Anaemia and Polycythaemia Flashcards
What is anaemia?
A reduction in the amount of haemoglobin in a given volume of blood below what would be expected in comparison with a healthy subject of the same age and gender
Other than a reduction in the absolute amount of haemoglobin in the blood stream, what else could cause anaemia?
An increase in the plasma volume can decrease the haemoglobin concentration
Why would this type of anaemia only be transient in a healthy individual?
The excess fluid would be excreted in a healthy individual
Broadly speaking, state four mechanisms of anaemia.
Reduced production of red blood cells/haemoglobin in the bone marrow
Loss of blood from the body (haemorrhage)
Reduced survival of red blood cells (haemolytic)
Pooling of red blood cells 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 the common causes of microcytic anaemia.
Problem with Haem synthesis Iron deficiency Anaemic of chronic disease Problem with globin synthesis Alpha thalassemia Beta thalassemia
What mechanism usually causes macrocytic anaemia?
It usually results from abnormal haemopoiesis
The cells fail to divide properly
What is megaloblastic erythropoiesis? Describe the appearance of a megaloblast.
Megaloblastic erythropoiesis refers to a delay in the maturation of the nucleus while the cytoplasm continued to mature and the cell continues to grow
A megaloblast is an abnormal bone marrow erythroblast
They are large and show nucleo-cytoplasmic dissociation
What is an alternative mechanism of macrocytosis?
You can get premature release of cells from the bone marrow
Reticulocytes are about 20% larger than mature red cells so reticulocytosis would increase the MCV
State the two most common causes of megaloblastic anaemia.
B12 deficiency
Folate deficiency
State some other 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 (if you’ve lost blood, the bone marrow will start spitting out reticulocytes to compensate)
Haemolytic anaemia (reticulocytosis due to the loss of red cells)
State three mechanisms of normocytic normochromic anaemia.
Recent blood loss
Failure to produce red blood cells
Pooling of red blood cells in the spleen
State five causes of normocytic normochromic anaemia.
Peptic ulcer Oesophageal varices Trauma Failure of production of red blood cells Early stages of iron deficiency and ACD Renal failure Bone marrow failure Bone marrow infiltration Hypersplenism
Define haemolytic anaemia.
Anaemia resulting from shortened survival of red blood cells in the circulation
State two different classifications of haemolytic anaemia.
Haemolysis can be inherited (resulting from abnormalities of the cell membrane, haemoglobin or the enzymes in the red blood cell)
It can be acquired usually resulting from extrinsic factors such as micro-organisms, chemicals or drugs
Haemolytic anaemia can also be described as intravascular if there is very acute damage to the red cell
It can also be classified as extravascular when the spleen removes defective red cells
State some inherited abnormalities that can cause haemolytic anaemia.
Abnormal red cell membrane
Abnormal haemoglobin
Defect in the glycolytic pathway
Defect in the enzymes of the pentose shuttle
State some acquired abnormalities that cause haemolytic anaemia.
Damage to the red cell membrane
Damage to the whole red cell
Oxidant exposure
Explain how G6PD Deficiency can cause haemolytic anaemia.
G6PD is part of the pentose phosphate pathway
This is the only source of reduced glutathione in red blood cells
Because of the oxygen-carrying role of red blood cells, they are at constant risk of oxidant damage
So people with G6PD deficiency are at risk of haemolytic anaemia in states of oxidative stress
When would you suspect haemolytic anaemia?
Otherwise unexplained anaemia that is normochromic and usually either normocytic or macrocytic
Evidence of morphologically abnormal red cells
Evidence of increased red blood cell turnover
Evidence of increased bone marrow activity
What does the presence of fragments in the blood film suggest?
This suggests that red blood cells are being broken down within the circulation (in the small circulation)
What condition causes breakdown of red blood cells in small blood vessels?
Microangiopathic haemolytic anaemia
State some important signs of haemolytic anaemia.
Jaundice – because of the increased break down of red blood cells there is an increase in bilirubin
The increase in bilirubin can also increase the risk of getting 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
a. Membrane Hereditary spherocytosis b. Haemoglobin Sickle cell anaemia c. Glycolytic Pathway Pyruvate kinase deficiency d. Pentose Shunt G6PD deficiency
State examples of acquires 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
a. Membrane – immune Autoimmune haemolytic anaemia b. Whole red cell –mechanical Microangiopathic haemolytic anaemia c. Whole red cell – oxidant Drugs and chemicals d. Whole red cell – microbiological Malaria
What is hereditary spherocytosis?
This is haemolytic anaemia or chronic compensated haemolysis resulting from an intrinsic inherited defect of the red cell membrane
After entering the circulation, the cells lose membrane in the cell and become spherocytic
What are the features of red cells in hereditary spherocytosis?
They are LARGE and ROUND and have an increased MCHC
How does the bone marrow respond to the increased extravascular haemolysis in hereditary spherocytosis?
It increases the output of red cells leading to polychromasia and 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 and erythropoiesis so they need a supply of B12, folate and iron to keep producing red blood cells
Describe the pattern of inheritance of G6PD deficiency.
X linked recessive
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 these episodes of severe intravascular haemolysis?
Irregularly contracted cells
What happens to the haemoglobin during these episodes?
It becomes denatured and forms round inclusions called Heinz bodies
NOTE: you can get more than one Heinz body per cell unlike Howell-Jolly bodies
What causes acute haemolytic anaemia?
Results from the production of antibodies against red cell antigens
This is very sudden and dramatic
Describe how acute haemolytic anaemia can lead to spherocytosis.
The immunoglobulin bound to the red cell is recognised by splenic macrophages, which remove parts of the cell membrane leading to spherocytosis
State two causes of spherocytosis.
Hereditary spherocytosis
Autoimmune haemolytic anaemia
Describe the diagnosis of acute 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 acute haemolytic anaemia?
Corticosteroids or other immunosuppressive agents Splenectomy in severe cases
Which red blood cell parameters are increased in polycythaemia?
RBC
Hct
Hb
What is the term given to a condition where these parameters are increased but the absolute amount of haemoglobin is not increased?
Pseudopolycythaemia (or apparent polycythaemia)
This is due to a decrease in plasma volume
State some causes of polycythaemia.
Blood doping
Elevation of EPO when at altitude
Tumour (renal or other tumour that can secrete high amounts of EPO)
Abnormal function of bone marrow – it can result from inappropriately increased erythropoiesis that is independent of EPO, this is an intrinsic bone marrow disorder called polycythaemia vera
It is a chronic myeloproliferative neoplasm
What are the consequences of polycythaemia?
Hyperviscosity of the blood
This can lead to vascular obstruction
