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Anaemia Flashcards

1
Q

Define haemolysis

A

Increased destruction of RBCs

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2
Q

What are haemolytic anaemias?

A

Group of anaemias in which red cell lifespan is reduced

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3
Q

How could a patient with haemolytic anaemia (low Hb) be treated?

A

Folic acid - increased requirement for erythropoiesis
Splenectomy (if severe) to increase red cell life span

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4
Q

What does an increase in unconjugated bilirubin indicate?

A

Problem with haemolysis of RBCs, a post-blood transfusion reaction, cirrhosis of the liver

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5
Q

What name is given to RBCs that are very round without the usual central pallor?

A

Spherocytyes

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6
Q

What is hereditary spherocytosis?

A

A disruption of vertical linkages in the red cell membrane causing red blood cells to become more spherical shaped

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7
Q

What do polychromatic macrocytes look like?

A

Larger and more blue than normal red cells

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8
Q

What are the four primary underlying mechanisms of anaemia?

A

reduced production of red cells/haemoglobin by the bone marrow
(b) reduced survival of red cells in the circulation (haemolysis).
(c) loss of blood from the body
(d) pooling of red cells in a very large spleen.

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9
Q

What are the symptoms associated with hereditary sopherocytosis?

A

Increased red cell osmotic fragility
Jaundice
Gall stones

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10
Q

What is seen on the blood film of someone with hereditary spherocytosis?

A

Spherocytes
Polychromatic macrocytes
High reticulocyte count
High unconjugated bilirubin

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11
Q

What test involving water can be done to test for hereditary spherocytosis?

A

Osmotic fragility test - reveals spherocytosis fragility in hypotonic solution

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12
Q

What does an increased unconjugated bilirubin suggest?

A

Pre-hepatic cause of jaundice
Caused by haemolysis

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13
Q

What does an increased conjugated bilirubin suggest?

A

Decreased elimination of bilirubin by hepatocytes

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14
Q

What are the common complications associated with haemolytic anaemia?

A

Gall stones
- increased breakdown of Hb to BR
- can lead to jaundice

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15
Q

How is hereditary spherocytosis treated?

A

Folic acid
Transfusion if severe
Splenectomy if severe but avoid if possible

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16
Q

What is the lab evidence for haemolysis/ haemolytic anaemia?

A

LDH inc
Unconjugated hyperbilirubinaemia
Reduced Haptoglobins
Increased MCV
Reticulocytosis

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17
Q

Acquired haemolytic anaemia is a result of what?

A

A problem in the RBC environment (plasma/ vasculature)

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18
Q

What environmental factors can damage RBCs?

A

•Environmental factors can damage RBCs
•Non-immune
> microangiopathic
> haemolytic uraemic syndrome
> malaria
> snake venom
> drugs
•Immune mediated
> auto immune
> allo immune (post blood transfusion)

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19
Q

Haemolytic anaemia can be categorised into having what 2 causes?

A

Acquired or inherited

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20
Q

Inherited haemolytic anaemia is the result of what?

A

A defect in RBC themselves

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21
Q

Wheat RBC defects can cause inherited haemolytic anaemia?

A

• abnormal cell membrane - eg. Hereditary spherocytosis
• abnormal Hb - eg. sickle cell
• defect in glycolytic pathway - eg. pyruvate kinase deficiency
• defect in enzymes of pentose shunt - eg. G6PD deficiency

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22
Q

How do we confirm wether the mechanism of haemolytic anaemia is immune or not ?

A

DAT: direct antiglobulin test
- autoantibodies to erythrocytes antigens can be detected
- a rabbit antibody to human immunoglobulin is added to the sample
- positive DAT confirms immune mechani

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23
Q

What is autoimmune haemolytic anaemia?

A

Patient develops auto-antibodies against their own RBCs via a Type II hypersensitivity reaction

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24
Q

What causes autoimmune haemolytic anaemia?

A

• Idiopathic
• Associated with disorders of immune system:
> Systemic auto immune disease (SLE)
> Underlying lymphoid cancers (lymphoma)

25
What is the clinical presentation of autoimmune haemolytic anaemia?
Normocytic anaemia with a raised bilirubin • Elevated Reticulocytes/LDH/unconjugated bilirubin • MCV borderline raised • DAT positive Clinical history and exam may point to acquired or inherited (eg sickle cell)
26
Where is a G6PD deficiency most common?
Middle East, Africa, Southeast Asia and Sardinia
27
Give three examples of anaemia caused by reduced red cell production?
Iron deficiency anaemia Anaemia of chronic disease Megaloblastic anaemia (B12 deficiency)
28
Give three examples of an anaemia cause by reduced cell of red cells?
Hereditary spherocytosis Autoimmune haemolytic anaemia G6PD deficiency
29
What is a G6PD deficiency?
G6PD deficiency x-linked recessive disease - increases RBC sensitivity to oxidative stress (G6PD is part of the pentose shunt which usually protects from oxidant damage) - can lead to acute haemolytic anaemia (usually triggered)
30
What is the clinical presentation of a G6PD deficiency?
• signs of haemolytic anaemia > unconjugated hyperbilirubinaemia > reticulocytosis > high MCV • blood film > ghost cells – indicate intravascular haemolysis Heinz bodies
31
What are Heinz bodies and in which anaemia are they most commonly seen?
Oxidised, precipitated Hb embedded in membrane of RBCs Seen in G6PD deficiency Result of oxidant damage
32
How is G6PD managed?
Advice for G6PD deficiency - Avoid oxidant drugs - Don't eat broad beans - Avoid naphthalene - Be aware that haemolysis can result from infection
33
What are the three main causes of iron deficiency anaemia?
Increased blood loss Insufficient iron uptake Increased iron requirements i
34
What can cause insufficient iron intake?
Dietary - vegetarians Malabsorption - coeliac, h.pylori gastritis
35
What are the symptoms associated with iron deficiency anaemia?
- fatigue - weakness - pale skin - shortness of breath - headache - dizziness - koilonychia (spoon nails) - glossitis (inflammation of the tongue)
36
What are the differential diagnosis of anaemia with a low MCV?
Diff. diagnosis of anaemia with low MCV – iron deficiency anaemia, thalassemia, anaemia of chronic disease
37
What is typically seen in the full blood count for iron deficiency anaemia?
Low Hb Low MCV Low MCH and MCHC Low ferritin and serum iron High transferrin No HbA2 increase
38
What is typically seen on the blood film for a patient with iron deficiency anaemia?
Microcytosis Hypochromia Target cells
39
What questions do patients with suspected iron deficiency anaemia need to be asked?
• Diet - vegetarian/vegan • Gastrointestinal 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 (NSAIDs)
40
What investigations are made for someone with weight loss and abdominal pain?
• Investigating for blood in the stool > (Faecal Immunochemical Test, FIT) • Gastrointestinal (GI) investigations > Upper GI endoscopy - oesophagus, stomach, duodenum > Take duodenal biopsy > Colonoscopy • Coeliac antibody testing
41
Outline the pathophysiology of anaemia of chronic disease?
• hepcidin blocks absorption and release of iron stores • hepcidin production is increased in inflammatory states • pro-inflammatory cytokines interfere with production and action of EPO
42
What are the most common causes of anaemia of chronic disease?
Infections - TB and HIV Rheumatoid arthritis and other autoimmune disorders Malignancy Inflammation
43
How does anaemia of chronic disease typically present?
• blood tests: - low Hb, low MCV - low ferritin (low iron) - low transferrin - high ESR (inflammation) • blood film - hypochromia - microcytosis - rouleaux (aggregation due to high ESR)
44
What is a megaloblast?
An abnormally large uncleared red cell precursor with an immature nucleus compared to cytoplasm
45
What is megaloblastic anaemia?
Type of macrocytic anaemia characterised by an elevated number of megaloblasts in the bone marrow
46
What is the underlying mechanism of megaloblastic anaemia?
Failed DNA synthesis leading to asynchronous maturation of nucleus and cytoplasms in RBCs
47
What are the causes of megaloblastic anaemia?
CAUSES • Vitamin B12/Folate deficiency > 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
48
Why does a vitamin B12 deficiency result in anaemia?
Vitamin B12 is required for 1. DNA synthesis 2. Integrity of the nervous system Folic acid is required for 1. DNA Synthesis 2. Homocysteine metabolism
49
Outline the clinical presentation seen in megaloblastic anaemia
Clinical presentation of megaloblastic anaemia • blood test > low Hb, high MCV > reticulocytosis > high LDH > low vitamin B12 and folate • blood film > poikilocytosis > hyper segmented neutrophils • neurological issues • vitiligo
50
What are the 3 mechanisms that cause a vit.B12 deficiency?
Reduced intake Gastric issues Bowel issues
51
What gastric issues can lead to a vitamin B12 deficiency?
Gastrectomy Autoimmune - pernicious anaemia (anti-IF antibodies) H.pylori
52
Hat bowel issues can result in a vit.B12 deficiency?
Crowns disease Ileal resection Tapeworm Coeliac
53
What examples of reduced availability can cause a folate deficiency?
• Dietary  > poverty  > alcoholism  • Malabsorption  > Coeliac disease  > Jejunal resection
54
What examples of increased demand can result in a folate deficiency?
Pregnancy Lactation Increase in cell turnover - haemolysis
55
How are vit.B12 and folate deficiencies treated?
B12 - oral supplements, hydroxocobalmin injections Folate - oral supplements
56
What neurological disorders are associated with megaloblastic anaemia?
• Vitamin B12: > dementia > SACD (sub-acute combined degeneration) of spinal cord • Folic acid: > developmental neural tube defects
57
What are the common causes of microcytic anaemia?
- 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)
58
What are the common causes of macrocytic anaemia?
Common causes of macrocytic anaemia • 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)
59
What are the most common causes of normocytic anaemia?
Common causes of normocytic anaemia • Recent blood loss > Gastrointestinal haemorrhage > Trauma • Failure of production of red cells > Early stages of iron deficiency > Bone marrow failure or suppression (e.g. 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

Y2 CARDIORESP (15 decks)

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