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Y2 - BRS - CVR > Anaemia Tutorial > Flashcards

Anaemia Tutorial Flashcards

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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
How do you know if haemolysis is acquired or inherited?
Inherited = born with Env = non-immune or immune mediated
26
What can the different types of haemolysis be caused by and present as?
``` Non-immune: Microangiopathic Haemolytic uraemic syndrome Malaria Snake venom Drugs ``` Immune mediated: Auto immune Allo immune (post blood transfusion)
27
What test can be conducted to figure out whether environmental haemolysis is non-immune or immune?
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 ```
28
What are the takeaway points for haemolytic anaemia?
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
29
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?
Pre-hepatic bilirubin - has not yet passed through the liver
30
Her blood count showed Hb98 - slightly low = mild anaemia What is abnormal on the film?
Spherocytes - reduced diameter, no central palor = suggests she has something that causes spherocytosis
31
Suggest a differential diagnosis?
Inherited | Haemolytic anaemia
32
Tests show she has hereditary spherocytosis which is due to an inherited defect in the red cell membrane
Progressive loss of the RBC membrane - cells get more rigid = rigid spheres
33
Her blood film also shows polychromatic macrocytes, what does this suggest?
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
Haemolysis VS haemolytic anaemia?
Haemolysis = lowered RBC lifespan <120 days Haemolytic anaemia = cannot compensate for lowered RBC count
35
How do patients with chronic haemolysis get treated?
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
Patient, now 18, presents with acute upper right abdominal pain and tenderness Jaundice more marked High conjugated bilirubin What is going on?
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
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?
Issue with bone marrow, all the BCs = low
38
Unconjugated bilirubin = little high Reticulocytes = lower part of the normal range What does this information suggest?
Unconjugated = haemolytic anaemia Bone marrow is supposed to compensate for anaemia (reticulocytosis) but this is not happening
39
What does the blood film show?
Hypersegmented neutrophils Very macrocytic RBCs Poikilocytosis - funny shaped RBCs = tear shapes, ovals, etc.
40
What does the blood film suggest for a differential diagnosis?
MDS (myelodysplasia) B12 deficiency Folate deficiency Chemotherapy drugs
41
Why is a blood test required to diagnose for B12 AND folate?
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
What occurs in bone marrow in megablastic anaemia due to Vitamin B12 deficiency?
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
What are B12 and Folic Acid required for?
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
How can you become B12 or folate deficient?
``` 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
How can B12 and folate deficiencies be treated?
B12 deficiency due to diet = oral supplements B12 deficiency due to gastric or bowel issues = hydroxocobalamin injections (intramuscular) Folic acid deficiency = oral supplements
46
What neurological disorders can present due to Vit B12 and folic acid deficiency?
Vit B12: dementia, SACD (sub-acute combined degeneration) of spinal cord Folic acid: developmental neural tube defects
47
Areas of depigmentation suggests?
Vitiligo
48
What does a medical history of other autoimmune conditions suggest?
Autoimmune - pernicious anaemia Due to vitiligo which is already an autoimmune condition
49
Summarise megablastic anaemia and its causes:
Anaemia due to asynchronous nucleocytoplasmic maturation in the bone marrow Most common causes = Vit B12 and/or folic acid deficiency
50
# Define the terms: Macrocytic anaemia Pernicious anaemia Megaloblastic anaemia
Macrocytic anaemia = Pernicious anaemia = autoimmune Megaloblastic anaemia = nucleus and cytoplasm maturation in bone marrow not synchronised; B12 or folic acid deficiency
51
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?
Low reticulocyte for anaemia High platelet count = due to inflammation Hb = low Microcytic anaemia
52
What are common causes for microcytic anaemia?
Iron deficiency
53
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?
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
What does the blood film show?
Hypochromic, microcytic, RBCs | Rouleaux (aggregations of RBCs)
55
What does the high ferritin count suggest? What does the low transferrin count suggest?
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
What is the likely diagnosis?
Anaemia chronic disease - characteristic findings = Low / normal transferrin when it should be high whilst you're anaemic And typically high ferritin
57
Chronic disease anaemia VS iron deficiency anaemia:
``` 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
What is anaemia of chronic disease?
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
What is iron haomeostatis?
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
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?
Hepcidin production is increased Hepcidin reduced iron absorption, iron transport and iron availability This decreases EPO (erythropoeitin) production leading to anaemia
61
What are the 3 common causes of reduced red cell survival?
Hereditary spherocytosis Autoimmune haemolytic anaemia G6DP deficiency
62
What are the 3 common causes of reduced red cell production?
Iron deficiency anaemia Anaemia of chronic disease Megaloblastic anaemia
63
What is meant by the terms: Microcytic Macrocytic Normocytic What are each of these normally accompanied by?
Microcytic - RBC smaller than normal, usually also hypochromic Macrocytic - RBC normal, usually also normochromic Normocytic - RBC larger than normal, usually also normochromic
64
Can anaemia be classified on basis of cell size?
Yes
65
What does microcytic anaemia indicate?
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
How does iron deficiency anaemia and thalassaemia differ in an FBC?
``` 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
How can thalassaemia be distinguised between alpha and beta?
Hb electrophoresis: ``` Alpha = normal Beta = Hb A2 raised ```
68
What does macrocytic anaemia indicate?
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
What can lead to haemolysis?
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
What may cause normocytic anaemia?
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)

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