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Y2 - BRS - CVR > Anaemia Tutorial > Flashcards

Anaemia Tutorial Flashcards

1
Q

What are the 4 main causes that lead to anaemia?

A

Reduced production of red cells / haemoglobin in the bone marrow

Reduced survival of red cells in the circulation (haemolysis).

Bleeding / blood loss

Pooling of red cells in a very large spleen

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2
Q 
Case Study: 
58F - presenting with:
Tiredness
Lethargy
Breathlessness at rest, which is worse on exertion
ankle swelling at the end of the day

FBC 12 months ago was normal, repeat FBC arranged and it shows:

Hb - 80 g/l
MCV - 70 fl
MCH - 24.5 pg
MCHC - 278
RBC - 3.7 x 10^12
Platelets 550 x 10^9

What do these blood test results show and what is the differential diagnosis for this?

A

Microcytic anaemia (low haemoglobin count)

Issue with RBC production - could be iron deficiency or anaemia of chronic disease

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3
Q

What tests would you conduct next to narrow down the differential diagnosis?

A

Blood test and blood film

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4
Q

What do these test results show?

Low ferritin
Low Serum iron
High Transferrin 
Low transferrin saturation 
No increase HbA2 in Hb electrophoresis

What does this data suggest towards the cause?

A

Iron deficiency

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5
Q

What does the blood film show?

A

Microcytic RBCs?

unsure

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6
Q

What further questions could you ask to figure out what is causing the iron deficiency?

A

Diet - vegetarian or non-vegetarian

GI symptoms e.g. dysphagia, dyspepsia, abdominal pain, change in bowel habit, haematemesis, rectal bleeding, malarna, post-menopausal bleeding

Medications - aspirin, NSAIDs, other steroids

Weight loss

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7
Q

What is haemolysis?

How long does a typical RBC last?

What is anaemia caused by haemolysis?

A

Destruction of RBCs / shortened life span or RBCs

120 days

Haemolytic anaemia - due to G6PD deficiency

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8
Q

Where is haemolytic anaemia common? And why?

A

Africa - protects against malaria

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9
Q

What is a common name for a type of haemolytic anaemia?

Who is it more common in and why?

A

Sickle Cell Anaemia (SCA)

More common in males = recessive disorder

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10
Q

Case Study:
Healthy man develops jaundice
Unconjugated bilirubin high

What does this say about the cause?

A

UNCONJUGATED = haemolysis

Conjugated = liver disease

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11
Q

Blood count shows:
Hb 77g/l
MCV = 108 fl
Reticulocytes = 320 x 10^9

What does the high reticulocyte say?

A

Reticulocyte = baby RBCs

Bone marrow trying to compensate for anaemia

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12
Q

Why is MVC increased?

A

Because reticulocytes are larger than RBCs (I think)

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13
Q

Why is it likely to be haemolysis?

A

Due to the high unconjugated bilirubin

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14
Q

What test would you do next to confirm his diagnosis?

A

Blood film

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15
Q

What does his blood film show?

A

RBC looks normal - normal central palor, normal size

Some RBCs = hemighosts = irregularly contracted cell (=oxidant stress on RBC) = hyperchromatic + irregular membrane (heinz bodies)

Ghost cell

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16
Q

What is a special test to look for heinz bodies?

A

Heinz body test - although can be easily seen on a blood film

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17
Q

How can G6PD deficiency be confirmed?

A

By assay

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18
Q

What advice would be given to the patient to treat this?

A

Avoid oxidant drugs
Avoid broad beans (fava beans)
Avoid naphthalene
Beware haemolysis can result from infection - be mindful getting ill can precipitate a crisis

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19
Q

Case Study:
38F - afro-caribbean, attends rheumatology clinic

Fluctuating multi-system disorder:
Ploy arthritis
Shortness of breath
Facial skin rashes
Hepatitis
Tiredness

What would you do next?

A

Arrange for a blood test

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20
Q

Blood tests show:

RBC - 87
MCV - 104
WBC and platelets - normal
Ferritin - 310 
Bilirubin - 55
B12 and folate - normal

What information does this tell us?

A 
Macrocytic 
Low Hb
High Bilirubin 
B12 and folate normal 
High MCV
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21
Q

She has high LDH, why?

A

Cells are being broken down so intracellular contents are leaking out

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22
Q

What does a high reticulocyte count indicate?

A

Modestly high = RBCs are trying to be replaced by the bone marrow

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23
Q

What does high unconjugated bilirubin suggest?

A

Haemolytic anaemia

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24
Q

How do you work out what type of haemolysis?

A

Do blood film

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25
Q

How do you know if haemolysis is acquired or inherited?

A

Inherited = born with

Env = non-immune or immune mediated

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26
Q

What can the different types of haemolysis be caused by and present as?

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

Immune mediated:
Auto immune
Allo immune (post blood transfusion)

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27
Q

What test can be conducted to figure out whether environmental haemolysis is non-immune or immune?

A

History - she has joint, kidney and history problems = lupus = autoimmune

Suggests immune mediated

Do antibody test = direct antiglobulin test:
Human antibodies (immunoglobulin) bind to the antigens on saline suspended RBCs
Add to the saline suspended blood cells rabbit antibody, these bind to human immunoglobulin - causes cells to clump giving a positive DAT
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28
Q

What are the takeaway points for haemolytic anaemia?

A

Normocytic anaemia with a raised bilirubin consider haemolysis if also:
Elevated Reticulocytes/LDH/unconjugated Bilirubin Blood film

Clinical history and exam may point to acquired or inherited (eg sickle cell)

In acquired haemolysis, DAT positive confirms immune mechanism:
Systemic auto immune disease
Underlying lymphoid cancer (lymphoma)
Idiopathic

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29
Q

10F - jaundice
Appeared quite well but blood tests were done
No evidence of viral hepatitis but liver function tests and blood count and blood film all abnormal

Liver function test showed increased unconjugated bilirubin, normal liver enzymes

How is unconjugated bilirubin interpreted?

A

Pre-hepatic bilirubin - has not yet passed through the liver

30
Q

Her blood count showed Hb98 - slightly low = mild anaemia

What is abnormal on the film?

A

Spherocytes - reduced diameter, no central palor = suggests she has something that causes spherocytosis

31
Q

Suggest a differential diagnosis?

A

Inherited

Haemolytic anaemia

32
Q

Tests show she has hereditary spherocytosis which is due to an inherited defect in the red cell membrane

A

Progressive loss of the RBC membrane - cells get more rigid = rigid spheres

33
Q

Her blood film also shows polychromatic macrocytes, what does this suggest?

A

Blue macrocytic cells = reticulocytes = increased count of reticulocytes
230 x 10^9

Suggests her bone marrow is producing more RBCs than normal - to replace RBCs that are lost

34
Q

Haemolysis VS haemolytic anaemia?

A

Haemolysis = lowered RBC lifespan <120 days

Haemolytic anaemia = cannot compensate for lowered RBC count

35
Q

How do patients with chronic haemolysis get treated?

A

Folic acid - need due to increased DNA synthesis

Splenectomy (if severe) to increase red cell life span - spleen takes out the rigid RBCs (spehrocytes) out of the circulation

36
Q

Patient, now 18, presents with acute upper right abdominal pain and tenderness
Jaundice more marked
High conjugated bilirubin

What is going on?

A

Gallstones at young age due to increased breakdown of Hb to bilirubin
Stone obstructed bile duct = obstructive jaundice
Liver = still able to conjugate bilirubin but it cannot go anywhere

37
Q

62F -

Severe tiredness
Decreased exercise tolerance 
Funny feeling on her feet - walking on cotton wool
Paler skin and yellowish tinge
Depigmentation affecting the face 
Blood test shows
Hb - 45 (v. v. anaemic) = v. v. low 
MCV - 128 = high 
WBC - 3.7 x 10^9 = low
Platelets - 140  x 10^9 = low

What does this information tell you?

A

Issue with bone marrow, all the BCs = low

38
Q

Unconjugated bilirubin = little high
Reticulocytes = lower part of the normal range

What does this information suggest?

A

Unconjugated = haemolytic anaemia

Bone marrow is supposed to compensate for anaemia (reticulocytosis) but this is not happening

39
Q

What does the blood film show?

A

Hypersegmented neutrophils

Very macrocytic RBCs

Poikilocytosis - funny shaped RBCs = tear shapes, ovals, etc.

40
Q

What does the blood film suggest for a differential diagnosis?

A

MDS (myelodysplasia)
B12 deficiency
Folate deficiency
Chemotherapy drugs

41
Q

Why is a blood test required to diagnose for B12 AND folate?

A

B12 and folate both present in the exact same way as they are both required for DNA synthesis

The blood test shows low B12

42
Q

What occurs in bone marrow in megablastic anaemia due to Vitamin B12 deficiency?

A

Erythroblasts - normal and abnormal erythoid precursors

Megablasts = large with nucleocytoplastmic dissociation

So the maturation of the cytoplasm and nucleus is dyssynchronised (not synchronised) = impaired DNA synthesis

43
Q

What are B12 and Folic Acid required for?

A

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
44
Q

How can you become B12 or folate deficient?

A 
B12 deficiency:
Dietary - malnourishment, veganism
Gastric - gastrectomy,
autoimmune (pernicious anaemia)
Bowel - crohn's disease, ileal resection

Folic acid deficiency:
Reduced availability - poor diet, poverty, alcoholism, malabsorption (coeliac disease, jejunal resection)
Increased demand - pregnancy, lactation, increased cell turnover (haemolysis)

45
Q

How can B12 and folate deficiencies be treated?

A

B12 deficiency due to diet = oral supplements
B12 deficiency due to gastric or bowel issues = hydroxocobalamin injections (intramuscular)

Folic acid deficiency = oral supplements

46
Q

What neurological disorders can present due to Vit B12 and folic acid deficiency?

A

Vit B12: dementia, SACD (sub-acute combined degeneration) of spinal cord

Folic acid: developmental neural tube defects

47
Q

Areas of depigmentation suggests?

A

Vitiligo

48
Q

What does a medical history of other autoimmune conditions suggest?

A

Autoimmune - pernicious anaemia

Due to vitiligo which is already an autoimmune condition

49
Q

Summarise megablastic anaemia and its causes:

A

Anaemia due to asynchronous nucleocytoplasmic maturation in the bone marrow

Most common causes = Vit B12 and/or folic acid deficiency

50
Q

Define the terms:

Macrocytic anaemia
Pernicious anaemia
Megaloblastic anaemia

A

Macrocytic anaemia =

Pernicious anaemia = autoimmune

Megaloblastic anaemia = nucleus and cytoplasm maturation in bone marrow not synchronised; B12 or folic acid deficiency

51
Q

Case Study:
45M - severe rheumatoid arthritis
Has taken NSAIDs over time and corticosteroids for chronic inflammation

Anaemic - Hb 85
Hb used to be 115 at previous attendance

MCV = 70 = normal
Reticulocytes = 54 x 10^9 = lower end of normal 
Platelets = 550 x 10^9 = high

What does the FBC suggest?

A

Low reticulocyte for anaemia

High platelet count = due to inflammation

Hb = low

Microcytic anaemia

52
Q

What are common causes for microcytic anaemia?

A

Iron deficiency

53
Q

Patient’s blood test shows:

Hb low 
MCV low
Ferritin high 
Serum iron low 
Transferrin low 
Transferrin saturation normal 
ESR 79 mm/hr

Which of these results are most important and why?

A

Ferritin high
Serum iron low
Transferrin low

Free iron = v. toxic to the body, normally have v.low serum iron

In blood iron is bound to transferrin, in organs iron is bound to ferritin

54
Q

What does the blood film show?

A

Hypochromic, microcytic, RBCs

Rouleaux (aggregations of RBCs)

55
Q

What does the high ferritin count suggest?

What does the low transferrin count suggest?

A

High ferritin = high storage of the iron in the organs

Low transferrin = inappropriately low as it should be raised to allow for iron to be transported around the body where it is required

56
Q

What is the likely diagnosis?

A

Anaemia chronic disease - characteristic findings =
Low / normal transferrin when it should be high whilst you’re anaemic

And typically high ferritin

57
Q

Chronic disease anaemia VS iron deficiency anaemia:

A 
Disease | Anaemia of Chronic Disease | Iron Deficiency Anaemia 
Hb | low | low
MCV | low/normal | low
Ferritin | high | low
Serum iron | low | low
Transferrin | low/normal | high
Transferrin saturation | normal | low
ESR | high | (may be) high
58
Q

What is anaemia of chronic disease?

A

Anaemia in unwell patients with no obvious cause e.g. no bleeding, no haeomlysis, no marrow infiltration, no iron / B12 / folic acid deficiency

Caused by inflammation - e.g. from infections, TB, HIV, autoimmune disorders, rheumatoid arthritis, malignancy etc.

Must treat it which allows anaemia to get better

59
Q

What is iron haomeostatis?

A

Excess iron = potentially toxic to organs esp. heart and liver

No physiological mechanism to remove iron from the blood

Therefore, iron absorption is tightly controlled - regulated by hepcidin (hepcidin blocks absorption and release of storage iron)

60
Q

What happens to hepcidin production when there is increased inflammatory (like in anaemia of chronic disease)?

How does this cause an erythropoeitin production issue eventually leading to anaemia?

A

Hepcidin production is increased

Hepcidin reduced iron absorption, iron transport and iron availability
This decreases EPO (erythropoeitin) production leading to anaemia

61
Q

What are the 3 common causes of reduced red cell survival?

A

Hereditary spherocytosis
Autoimmune haemolytic anaemia
G6DP deficiency

62
Q

What are the 3 common causes of reduced red cell production?

A

Iron deficiency anaemia
Anaemia of chronic disease
Megaloblastic anaemia

63
Q

What is meant by the terms:

Microcytic
Macrocytic
Normocytic

What are each of these normally accompanied by?

A

Microcytic - RBC smaller than normal, usually also hypochromic

Macrocytic - RBC normal, usually also normochromic

Normocytic - RBC larger than normal, usually also normochromic

64
Q

Can anaemia be classified on basis of cell size?

A

Yes

65
Q

What does microcytic anaemia indicate?

A

Generally indicates defect in haem synthesis:

  • Iron deficiency anaemia
  • Anaemia of chronic disease

Or defect in globin synthesis (thalassaemia):

  • Defect in alpha chain synthesis (alpha thalassaemia)
  • Defect in beta chain synthesis (beta thalassaemia)
66
Q

How does iron deficiency anaemia and thalassaemia differ in an FBC?

A 
Condition | Iron deficiency anaemia | Thalassaemia trait
Hb | low | low
MCV | low | low
MCH | low | low
MCHC | low | preserved
RBC | low | high
Ferritin | low | normal
67
Q

How can thalassaemia be distinguised between alpha and beta?

A

Hb electrophoresis:

Alpha = normal
Beta = Hb A2 raised
68
Q

What does macrocytic anaemia indicate?

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)

69
Q

What can lead to haemolysis?

A

Reduced erythrocute function due to:

  • Loss of integrity of membrane e.g. hereditary spherocytosis, autoimmune haemolytic anaemia
  • Change in Hb structure and function e.g. sickle cell anaemia (SCA)
  • Change in cellular metabolism e.g. G6PD deficiency
70
Q

What may cause normocytic anaemia?

A
  1. Recent blood loss e.g. GI haemmorrhage, trauma
  2. Failure of RBC production e.g. early stages of iron deficiency, bone marrow failure or suppression (chemotherapy), bone marrow infiltration (leukaemia)
  3. Pooling of RBCs in the spleen e.g. hypersplenism (liver cirrhosis), splenic sequestration in SCA (sickle cell anaemia)

Y2 - BRS - CVR (21 decks)

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