1B anaemia Flashcards

1
Q

How do we interpret an increase in unconjugated bilirubin?

A
  • Increased RBC breakdown
  • Decreased liver function
  • Increased Hb production
  • Biliary obstruction
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2
Q

Describe any abnormalities in this blood film

A

Spherocytes: There are very round cells without the usual central pallor (which reflects the disc shape of a normal red cell).

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3
Q

What is hereditary spherocytosis?

A

Inherited defect in the RBC membrane.

There is disruption of vertical linkages in membrane, usually akyrin/spectrin.

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4
Q

What do we mean by the term ‘haemolysis’ and ‘haemolytic anaemia’?

A
  • Haemolysis: increased destruction of RBCs (reduced RBC survival)
  • Haemolytic anaemia: group of anaemias in which RBC lifespan is reduced (i.e. haemolysis that leads to a reduction in Hb)
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5
Q

How would a patient with haemolytic anaemia be treated?

A
  • Folic acid (increased requirement for erythropoiesis)
  • Splenectomy (if severe) to increase RBC life span
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6
Q

What can increased breakdown of haemoglobin to bilirubin cause?

A
  • Gallstones
  • Can obstruct CBD and cause obstructive jaundice
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7
Q

Compare conjugated and unconjugated bilirubin

A
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8
Q

How does the bone marrow respond to haemolytic anaemia?

A
  • Increased EPO production
  • Leads to reticulocytes
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9
Q

What is DAT (i)?

A

Direct antiglobulin test (i)

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10
Q

What is DAT (ii)?

A

Direct antiglobuin test (ii)

Extended or modified version of the DAT that includes additional testing parameters

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11
Q

What is a differential for DAT positive?

A

Auto-immune Haemolytic Anaemia (AIHA)

  • Idiopathic
  • Associated with disorders of immune system
    • SLE
    • Underlying lymphoid cancers (lymphoma)
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12
Q

What is laboratory evidence of haemolysis?

A
  • LDH raised
  • Unconjugated hyperbilirubinaemia
  • Reduced haptoglobins
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13
Q

Acquired haemolytic anaemia is a result of RBC defect or RBC environment (plasma/vasculature) defect?

A

Environmental

Inherited is a result of RBC defect

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14
Q

What are environmental factors which can damage RBCs?

A

Non-immune
- Microangiopathic
- Haemolytic uraemic syndrome
- Malaria
- Snake venom
- Drugs

Immune mediated (DAT +ve)
- Auto-immune
- Allo-immune (post-blood transfusion)

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15
Q

What blood disorders are spherocytes seen in?

A
  • Hereditary spherocytosis
  • Acquired auto-immune haemolytic anaemia
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16
Q

What do the small arrows show?

A

Irregularly contracted cells

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17
Q

What do the larger arrows show?

A

There is a special test for Heinz bodies but in fact you can see them in a normal blood film

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18
Q

What do irregularly contracted cells, ghost cells and Heinz bodies indicate?

A

Oxidant damage to the red cell. Heinz bodies are precipitated oxidised haemoglobin.

Ghost cells show that there has been intravascular haemolysis

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19
Q

What should the patient be advised to do when confirmed with G6PD deficiency?

A
  • Avoid oxidant drugs
  • Don’t eat broad beans (fava beans)
  • Avoid naphthalene
  • Be aware that haemolysis can result from infection
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20
Q

What is G6PD?

A

An important enzyme in the hexose monophosphate (HMP) shunt, which is tightly coupled to the metabolism of glutathione, which protects red cells from oxidant damage.

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21
Q

Where may oxidants be generated?

A

In the blood stream, e.g. during infection, or maybe exogenous, e.g. drugs, broad beans

22
Q

What factors can haemolysis result from?

A
  • Intrinsic abnormality of the red cells
  • Extrinsic factors acting on normal red cells
23
Q

How can haemolytic anaemia be classified?

A
  • Inherited: result from abnormalities in the cell membrane, the haemoglobin or the enzymes in the red cell
  • Acquired: result from extrinsic factors such as micro-organisms, chemicals or drugs that damage the red cell

Extrinsic factors can interact with red cells that have an intrinsic abnormality

24
Q

Aside from inheritance, acquired, how else can haemolytic anaemia be classified?

A
  • Intravascular: occurs if there is very acute damage to the RBC
  • Extravascular: occurs when defective RBC are removed by the spleen

Often haemolysis is partly intravascular and partly extravascular

25
Q

What should the patient be asked for iron deficiency anaemia?

A
  • Diet: vegetarian/vegan
  • GI symptoms: dysphagia/dyspepsia/abdominal pain/ change in bowel habit/ haematemesis/ rectal bleeding/ melaena
  • Menstrual history/post-menopausal bleeding
  • Weight loss
  • Medication- e.g. aspirin/non-steroidal anti-inflammatory drugs
26
Q

What are some clinical signs of iron deficiency anaemia?

A
  • Koilonychia
  • Glossitis Angular stomatitis
27
Q

What are causes of iron deficiency?

A
  • Increased blood loss
    • Commonest cause in adults
    • Hookworm commonest cause worldwide
    • Menstrual (menorrhagia)
    • Gastrointestinal (often occult)
  • Insufficient iron intake
    • Dietary (veggies)
    • Malabsorption (coeliac disease, H.pylori gastritis)
  • Increased iron requirements
    • physiological (pregnancy, infancy)
28
Q

What would be seen in a blood film from iron deficiency?

A
  • Small cells: microcytosis (low MCV)
  • Pale cells: Hypochromia (low MCHC)
  • Occasional target cells
  • ‘Pencil cells’ (elliptocytes)
29
Q

How does iron deficiency affect iron homeostasis?

A
30
Q

How is iron deficiency treated?

A

Iron replacement therapy e.g. Ferrous Sulphate tablets

31
Q

What does a low MCV mean?

A

Result from decreased Hb synthesis

  • Defect in haem synthesis
    • Iron deficiency
    • Anaemia of chronic disease
  • Defect in globin synthesis
    • Alpha/beta thalassemia
32
Q

What does increased MCV mean?

A
  • Lack of B12 or folate → Megaloblastic anaemia
  • Liver disease and ethanol toxicity
  • Haemolysis → polychromasia indicates that cell is young
    • Bone marrow releases younger cells before they are ready due to lack of RBCs
  • Pregnancy
33
Q

How does MCH and MCHC help differentiate between iron deficiency and thalassemia?

A
34
Q

What is hepcidin?

A

Hepcidin is usually secreted by the liver in response to high iron stores.

Its production is also increased in inflammatory states. This reduces iron supply.

35
Q

What are megaloblasts?

A

Large cells with nucleocytoplasmic dissociation.

Result from impaired DNA synthesis, nuclear maturation and cell division.

Adequate cytoplasmic maturation and cell growth.

36
Q

What causes megaloblastic change in the bone marrow?

A
  • Vitamin B12 and folate deficiency
    • These are required for DNA synthesis
    • Absence leads to severe anaemia which can be fatal
  • Secondary to agents or mutations that impair DNA synthesis
    • Drugs: azathioprine, cytotoxic chemotherapy
    • Folate antagonists: methotrexate
    • BM cancers: myelodysplastic syndrome
37
Q

What is Vit B12 required for?

A
  • DNA synthesis
  • Integrity of the nervous system
38
Q

What is folic acid required for?

A
  • DNA synthesis
  • Homocysteine metabolism
39
Q
A
40
Q
A
41
Q

What are causes of anaemia?

A
  • Reduced RBC survival
    • Hereditary spherocytosis
    • Autoimmune haemolytic anaemia
    • G6PD deficiency
  • Reduced RBC production
    • Iron deficiency anaemia
    • Anaemia of chronic disease
    • Megaloblastic anaemia
42
Q

How is anaemia classified on the basis of size?

A
  • Microcytic – usually also hypochromic
  • Normocytic – usually also normochromic
  • Macrocytic – usually also normochromic
43
Q

What are common causes of a microcytic anaemia?

A
  • Defect in haem synthesis
    • Iron deficiency anaemia
    • Anaemia of chronic disease
  • Defect in globin synthesis (thalassaemia)
    • Defect in α chain synthesis (α thalassaemia)
    • Defect in β chain synthesis (β thalassaemia)
44
Q

What are the mechanisms of normocytic anaemia?

A
  • Recent blood loss (GI haemorrhage, trauma)
  • Failure of production of red cells (early stages of iron deficiency, bone marrow failure or suppression (chemotherapy), bone marrow infiltration (e.g. leukaemia))
  • Pooling of red cells in the spleen (hypersplenism, e.g. liver cirrhosis, splenic sequestration in sickle cell anaemia)
45
Q

What are common causes of macrocytic anaemia?

A
  • Lack of vitamin B12 or folic acid (megaloblastic anaemia)
  • Use of drugs interfering with DNA synthesis
  • Liver disease and ethanol toxicity
  • Haemolytic anaemia (reticulocytes increased )
46
Q

What is the distinction between megaloblastic anaemia and macrocytic anaemia?

A

Megaloblastic anaemia refers to a macrocytic anaemia that is caused by vitamin B12 or folic acid deficiency.

47
Q

This is a blood film from a patient with megaloblastic anaemia. What cells can you see?

A
  • Tear drop cells
  • Hypersegmented neutrophil
  • Oval macrocytes
48
Q

What are features of haemolytic anaemia?

A
  • Otherwise unexplained anaemia, which is normochromic and usually either normocytic or macrocytic
  • Evidence of morphologically abnormal red cells
  • Evidence of increased red cell breakdown
  • Evidence of increased bone marrow activity
49
Q
A
50
Q
A
51
Q

What is anaemia of chronic disease?

A

Anaemia in patients that are ill.

52
Q

What are some causes of anaemia of chronic disease?

A
  • Infections such as TB and HIV
  • Rheumatoid arthritis and other autoimmune disorders
  • Malignancy