 Hs for normocytic anaemia:

   

  A – Acute blood loss

  A – Anaemia of chronic disease

  A – Aplastic anaemia

  H – Haemolytic anaemia

  H – Hypothyroidism

  Pregnancy too.
• Since the size of the RBCs isn’t altered in normocytic anaemia, the decreased haemoglobin must be due to another cause, either haemolysis (intravascular or extravascular) or underproduction of normal-sized RBCs.
• The reticulocyte count enables differentiation between haemolysis or underproduction. A high reticulocyte count would indicate that the bone marrow was functioning normally and therefore the anaemia is not likely to be due to underproduction. Unlike microcytic anaemias, normocytic anaemias are usually normochromic.
• Anaemia of chronic disease

  -          Malignancy, chronic infections, autoimmune conditions – causes the liver to produce acute phase reactants such as hepcidin. Hepcidin “hides” the iron in ferritin to reduce availability in the serum. Anaemia of chronic disease starts out as normocytic anaemia but it can progress to microcytic anaemia.
• Anaemia of chronic disease lab findings:

  ·       Normal MCV (80-100) or low MCV (<80)

  ·       Serum iron: low

  ·       Transferrin saturation: low

  ·       Ferritin: high

  ·       TIBC: low
• Hereditary spherocytosis (haemolytic)

  -          Inherited defect of RBC cytoskeleton membrane proteins such as ankyrin and sprectrin – prevents easy manoeuvrability through the splenic infrastructure – RBCs get struck and are destroyed by the spleen.

  Splenectomy is often performed.
• Haemolytic anaemia: Serum uric acid is increased due to lysed RBCs.
• Sickle cell anaemia (haemolytic)

  -          Autosomal recessive mutation in the beta-globin chain of haemoglobin – valine replaces glutamic acid

  -          Intravascular haemolysis may occur due to the deformed sickle shape of the RBC – spleen has a role in the more predominant extravascular haemolysis of the misshapen cells
• Lab findings in sickle cell:

  ·       Reticulocyte count: increased due to compensation by the bone marrow for intravascular/extravascular haemolysis

  ·       Serum uric acid: increased due to lysed RBCs

  ·       Blood film: sickling of erythrocytes and features of hyposplenism including target cells and Howell-Jolly bodies
• Blood film: which haemolytic disease is this?

  Sickle cell anaemia

  A) Howell jolly bodies

  B) sickle cell anaemia

  
• Paroxysmal nocturnal haemoglobinuria (haemolytic)

  -          Defect in glycosylphosphatidylinositol that leaves cells more susceptible to the complement system

  -          When shallow breathing occurs during sleep, there is CO​2 retention, which results in a state of mild respiratory acidosis. This environment activates complement to lyse RBCs because the protective factor (GPI) is lacking.

  Lab findings:

  ·       Reticulocyte count: normal

  ·       Serum uric acid: increased due to lysed RBCs
• Glucose-6-phosphate dehydrogenase deficiency (haemolytic)

  -          Deficiency of G6PD makes RBCs more susceptible to oxidative stress

  -          Normally G6PD creates nicotinamide adenine dinucleotide phosphate (NADPH) which in turn creates reduced glutathione to protect the cell from oxidative injury.

  -          Lack of G6PD results in intravascular haemolysis due to destruction via oxidative stress

  
  

  Lab findings:

  ·       Reticulocyte count: increased

  ·       Serum uric acid: increased due to lysed RBCs
• Immune haemolytic anaemia (IgG or IgM mediated)(haemolytic)

  -          IgG-mediated haemolysis is usually extravascular, while IgM-mediated haemolysis is intravascular.

  
  

  Lab findings:

  ·       Reticulocyte count: increased due to compensation by the bone marrow for intravascular/extravascular haemolysis

  ·       Serum uric acid: increased due to lysed RBCs
• Microangiopathic haemolytic anaemia (haemolytic)

  -          RBCs destroyed because of structural issues with the vasculature such as microthrombi, prosthetic heart valves, aortic stenosis – RBCs get torn on these structures – creating schistocytes.

  A) schistocytes

  
• Aplastic anaemia is rare disease condition in which the bone marrow does not produce adequate number of new blood cells. This causes tiredness, shortness of breath, rapid heart rate, unexplained bruising, nose bleeds, headache and fever.
• Hypothyroidism causes a mild hypoproliferative normocytic anaemia due to the loss of the stimulatory effect of thyroid hormones on erythropoiesis.