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Med 2 > Haematology and Anaemia > Flashcards

Haematology and Anaemia Flashcards

1
Q

What is the basic composition of blood?

A

Plasma = 55% - proteins, water, solutes
Buffer layer = 1% = platelets and leukocytes
RBCs = 45% = erythrocytes

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2
Q

What are the key properties of a rbc?

A

Most abundant cell
Biconcave - no nucleus or organelles
7 micrometers
Lifespan of 120 days
Transport O2 in and CO2 out

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3
Q

What is the structure of Haemoglobin?

A

Quarternat structure - 4 subunits - polypeptide chain (2 of which are alpha, 2 of which are beta sub-units) with a haem group containing an Fe2+
Each Fe2+ can bind one O2 or CO2

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4
Q

What are some examples of haemoglobinopathies?

A

Thalassaemia
Sickle Cell Disease

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5
Q

What is the genetics of alpha thalassaemia?

A

Autosomal recessive - chromosome 16.
Defects in alpha chains of Hb molecule

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6
Q

What are the different severities of alpha thalassaemia?

A

Completely asymptomatic = carrier
Moderate anaemia = Haemoglobin H disease
Intra-uterina death (severe foetal anaemia) = alpha thalassaemia major

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7
Q

What is involved in the management of alpha thalassemia?

A

Monitoring
Blood transfusions
Spleectomy
Bone marrow transplantation

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8
Q

What are the general means by which thalassemia leads to anaemia?

A

RBCs are more fragile -> hemolytic anemia
Spleen filtres and removes old cells -> results in splenomegaly.

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9
Q

What are the genetics of beta thalassaemia?

A

Defects in beta globin in Hb - autosomal recessive mutation on chromosome 11.
Abnormal copies (some function) or deletion genes (no function)

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10
Q

What are the different severities of beta thalassaemia?

A
  1. Minor - one abnormal gene and one normal - mild microcytic, monitoring only.
  2. Intermedia - two defective or one defective+one deletion - more sig microlytic anaemia, occasional blood transfusion, iron chelation to prevent overload.
  3. Major - heterozygous deletions - childhood severe anaemia and failure to thrive - regular transfusion, iron chelation, splenectomy
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11
Q

What is a potential curative treatment for beta thalassaemia major?

A

Bone marrow transplant

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12
Q

What are the indirect risks of thalassaemia major?

A

Bone marrow expansion -> risk of fractures and facial deformities

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13
Q

What is the genetics of sickle cell disease?

A

Autosomal recessive conditions affecting the gene for beta-globin on chromosome 11.

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14
Q

How does sickle cell disease commonly lead to anaemia?

A

Sickle-shaped RBCs.
More fragile - prone to hemolytic anaemia
HbS alters shape of rbcs.

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15
Q

How is sickle cell disease diagnosed?

A

Newborn blood spot screening

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16
Q

What are some consequences of the abnormal shaped Hb in sickle cell disease?

A

Abnormal HbS forms strands - causing sickle shaped cells
‘Increased stickiness’ risk of clots
Carriers = protective against malaria (hence more common in Africa, India etc)

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17
Q

What are some common complications of sickle cell disease?

A

Anaemia
Infections (damaged spleen)
CKD
Stroke
Avascular necrosis of joints
Pulmonary HTN
Gallstones (pigment stones)
Priapism.

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18
Q

What is meant by a sickle cell crisis?

A

A spectrum of acute exacerbations (mild to life-threatening).
Triggered by dehydration, infection, stress, cold weather etc.

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19
Q

What are the different types of sickle cell crisis?

A
  1. Vaso-occlusive disease - distal ischaemia, priapism
  2. Splenic sequestration crisis - blood flow blocked in spleen
  3. Aplastic crisis - temporary absence of erythropoiesis (linked to parvovirus B19)
  4. Acute chest syndrome - vessel supplying lungs clogged
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20
Q

What is the general management of sickle cell disease?

A

Specialist MDT approach
Avoid triggers for sickle cell crises e.g dehydration
Antibiotic prophylaxis (pen V)
Hydroxycarbamide stimulates HbF (not sickle)
Crizanlizumab (prevents RBCs sticking to endothelial cells)
Blood transfusions for severe anaemia
Bone marrow transplant may be curative

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21
Q

Where might extra-medullary haematopoiesis occur?

A

Thymus
Liver
Spleen
Lymph nodes
Can occur in foetal development or cancers etc.

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22
Q

What is the basic cell lineage for rbc production?

A
  1. Pluripotent Haematopoietic stem cell
  2. Myeloid stem cells
  3. Megakaryocyte Erythroid Progenitor
  4. (pro-> early-> intermediate-> late) Erythroblast
  5. Reticulocyte (after nuclear exclusion)
  6. Mature RBC (erythrocyte)
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23
Q

At what stage of rbc development is B12 and folate required?

A

During DNA synthesis from MEP to early erythroblast.

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24
Q

At what stage of rbc development is erythropoietin required?

A

From proerythroblast to early erythroblast.

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25
Q

At what stage of rbc development is iron required?

A

From late erythroblast to reticulocyte

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26
Q

What is a reticulocyte?

A

An immature red blood cell without a nucleus, having a granular or reticulated appearance when suitable stained

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27
Q

What is a megaloblast?

A

Large, abnormally developed rbc typical of folic acid of VB12 deficiency anaemia.

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28
Q

Define anaemia
What are the values for this?

A

A low concentration of Hb in the blood
Men = 130-180g/L
Women = 120-165g/L

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29
Q

What are the difference red cell tests in a FBC?
What do they mean?

A

Haemoglobin - amount
Haematocritc - % blood = rbcs
MCV - av size of rbcs
RDW - range of rbc size
RCC - no. RBCs per unit vol of blood
Reticulocyte count - no. immature rbcs.

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30
Q

What can cause an abnormal haemoglobin on blood results?

A

Low = anaemia
High = polycythaemia

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31
Q

What is a complication of a raised haematocrit?

A

Increased blood viscosity = inc risk of thrombo-emobolic disease e.g PE

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32
Q

When in relation to anaemia might a red cell distribution width by useful?

A

Mixed anaemia - MCV deceptively normal but large variation in rbc size (anisocytosis).

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33
Q

What are some potential causes of an abnormal reticulocyte count?

A

Raised - in anaemia (rbcs destroyed in circulation = compensation for this)
Raised - not anemia - effectively compensating so no longer anaemic
Low - may still be anaemia - bone marrow disorder

34
Q

What blood tests are included in haematinics?

A

B12 and folate etc
Nutrients needed for production of rbcs by bone marrow

35
Q

What tests are included in iron studies?
What are these?

A

Serum ferritin = iron storage
Serum iron = Fe3+
Transferrin = transport molecule
Transferrin % saturation = ratio of serum iron:transferring
Total iron-binding capacity

36
Q

What should be remembered when interpreting serum ferritin in blood?

A

Direct correlation with serum iron -> iron storage molecule
Acute phase protein - can also be raised in inflammation, CKD, liver disease, malignancy, CRP is suggested.

37
Q

Why is serum iron not necessarily useful?

A

Only measures direct (ferric) form Fe3+ = small fraction
Shows diurnal variation
Sensitive to recent iron intake.

38
Q

What is important to remember when interpreting transferrin blood results?

A

Iron transport molecule -> increased when low iron (in order to increase TIBC to get iron to where it is needed most)
Negative acute-phase protein (decrease levels in inflammation)

39
Q

How does transferrin % saturation relate to iron deficiency anaemia?

A

Decreases (as less iron available to saturate)
<16% is supportive if initial tests inconclusive.

40
Q

How should total iron-binding capacity be interpreted in iron deficiency anaemia?

A

Tends to increase
Measures the maximum iron that could be bound to all available transferrin is fully saturated -> transferrin increases when deficient.

41
Q

What are the common signs of macrocytic anaemia on a blood film?

A

Macrocytosis (commonly oval shaped with a pale centre)
Hyper-segmented neutrophils

42
Q

What cell is seen on this blood smear?
What does it indicate?

A

Target cells
Iron deficiency anaemia and post-splenectomy

43
Q

What cell type is seen on this blood smear?
What does it indicate?

A

Heinz bodies (look like blister on cell membrane)
Denatured Hb seen in G6PD deficiency and alpha thalassaemia

44
Q

What type of sign is seen in this blood smear?
What does it indicate?

A

Howel-Jolly bodies
Blobs of DNA material seen with non-functioning spleen e.g sickle cell

45
Q

What type of sign is seen in this blood smear?
What does it indicate?

A

Reticulocytes
% goes up during rapid turnover - can indicate haemolysis

46
Q

What is seen in this blood smear?
What is it indicative of?

A

Schistocytes (fragments of RBCs indicative of damage during circulation)

47
Q

What is seen in the blood smear?
What does it indicate?

A

Sideroblasts - immature RBCs with a nucleus surrounded by iron blobs.

48
Q

What are the generic symptoms of anaemia?

A

Tiredness
Shortness of breath
Headaches
Dizziness
Palpitations
Worsening of co-morbidities e.g angina, heart failure, PAD.

49
Q

What symptoms are specific to iron-deficiency anaemia?

A

Pica (abnormal cravings such as soil)
Hair loss

50
Q

What are the generic signs for anaemia?

A

Pale skin
Conjunctival pallor
Tachycardia and raised respiratory rate.

51
Q

What are some specific signs of iron-deficiency anaemia?

A

Kolioncyhia (spoon shaped nails)
Angular chelitis
Atrophic glossitis
Brittle hair and nails

52
Q

What are some signs of CKD assoacited anaemia?

A

Oedema
HTN
Excoriations

53
Q

What is a sign of haemolytic anaemia?

A

Jaundice

54
Q

What is a sign of thalassaemia?

A

Bone deformities

55
Q

What are the key differents causes of a microcytic anaemia?

A

TAILS
T = thalassaemia
A = anaemia of chronic disease
I = iron deficient anaemia
L = lead poisoning
S = sideroblastic anaemia (bone marrow unable to incorporate iron into Hb)

56
Q

What is the most common anaemia of chronic disease?
How is it treated?

A

In CKD - reduced EPO production
Treatment = EPO injections

57
Q

What classification of anaemia is iron deficiency anaemia?

A

Microcytic
Hypochromic (pale cells due to low Hb)

58
Q

What are the common causes of an iron deficiency anaemia?

A

Restrictive diet -> low intake
Reduced absorption -> coeliac disease
Increase blood iron requirements -> pregnancy
Blood loss -> peptic ulcer, bowel cancer, menstruation

59
Q

What are the two different forms of iron?
Where from and where absorbed?

A

Ferrous = Fe2+ = animal sources
Ferric = Fe3+ = vegetarian foods
Both absorbed in duodenum and jejunum

60
Q

What is important for B12 absorption?

A

Requires functional parietal cells producding intrinsic factor
Absorbed in terminal ileum

61
Q

How might iron study results indicate an iron-deficiency?

A

Serum ferritin = low
Total iron binding capacity = raised
Transferring saturation = low

62
Q

How might iron studies indicate an iron overload?

A

Serum ferritin = high
Total iron binding capacity = same
Transferrin saturation = high.

63
Q

What investigations may be prompted in a adult with a new iron-deficiency anaemia?
Without an obvious cause?

A

FIT test
Colonscopy
OGD

64
Q

What is the management for iron deficiency anaemia?

A

Oral iron - rise of Hb ~20g/L in first month - can cause constipation and black stolls
Iron infusion - rapid boost, risk of allergic reaction and anaphylaxis - should be avoided during infection.

65
Q

What are the common causes of normocytic anaemia?

A

AAAHH
Acute blood loss
Anaemia of chronic disease
Aplastic anaemia
Haemolytic anaemia
Hypothyroidism

66
Q

What inherited conditions can cause a haemolytic anaemia?

A

Hereditary spherocytosis
Hereditary elliptocytosis
Thalassaemia
Sickle cell anaemia
G6PD deficiency

67
Q
A
68
Q

What acquired conditions can lead to hemolytic anaemia?

A
  1. Autoimmune (positive direct Coombs test)/alloimune
  2. Paroxsymal nocturnal haemoglobinuria
  3. Microangiopathic haemolytic anaemia
  4. Prosthetic valve-related haemolysis.
69
Q

What prophylatic treatment is required for patients with hyposplenia/asplenia?

A

Vaccination against encapsulated organisms (strep. pneumonia, N.meningitidis and H.influenza)

70
Q

What is the cause of a normoblastic macrocytic anaemia?

A

Alcohol
Reticulocytosis
Hypothyroidism
Liver Disease
Drugs e.g azathioprine

71
Q

What are some common causes of a megaloblastic macrocytic anaemia?

A

Impaired DNA synthesis prevents the cells from dividing normally.
Cells grow into large, abnormal cells.
Caused by B12 +/- folate deficiency.

72
Q

What are the key features of a B12/folate deficiency?

A

Insidious
May not always be anaemia
Severe B12 deficiency - neuropsychological features (optic atrophy,ataxia etc), glossitis, sub-acute degeneration of the spinal cord (lat and post columnar - ataxia, DCML)

73
Q

What are some common causes of a B12 deficiency?

A

Autoimmune (pernicious anaemia)
Malabsorption (distal ileum) - Crohns, coeliac, gastric surgery, atrophic gastritis
Toxins e.g nitrous oxide
Inadequate dietary intake (fish and eggs)

74
Q

What are some common causes of folate deficiency?

A

Inadequate dietary intake
Alcoholism
GI disorder affecting small bowel
Pregnancy
Increased red cell destruction
Exfoliate skin disorders (e.g psoriasis)
Medications (anti-epileptics)

75
Q

What autoantibodies are typically found in pernicious anaemia?

A

Intrinsic factor antibodies
Gastric parietal cells antibodies

76
Q

What is the treatment for pernicious anaemia?

A

IM hydroxycobalamin injections
Maintenance therapy
B12 deficiency must be treated before folic acid deficiency (if also present) or risk of sub-acute combined degeneration of the spinal cord.

77
Q

What are some common investigations for anaemia?

A

Bloods - FBC, renal profile, LFts, reticulocyte, haematinics, iron studies, TFTs
Special - blood film, myeloma screening, Direct Coombs, Fit test
Bone marrow biopsy
Autoantibodies - IF/gastric parietal cell, coeliac disease serology (anti-TTG)
Camera - colonoscopy and OGD.

78
Q

What are some common indications for a blood transfusion?

A

Acute significant blood loss
Symptomatic anaemia
Hb <70g/L (or 80 is cardiovascular/resp disease)
Acute sickle cell crisis

79
Q

What are some immediate complications of a blood tranfusion?

A

Immune:
1. Acute haemolytic transfusion reaction
2. Transfusion-related acute lung injury (TRALI)
3. Anaphylaxis

Non immune:
1. Bacterial infection
2. Transfusion-associated circulatory overload (TACO)

80
Q

What are some delayed complications of a blood transfusion?

A

Immune:
1. delayed haemolytic transfusion reaction
2. Febril non-haemolytic transfusion reaction
3. Post transfusion purpura
4. Graft vs host disease

Non-immune:
viral infections, malaria, prions

81
Q

What blood tests may be elevated in haemolysis?

A

LDH
Bilirubin

82
Q

What blood tests must be done for a blood transfusion?

A

Two group and saves
One cross match
(should also have a coagulation screen)

Med 2 (22 decks)

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