Anaemia

Question 1

What is anaemia?

Answer 1

• ‘Low Hb for a given volume of blood in comparison with healthy subject of same age and gender’
• An actual absolute reduction in Hb

Question 2

What haematological values are changed in anaemia, and how?

Answer 2

1. Hb - reduced
2. RBC - reduced
3. Hct - reduced

Question 3

1) What else might cause a reduction in Hb which is not an absolute reduction in Hb, as in anaemia?
2) Why can the above pathophysiology not exist in healthy people?

Answer 3

1) Increase in plasma volume
2) Excess fluid is excreted by healthy people

Question 4

List 4 fundamental mechanisms of anaemia - this is different to causes

Answer 4

1. Reduced production in the bone marrow
2. Haemorrhage
3. Haemolytic problem - reduced survival of RBCs in circulation
4. Pooling of RBCs in very large spleen

Question 5

What are the 3 classifications of anaemia - and for each, are they usually hypo-, normo- or hyper- chromic?

Answer 5

1. Microcytic - hypochromic
2. Normocytic - normochromic
3. Macrocytic - normochromic

Question 6

List 2 classes of causes of microcytic anaemia and 2 examples for each

Answer 6

1. Defect in HAEM synthesis

• Iron deficiency anaemia
• Anaemia of chronic disease

2. Defect in GLOBIN synthesis (thalassaemia)

• Defect in alpha chain synthesis (alpha thalassaemia)
• Defect in beta chain synthesis (beta thalassaemia)

Question 7

Describe the cause of macrocytic anaemia

Answer 7

Abnormal haematopoiesis - red cell precursors continue to synthesis haemoglobin and other cellular proteins but fail to divide normally - therefore RBCs end up larger than normal

Question 8

List 5 causes of macrocytic anaemia

Answer 8

1. Megaloblast erythropoiesis secondary to vitamin B12 deficiency
2. Megaloblast erythropoiesis secondary to folic acid deficiency
3. Use of drugs that interfere with DNA synthesis e.g. chemo
4. Reticulocytosis secondary to haemorrhage with adequate iron stores
5. Haemolytic anaemia (+secondary reticulocytosis)

Question 9

1) What are megaloblasts and how are they formed?
2) Give 2 characteristic features of megaloblasts
3) How to detect megaloblasts

Answer 9

1)

• Megaloblasts are abnormal bone marrow erythroblasts
• Delay in nuclear maturation with normal cytoplasmic maturation - so misbalance between nuclear and cytoplasmic maturation in bone marrow erythropoiesis

2)

• Large
• Nucleo-cytoplasmic dissociation

3)

• Can suspect it from peripheral features but mainly you have to conduct bone marrow examination

Question 10

What is reticulocytosis and how does it cause macrocytic anaemia?

Answer 10

• Premature release of cells from the bone marrow - immature rericulocytes which are 20% larger than mature RBCs increase in circulation - therefore higher MCV for given volume and thus macrocytic anaemia occurs

Question 11

Give 2 causes of megaloblastic erythropoiesis

Answer 11

1. Vitamin B12 deficiency
2. Folic acid deficinecy

Question 12

Give 2 causes of reticulocytosis

Answer 12

1. Haemorrhage - due to premature reticulocyte release as bone marrow rushes to compensate for low RBC
2. Haemolytic anaemia - due to premature reticulocyte release as bone marrow rushes to compensate for low RBC

Question 13

What does the term normocytic normochromic anaemia suggest to you in terms of the haematological RBC parameters?

Answer 13

• Normocytic - normal MCV
• Normochromic - Normal MCH

Question 14

What are the 3 mechanisms of normocytic normochromic anaemia?

Answer 14

1. Haemorrhage
2. Failure of RBC synthesis
3. Pooling of RBCs in spleen - hypersplenism and splenomegaly

Question 15

List 8 causes of normocytic normochromic anaemia, including one class of causes with 4 subsections

Answer 15

1. Peptic ulcers
2. Oesophageal varices
3. Trauma

…..

Failure of RBC production

4. Iron deficiency or anaemia of chronic disease
5. Renal disease
6. Bone marrow failure or suppression
7. Bone marrow infiltration

…..

8. Hypersplenism e.g. portal cirrhosis

Question 16

List the 2 classifications from how you can get haemolytic anaemia and outline what usually causes them

Answer 16

1. Inherited - defects of the RB cell
2. 1 CSM defect e.g. hereditary spherocytosis
3. 2 Hb defect e.g. sickle cell
4. 3 Defect in glycolytic pathway e.g. pyruvate kinase deficiency
5. 4 Defect in enzymes of pentose shunt e.g. G6PD deficiency
6. Acquired - extrinsic factors
7. 1 Damage to RBC membrane e.g. AIHA or snake bite
8. 2 Damage to whole RBC e.g. Microangiopathic Haemolytic Anaemia (MAHA)
9. 3 Oxidant exposure - damage to RBC and Hb - e.g. dapsone or primaquine
10. 4 Oxidant exposure leading to precipitation of episodic haemolysis in individuals with enzyme deficiency

Question 17

List the classifications of the mechanisms behind development of haemolytic anaemia and outline when they generally occur

Answer 17

1. Intravascular - occurs if there is very acute damage to the RBC
2. Extravascular - occurs when defective RBCs are removed by the spleen

Question 18

Give 3 functions of G6PD in RBCs

Answer 18

1. Involved in the pentose phosphate pathway that runs parallel to glycolysis and generates NADPH and pentoses
2. G6PD pathway is the only source of reduced glutathione in RBCs
3. G6PD confers protective effect against oxidative free radical damage

Question 19

In what state are people with G6PD deficiency at particular risk of haemolytic anaemia and why?

Answer 19

In states of oxidative stress because G6PD normally protects against oxidative stress. Oxidative stress leads to haemolytic anaemia

Question 20

What is the role of pyruvate kinase in the RBC and why would pyruvate kinase deficiency lead to haemolytic anaemia?

Answer 20

• Pyruvate kinase is involved in the last stage of glycolysis
• A deficiency of pyruvate kinase will result in a RBC with decreased energy and because RBCs cannot synthesise ATP, cellular death occurs

Question 21

List 3 times when you might suspect haemolytic anaemia

Answer 21

1. Evidence of morphologically abnormal RBCs - hereditary elliptocytosis, irregularly contracted cells fragments
2. Evidence of increased red cell breakdown - fragments etc
3. Evidence of increased bone marrow activity

Question 22

What is microangiophathic haemolytic anaemia (MAHA) and what is an indication of it?

Answer 22

• Haemolytic breakdown of RBCs within small blood vessels
• The presence of fragments indicates MAHA because it indicates RBC breakdown within the circulation rather than by the spleen

Question 23

Give 2 treatment methods for Microangiopathic Haemolytic Anaemia (MAHA)

Answer 23

1. Removing the cause e.g. treating severe HTN or stopping a causative drug
2. Plasma exchange when it is caused by an antibody in the plasma that is leading indirectly to fibrin deposition

Question 24

Give 2 signs of haemolytic anaemia and why they occur

Answer 24

1. Jaundice - due to high bilirubin from the breakdown of RBCs
2. Black holes seen on gall bladder radiograph - if you have a high turnover of red cells and thus a build up of bilirubin, there is a greater chance of forminng bile pigment stones in the gall bladder. Particularly in reticulocytosis

Question 25

The following are all sites of defect for inherited haemolytic anaemias, give an example cause for each... 1) Membrane 2) Haemoglobin 3) Glycolytic pathway 4) Pentose shunt

Answer 25

1) Herditary spherocytosis 2) Sickle cell anaemia 3) Pyruvate kinase deficiency 4) Glucose-6-phosphate dehydrogenase deficiency

Question 26

The following are all sites of defect for acquired haemolytic anaemias, give an example cause for each... 1) Membrane - immune 2) Whole red cell - mechanical 3) Whole red cell - oxidant 4) Whole red cell - microbiological

Answer 26

1) Autoimmune haemolytic anaemia 2) Microangiopathic haemolytic anaemia 3) Drugs and chemicals 4) Malaria

Question 27

What can be detected in a blood film with reticulocytosis?

Answer 27

Polychromasia - blue staining indicating juvenile RBCs (reticulocytes)

Question 28

1) What is hereditary spherocytosis and why does it occur? 2) List 4 characteristic features of spherocytic RBCs 3) What type of haemolysis does it result in and why does it result in this haemolysis? 4) What is the treatment for hereditary spherocytosis?

Answer 28

1) * Inherited intrinsic defect of the RBC CSM in which the CSM loses membrane and the cells become spherical 2) 1. Larger 2. Rounder 3. Increased MCHC 4. Less flexible 3) * Extravascular haemolysis * Normally the biconcave shape of RBCs allow them to escape the splenic sinusoids but spherocytes can't so they are removed early by the spleen 4) Splenectomy

Question 29

Why can you become vitamin deficient after haemolytic anaemia, and what vitamins will you be deficient in?

Answer 29

* Vitamin B12, folic acid, iron deficient * Because all these are necessary for RBC synthesis and in haemolytic anaemia, there is increased RBC turnover resulting in depletion of these vitamins

Question 30

List some extrinsic oxidants

Answer 30

1. Food - e.g. broadbeans 2. Chemicals - e.g. napthalene 3. Drugs - e.g. dapsone, primaquine

Question 31

Where is the gene for G6PD usually carried, and so in whom does G6PD deficiency occur?

Answer 31

* On the X chromosome * Hemizygous males and occasionally homozygous females

Question 32

G6PD deficiency usually causes ....., severe ..... haemolysis as a result of ..... or exposure to an ..... .....

Answer 32

G6PD deficiency usually causes intermittent, severe haemolysis as a result of infection or exposure to an exogenous oxidant

Question 33

Episodes of intravascular haemolysis are associated with the appearance of considerable numbers of .....

Answer 33

.....irregularly contracted cells

Question 34

1) What are heinz bodies and why do they occur? 2) How do they differ from Howell-Joly bodies?

Answer 34

1) Round inclusions that occur due to haemoglobin denaturing. They are removed by the spleen, leaving a defect in the cell 2) You can get more than one Heinz body in one cell, unlike Howell-Joly bodies

Question 35

Give 2 causes of spherocytosis

Answer 35

1. Hereditary Spherocytosis 2. Autoimmune Haemolytic Anaemia

Question 36

What is the pathophysiology of acute haemolytic anaemia?

Answer 36

* Production of antibodies against RBC antigens * The immunoglobulin bound to the RBC is recognised by splenic macrophages, which removes parts of the CSM, leading to spherocytosis * The combination of rigidity, antibody recognition and complement recognition on the RBC CSM by splenic macrophages by splenic receptors also leads to removal of the red cells from circulation by the spleen

Question 37

3 ways to diagnose autoimmune haemolytic anaemia?

Answer 37

1. Finding spherocytes and an increased reticulocyte count 2. Detecting immunoglobulin on the _RBC CSM_ 3. Detecting antibodies to RBC antigens or other antibodies in the _plasma_

Question 38

2 treatment methods for autoimmune haemolytic anaemia?

Answer 38

1. Corticosteroid and other immunosuppressive agents 2. Splenectomy for severe cases