Haem 3 - Anaemia

Question 1

Define Anaemia

Answer 1

Is a reduction in the amount/concentration 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.
The RBC and the PCV/Hct are usually also reduced. It is usually due to the reduction of the absolute amount of haemoglobin in the blood stream.

NOTE: Can be due to an increase in the volume of plasma - in this situation in a healthy person this anaemia won’t persist because excess fluid is excreted from the circulation

Question 2

What are the mechanisms of anaemia?

Answer 2

• Reduced production of red cells/haemoglobin in the bone marrow
• Loss of blood from the body
• Reduced survival of red cells in the circulation
• Pooling of red cells in a very large spleen

Question 3

Describe a mechanism of anaemia

Answer 3

The mechanisms of the anaemia might be reduced synthesis of haemoglobin in the bone marrow
The cause could be a condition causing reduced synthesis of haem or one causing the reduced synthesis of globin.

Question 4

How would you classify anaemia based from cell size?

Answer 4

Microcytic (usually also hypochromic)
Normocytic (usually normochromic)
Macrocytic (usually normochromic)

Question 5

What are the common causes of microcytic anaemia?

Answer 5

Defect in haem synthesis - Iron deficiency, Anaemia of chronic disease (people with chronic infammation –> leading to reduced rate of Hb synthesis)
Defect in globin synthesis (thalassaemia) - alpha and beta thalassaemia (defect in chain synthesis)

Question 6

Describe macrocytic anaemia

Answer 6

Result from abnormal haemopoiesis so that the red cell precursors continue to synthesize haemoglobin and other cellular proteins but fail to divide normally. Fewer are RBC produced.

This anaemia is often associated with decrease number of RBC and lower Hb

Question 7

What are causes of macrocytic anaemia?

Answer 7

• Megaloblastic erythropoiesis - refers to a delay in the maturation of the nucleus while the cytoplasm continues to mature = cell grows.
• Premature release of cells from the bone marrow - reticulocytes are about 20% larger than mature red cells = more reticulocytes in circulation = MCV will increase

Common causes:

1) Megaloblastic anaemia - as a result of lack of vitamin B12 or folic acid
2) Use of drugs interfering with DNA synthesis (chemotherapy - interfere with haematopoeitic cells)
3) Liver disease and ethanol toxicity
4) Recent major blood loss with adequate iron stores (reticulocytes increase as the bone marrow starts spitting them out to compensate)
5) Haemolytic anaemia (reticulocytes also increased because of loss of red cells)

Question 8

What is a megaloblast?

Answer 8

Abnormal bone marrow erythroblast
Larger than normal and shows nucleo-cytoplasmic dissociation - nuclear development is not matching the cytoplasmic development. Examine the bone marrow to confirm megaloblastic anaemia

Question 9

What are the mechanisms of normocytic normochromic anaemia?

Answer 9

Recent blood loss
Failure of production of red cells
Pooling of red cells in the spleen

The MCH and MCV is normal

Question 10

What are the causes of normocytic normochromic anaemia?

Answer 10

1) Peptic ulcer, oesophageal varices, trauma
2) Failure of production of red cells: Early stages of iron deficiency or anaemia of chronic disease, renal failure (erythropoeitin drops), bone marrow failure or suppression (chemotherapy), bone marrow infiltration (spread of cancer)
3) Hypersplenism, e.g portal cirrhosis

Question 11

Define haemolytic anaemia?

Answer 11

Anaemia resulting from shortened survival of red cells in the circulation - this can be due to intrinsic abnormality of the red cells in the circulation or due to extrinsic factors acting on the red cell

Question 12

How can you classify haemolytic anaemia?

Answer 12

Inherited or acquired - extrinsic factors can interact with cells that have intrinsic abnormality

Inherited haemolytic anaemia - abnormalities in the cell membrane, the haemoglobin or the enzymes in the red cell.
Acquired haemolytic anaemia - extrinsic factors such as microorganisms, chemicals or drugs that damage the red cell.

Intravascular or extravascular

Intravascular haemolysis - occurs if there is very acute damage to the red cell. You can see Hb in urine, if haemoloysis is very high
Extravascular haemolysis - occurs when defective red cells are removed by the spleen

Question 13

Haemolytic anaemia - when do you suspect it?

Answer 13

See slides + notes
Unexplained anaemia that is normochromic and usually either normocytic or macrocytic (when reticulocyte count it high)
Evidence of morphologically abnormal red cells
Evidence of increased red cell breakdown
Evidence of increased bone marrow activity

Haemolytic anaemia could be caused by increase turnover of cells = increased RBC breakdown. This means you get an increase in bilirubin leading to jaundice. This increase of bilirubin also means greater chance of forming bile pigment stones in the gallbladder = gall stones

Question 14

List causes of inherited haemolytic anaemia including site of defect and examples

Answer 14

Membrane - hereditary spherocytosis
Haemoglobin - sickle cell anaemia
Glycolytic pathway - pyruvate kinase deficiency
Pentose shunt - glucose-6-phosphate dehydrogenase deficiency

Question 15

List causes of acquired haemolytic anaemia including site of defect and examples

Answer 15

Membrane (immune) - autoimmune haemolytic anaemia
Whole red cell (mechanical) - Microangiopathic haemolytic anaemia
Whole red cell (oxidant) - drugs and chemicals
Whole red cell (microbiological) - malaria

Question 16

Describe hereditary spherocytosis

Answer 16

Haemolytic anaemia or chronic compensated haemolysis resulting from an inherited intrinsic defect of the red cell memebrane - they lose membrane in the spleen after entering the circulation = spherocytes

They are larger, rounder and have increased MCHC

Extravascular haemolysis, less flexible, bone marrow responds to haemolysis by increased output of RBC = polychromasia and reticulocytosis.

Question 17

Haemolysis leads to?

Answer 17

Increase bilirubin, jaundice and gall stones

Question 18

How do you treat spherocytosis?

Answer 18

Only effective treatment is a splenectomy - but many risks so only done in extreme cases. Risk or many infections.
The biconcave disk of the red cells means it can go through the sinusoids in the spleen but the spherocytes can’t because of its round shape. They can’t manoeuvre out so you get early removal of these cells in the spleen.

Good diet to prevent secondary folic acid deficiency/take one folic acid tablet a day

Question 19

What is G6PD?

Answer 19

Glucose-6-phosphate dehyrdogenase

1) Important enzyme in the pentose phosphate shunt/pathway - generates NADPH and pentoses
2) Protection of the red cell from oxidant damage.

Oxidants can be generated in the blood stream during infection or may be exogenous. Oxidants are dangerous if you are deficient in G6DP. See notes for sources of oxidants

Question 20

Describe G6PD deficiency

Answer 20

See notes - causes intermittent, severe intravascular haemolysis as a result of an infection or exposure to exogenous oxidant. Associated with appearance of considerable numbers of irregularly contracted cells.

The haemoglobin is denatured - forms round inclusions (Heinz bodies), which can be detected by a test. Heinz bodies are removed in the spleen leaving a defective cell. Acute haemolysis sometimes requires blood transfusion - prevention is important

Question 21

What is autoimmune haemolytic anaemia?

Answer 21

Results from the production of autoantibodies directed at red cell antigens. This immunoglobulin is then recognised by splenic macrophages which remove parts of the cell membrane –> spherocytosis

Complement components can also be bound to the immunoglobulin molecules - recognised by splenic macrophages

Remember spherocytes can’t get through the sinusoids so easily so prematurely broken down in the spleen.

Question 22

How do you diagnose autoimmune haemolytic anaemia?

Answer 22

Finding spherocytes and an increased reticulocyte count
Detecting immunoglobulin +/- complement on the red cell surface
Detecting antibodies to red cell antigens or other autoantibodies in the plasma

Question 23

How do you treat autoimmune haemolytic anaemia?

Answer 23

Corticosteroids and other immunosupressive agents

Splenectomy for severe cases

Question 24

How do you treat microangiopathic haemolytic anaemia?

Answer 24

MAHA - formation of fibrin mesh that cuts the RBC physically

Removing the cause - treating severe hypertension or stopping causative drug?
Plasma exchange when it is caused by an antibody in the plasma that is leading indirectly to fibrin deposition