anil - haematology

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Anil - Haematology




MCD Year 2

Anil Chopra


1Haematology 1 - Iron deficiency

4Haematology 2 B12 & Folic Acid Deficiency

7Haematology 3 Haemoglobin and Thalassaemia

10Haematology 4 Abnormal White Cell Counts

14Haematology 5 - Blood Diagnostic Parameters

17Haematology 6 Anaemia and Polycythaemia

21Haematology 7 Haemostasis

25Haematology 8 Abnormalities of Haemostasis

29Haematology 9 Transfusion

Haematology 1 - Iron deficiency

Anil Chopra

1. Describe the role of iron in erythropoiesis.

2. List the dietary sources of iron, the factors influencing the absorption of iron, and the causes of iron deficiency.

3. Describe the clinical and haematological features of iron deficiency anaemia, and the diagnosis and management of iron deficiency.

4. Describe the clinical and haematological features of anaemia of chronic disease and explain how this is distinguished from iron deficiency.

IRON is mostly present in the body bound to haemoglobin Hb; therefore deficiencies of iron are primarily going to affect the haemoglobin and therefore the blood.

Each haem group is associated with a globin chain.

Erythropoiesis Iron binds to transferrin molecule

Transferrin binds to transferrin receptor on the erythroblasts and passes over the iron molecules.

Transferrin is released back into the circulation

Erythroblasts undergo erythropoiesis (become red blood cell).

Iron acts to increase the production of ferritin, and decrease the production of the transferrin receptor.Sources of Iron include

Meat (haem)

Fish (haem)

Green Vegetables

Cereal, fortifiedIron is absorbed in the duodenum.FACTORS AFFECTING ABSORPTION

- Increased.ACID e.g. orange juice

- DecreasedALKALINE e.g. tea, chapattisHaem is better absorbed than free iron (up to 10% absorption) and its absorption is not adversely affected by other food components. In contrast, non-haem iron (i.e. Fe2+ and Fe3+) from vegetable sources are less well absorbed (1-2% absorption) and may be affected by other dietary factors.

Iron stores: (3-5 grams)

haemoglobin & myoglobin (2-3 grams)

ferritin and haemosiderin (1 gram)

plasma bound protein iron including transferrin (3 milligrams)Causes of iron deficiency

BLOOD LOSS (heavy periods, haemorrhage,) DIET (vegans, vegetarians) INCREASED NEED (pregnancy) MALABSORBTION

Classic iron deficiency:





Serum iron


Ferritin (useful!)




Transferrin saturation LOW

Treatment is generally IRON REPLACEMENT usually by oral route (ferrous sulphate tablets)

Anaemia of chronic disease is where there is no obvious cause apart from that the patient is unwell. It is normally associated with infection, inflammation or malignancy.

Classic anaemia of chronic disease:




LOW or N

Serum iron






Transferrin saturation normal

1. RAISED C-reactive protein

2. RAISED Erythrocyte Sedimentation Rate

3. Acute phase response- INCREASES in

- ferritin


- fibrinogen

- immunoglobulins

You can distinguish between anaemia of chronic disease and iron deficiency by using bone marrow aspirate.

It is caused by cytokines (such as TNF alpha and interleukins) that are released at times of infection, inflammation or malignancy. They prevent the flow of iron into red blood cells which in turn blocks iron utilization by:1. Stopping erythropoietin increase

2. Stopping iron flow out of cells

3. Increasing production of ferritin

4. Increasing death of red cellsHaematology 2 B12 & Folic Acid Deficiency

Anil Chopra1. Describe the role of vitamin B12 and folic acid in haemopoiesis, dietary sources and absorption of these vitamins, causes of deficiency, clinical and haematological features of vitamin B12 and folic acid deficiency and the diagnosis, further investigation and management of these deficiencies

2. Be able to explain that

a. Synthesis of DNA requires both vitamin B12 and folate

b. Integrity of the nervous system requires vitamin B12B12

Required for DNA synthesis

Required for the integrity of the nervous system.

Folic acid

Required for DNA synthesis

Required for Homocystine metabolism

Deficiency affects any cells which are rapidly dividing (bone marrow, epithelia of mouth and gut, embryos, gonads). Also leads to:

Anaemia: weak, tired, short of breath


Glossitis and angular cheilosis

Weight loss, change of bowel habit


Anaemia can either be MACROCYTIC or MEGALOBLASTIC

Macrocytic Anaemia generally defined by an increase in mean cell volume (MCV)This is usually measured by an automated full blood count. It can be caused by B12 or folate deficiency, liver disease, hypothyroidism, alcohol, drugs and haematological disorders.

Megaloblastic Anaemia - abnormal red cell development.

Normal Red Cell Development1) Proerythroblast: large cell with dark blue cytoplasm (high RNA content). It contains condensed chromatin.

2) Basophilic erythroblast: less RNA and more haemoglobin than proerythroblast.

3) Polychromatic Erythroblast: less RNA and more haemoglobin than basophilic erythroblast.

4) Pyknotic erythroblast: less RNA and more haemoglobin than polychromatic erythroblast. This moves out of the bone marrow.

5) Reticulocyte: nucleus is extruded completely and is found in the peripherals.

6) Mature Red blood Cells: formed from maturation of the reticulocytes.

In megaloblasic anaemia, the maturation (disappearance) of the nucleus does not happen at the same time as the development of the cytoplasm. The nucleus or parts of it are therefore visible (these cells are known as megaloblasts). These therefore die in the bone marrow and so red cell production increases to compensate by a process known as incomplete erythropoiesis.

White blood cells are also affected:

Hypersegmented neutrophils (nuclei have many segments)

Giant metamyelocytes (2-3 times their normal size)

Can be defined by high MCV, although cells vary in size (anisocytosis) along with low haemoglobin, and low white blood cell count. Causes include B12 or folate deficiency or drugs.

B12 and Folate Deficiencies

Caused by: inadequate intake

increased demand



premature babies



inadequate absorption

coeliac disease

excessive loss / utilisation

Folate DeficiencyFolate is contained in fresh leafy vegetables and animal products but is destroyed by overcooking, canning or processing. Diagnosis:

Full blood count (folate levels)

Blood film

Take history (look for alcoholism, skin disease, diet, illness, GI infection)

Consequences Megaloblastic, macrocytic anaemia

Neural tube defects in developing foetus

Spina bifida


Increased risk of thrombosis in association with variant enzymes involved in homocysteine metabolism.


Folate replacement

All pregnant women take folic acid 0.4mg prior to conception and for the first 12 weeks

B12 DeficiencyB12 is found in animal products so vegans are at risk. It is mainly caused not by inadequate intake, but by inadequate absorption. Normally, most B12 absorption is done by intrinsic factor which is synthesised in the stomach. B12-IF then binds to ileal receptors.

Therefore low B12 can occur after a gastrectomy, gastric atrophy, or when the body produces antibodies to parietal cells and intrinsic factor. This autoimmune condition (known as Pernicious anaemia has a peak at around 60 years, is familial and increases the risk of stomach cancer in males).

Another main cause of B12 malabsorption is small bowel disease. This can include Crohns or coeliac disease or bowel infections (tapeworm).


Measure vitamin B12 (will be low)

Neuro examination will reveal absent reflexes.

Check levels of B12 intrinsic factor.

Antibodies for coeliac disease

Shillings test

Drink lots of radioactive B12

Measure the excretion of B12 in the urine.

If there is no B12 in the urine repeat the test with intrinsic factor.

ConsequencesNeurological problems

Bilateral peripheral neuropathy (loss of peripheral vision)

Subacute combined degeneration of the cord

Posterior and pyramidal tracts of the spinal cord are degraded

Optic atrophy (retinal tissue destroyed)




Muscle weakness

Difficult walking

Visual impairment

Psychiatric disturbance

Haematology 3 Haemoglobin and Thalassaemia

Anil Chopra

1. Name the key components of haemoglobin

2. Name 3 types of haemoglobin

3. Describe the oxygen dissociation curve

a) state what each axis represents

b) explain the shape

c) name 3 factors which affect it

4. Understand relationship between globin genes and different types of haemoglobin

5. Explain how genetic defects in globin genes lead to thalassaemia

6. Describe clinical and haematolog