Anaemia and Polycythaemia Flashcards
What is anaemia?
A reduction in the amount of Hb in a given volume of blood below what would be expected in comparison with a healthy subject of the same age + gender
RBC + Hct usually also reduced
Other than a reduction in the absolute amount of haemoglobin in the blood stream, what else could cause anaemia?
Increase in plasma volume (decreases the Hb concentration)
Why would anaemia from an increase in plasma volume only be transient in a healthy individual?
Excess fluid would be excreted
State 4 mechanisms of anaemia.
Reduced production of RBC’s/Hb in the bone marrow
Loss of blood from the body (haemorrhage)
Reduced survival of RBC’s (haemolytic)
Pooling of RBC’s in a very large spleen
For each type of anaemia, state whether they are usually hypochromic, normochromic or hyperchromic.
Microcytic: hypochromic
Normocytic: normochromic
Macrocytic: normochromic
State 2 common causes of microcytic anaemia.
Defect in Haem synthesis: Iron deficiency, Anaemia of chronic disease
Problem with globin synthesis: Alpha thalassemia, Beta thalassemia
What mechanism usually causes macrocytic anaemia?
Abnormal haemopoiesis- red cell precursors continue to synthesise Hb + other proteins but fail to divide
Thus, cells end up larger than normal
What is megaloblastic erythropoiesis? Describe the appearance of a megaloblast.
A delay in the maturation of the nucleus while the cytoplasm continues to mature + the cell continues to grow
= a cause of macrocytic anaemia
Large + show nucleo-cytoplasmic dissociation
What is an alternative mechanism of macrocytosis?
Premature release of cells from the bone marrow
Reticulocytes are ~ 20% larger than mature red cells so reticulocytosis would increase the MCV
State the 2 most common causes of megaloblastic anaemia.
B12 deficiency
Folate deficiency
State 5 common causes of macrocytic anaemia.
Drugs that interfere with DNA synthesis (e.g. chemotherapy)
Liver disease
Ethanol toxicity
Recent major blood loss with adequate iron stores (reticulocytes increased)
Haemolytic anaemia (reticulocytes increased)
State 3 mechanisms of normocytic normochromic anaemia.
Recent blood loss
Failure to produce RBCs
Pooling of RBCs in the spleen
State 5 causes of normocytic normochromic anaemia.
Peptic ulcer Oesophageal varices Trauma Failure of production of RBC's: Early stages of iron deficiency, ACD, Renal failure, Bone marrow failure/ infiltration Hypersplenism
Define haemolytic anaemia.
Anaemia resulting from shortened survival of RBC’s in the circulation
Can result from intrinsic abnormality of cells or extrinsic factors acting on normal cells
State 2 different classifications of haemolytic anaemia.
Inherited: abnormalities of the cell membrane, Hb or the enzymes in the RBC
Acquired: extrinsic factors e.g. micro-organisms, chemicals or drugs
Intravascular: if there is very acute damage to the red cell
Extravascular: when the spleen removes defective red cells
State 4 inherited abnormalities that can cause haemolytic anaemia.
Abnormal red cell membrane
Abnormal Hb
Defect in the glycolytic pathway e.g. pyruvate kinase deficiency
Defect in enzymes of the pentose shuttle e.g. G6PD deficiency
State 3 acquired abnormalities that cause haemolytic anaemia.
Damage to the red cell membrane e.g. AIHA
Damage to the whole red cell
Oxidant exposure
Explain how G6PD Deficiency can cause haemolytic anaemia.
Oxygen-carrying role of RBC’s means they are at constant risk of oxidant damage
G6PD is part of the pentose phosphate pathway
G6PD deficiency is very susceptible to oxidant damage + thus HA, as lacking enzyme needed to protect the cell
When would you suspect haemolytic anaemia?
Otherwise unexplained anaemia that is normochromic + usually normocytic or macrocytic
Morphologically abnormal red cells
Increased RBC turnover e.g. high BR
Increased bone marrow activity
What does the presence of fragments in the blood film suggest? What condition can cause this?
Suggests RBC’s are being broken down within the circulation (in small vessels)
Microangiopathic haemolytic anaemia
State 2 important signs of haemolytic anaemia.
Jaundice: due to increased break down of RBC’s there is an increase in BR
Increase in BR can also increase risk of gallstones
State examples of inherited diseases causing haemolytic anaemia that have defects at the following sites:
a. Membrane
b. Haemoglobin
c. Glycolytic Pathway
d. Pentose Shunt
Membrane: Hereditary spherocytosis
Haemoglobin: Sickle cell anaemia
Glycolytic Pathway: Pyruvate kinase deficiency
Pentose Shunt: G6PD deficiency
State examples of acquired disease causing haemolytic anaemia that have defects at the following sites:
a. Membrane - immune
b. Whole red cell - mechanical
c. Whole red cell - oxidant
d. Whole red cell - microbiological
Membrane – immune: AI haemolytic anaemia
Whole red cell –mechanical: Microangiopathic haemolytic anaemia
Whole red cell – oxidant: Drugs + chemicals
Whole red cell – microbiological: Malaria
What is hereditary spherocytosis?
Haemolytic anaemia or chronic compensated haemolysis resulting from an intrinsic inherited defect of the red cell membrane
After entering the circulation, cells lose membrane in the spleen + become spherocytic
What are the features of red cells in hereditary spherocytosis?
Become less flexible + are removed prematurely by the spleen
Are LARGE + ROUND
Have an increased MCHC
How does the bone marrow respond to the increased extravascular haemolysis in hereditary spherocytosis?
It increases output of red cells leading to polychromasia + reticulocytosis
What is an effective treatment for hereditary spherocytosis?
Splenectomy
Why is a good diet important in patients with hereditary spherocytosis?
They have increased bone marrow activity + erythropoiesis so they need a supply of B12, folate + iron to keep producing RBC’s
Describe the pattern of inheritance of G6PD deficiency.
X linked recessive
Those affected are usually hemizygous males
What can G6PD deficiency cause?
Intermittent, severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant
What tends to appear in blood films during episodes of severe intravascular haemolysis?
Irregularly contracted cells
What happens to haemoglobin during episodes of severe intravascular haemolysis?
It becomes denatured + forms round inclusions called Heinz bodies
(can get >1 Heinz body per cell unlike Howell-Jolly bodies)
What causes autoimmune haemolytic anaemia?
Results from production of autoantibodies against red cell antigens
Very sudden + dramatic
Describe how autoimmune haemolytic anaemia can lead to spherocytosis.
Immunoglobulin bound to the red cell is recognised by splenic macrophages, which remove parts of the cell membrane leading to spherocytosis.
Complement components can also be bound to the immunoglobulin, + they are also recognised by receptors on splenic macrophages
State 2 causes of spherocytosis.
Hereditary spherocytosis
Autoimmune haemolytic anaemia
Describe the diagnosis of autoimmune haemolytic anaemia.
Finding spherocytes
Increased reticulocyte count
Detecting immunoglobulin on the red cell surface
Detecting antibodies to red cell antigens or other antibodies in the plasma
What is the treatment for autoimmune haemolytic anaemia?
Corticosteroids /other immunosuppressive agents
Splenectomy in severe cases
What is the difference between the mechanism and cause of anaemia? Give an example to illustrate
Mechanism= reduced synthesis of Hb in bone marrow Cause= a condition causing reduced synthesis of haem or globin
What may cause G6PD deficiency?
Extrinsic oxidants in foodstuffs e.g. broad beans, chemicals e.g. naphthalene or drugs e.g. dapsone
What happens to Heinz bodies?
Removed by spleen leaving a defect in the cell “bite cell”
How is microangiopathic haemolytic anaemia treated?
Removing the cause e.g. treating severe hypertension
Plasma exchange when caused by an antibody in the plasma that is leading indirectly to fibrin deposition
