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haem Flashcards

1
Q

What are the criteria smouldering myeloma?

A

paraprotein >30g/l
>10% plasma cells in BM
no related organ or tissue impairment

doesn’t require treatment, monitoring needed

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1
Q

What is MGUS?

A

monoclonal gammopathy of unknown significance
a premalignant condition that makes paraprotein

increases risk of myeloma and lymphoma

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2
Q

What can come before multiple myeloma?

A

MGUS
Smouldering myeloma

all plasma cell dyscrasias

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3
Q

Do you treat MGUS and smouldering myeloma?

A

Not yet
Just monitor

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4
Q

What is the risk of MGUS and smouldering myeloma progressing to multiple myeloma?

A

MGUS: 1%
SM: 20% in first year, then 5%

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5
Q

What is the criteria for MGUS?

A

Paraprotein <30 g/L.
Monoclonal plasma cells in bone marrow <10%.
Absence of myeloma-related organ or tissue impairment

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6
Q

What investigations would be carried out for multiple myeloma?

A

FBC (anaemia or leukopenia in myeloma)
Calcium (raised in myeloma)
ESR (increased in myeloma)
Plasma viscosity (increased in myeloma)
U&E (for renal impairment)
Serum protein electrophoresis (to detect paraprotein)
Serum-free light-chain assay (to detect abnormally abundant light chains)
Urine protein electrophoresis (to detect the Bence-Jones protein)

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7
Q

What are the main presentations in multiple myeloma?

A

C – Calcium (elevated)
R – Renal failure
A – Anaemia
B – Bone lesions and bone pain

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8
Q

What are the symptoms of multiple myeloma?

A

Persistent bone pain and pathological fractures
Unexplained fatigue and weight loss
Fever of unknown origin
Hypercalcaemia
Anaemia
Renal impairment
Dizziness, confusion, blurred vision, headaches, epistaxis, cerebrovascular event

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9
Q

What is myeloma?

A

a type of cancer affecting the plasma cells (differentiated B lymphocytes) in the bone marrow.
Leads to accumulation of malignant plasma cells

proliferation disorder of plasma cells

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10
Q

What is multiple myeloma?

A

myeloma affecting multiple bone marrows in the body

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11
Q

What are some differentials for multiple myeloma?

A

MGUS
Amyloid light-chain (AL) amyloidosis.
Solitary plasmacytoma.
B-cell non-Hodgkin’s lymphoma
Chronic lymphocytic leukaemia

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12
Q

Examples of triplet drug combos for initial therapy in multiple myeloma

A
  • VTD: Bortezomib, thalidomide, and dexamethasone
  • KRD: carfilzomib, lenalidomide and dexamethasone
  • RVD: lenalidomide, bortezomib and dexamethasone
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13
Q

What does allogeneic stem cell transplant mean?

A

stem cells from a healthy donor

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14
Q

What are autologous stem cells?

A

derived from the patient

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15
Q

Treatment for healthy patients, patients younger than 65-70, with multiple myeloma

A

Induction drug therapy
Stem cell transplant

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16
Q

Possible complications of multiple myeloma

A

Infection
Bone pain and fractures
Renal failure
Anaemia
Hypercalcaemia
Peripheral neuropathy
Hyperviscosity syndrome
Venous thromboembolism

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17
Q

What is lymphoma?

A

malignancies of the lymphoid system
disease may arise at any site where lymphoid tissue is present

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18
Q

What is anaemia?

A

haemoglobin <130 g/Lin men aged ≥15 years
<120 g/L in non-pregnant women aged ≥15 years
<110 g/L (11 g/dL) in pregnant women

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19
Q

What can cause a decreased production of RBCs?

A

Iron, folate and B12 deficiencies
Bone marrow failure

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20
Q

What can cause RBC loss?

A

Bleeding
Haemolysis

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21
Q

What is the most common cause of anaemia worldwide?

A

Iron deficiency

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22
Q

What is the aetiology of iron def anaemia?

A

Inadequate iron intake
Impaired iron absorption
Blood loss
Increased need (e.g. growth in children)

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23
Q

What helps to absorb B12?

A

Intrinsic factor
B12 must bind to IF to be absorbed in terminal ileum

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24
Q

How much iron do men and postmenopausal women lose daily?

A

1mg

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25
Q

How much iron do menstruating women lose daily?

A

2mg

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26
Q

Key presentations of iron deficiency anaemia

A

fatigue
dyspnoea on exertion
pica
restless legs syndrome
nail changes

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27
Q

What are the symptoms of iron deficiency anaemia?

A

Fatigue.
Shortness of breath on exertion.
Palpitations.
Sore tongue and taste disturbance.
Mouth ulcers
Changes in the hair/hair loss.
Pale skin and conjuctiva
Pruritus.
Headache.
Tinnitus.
Angina, which can occur if there is pre-existing CHD

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28
Q

What type of anaemia does iron deficiency cause?

A

microcytic hypochromic anaemia
characterised by small and pale red blood cells on blood film.

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29
Q

What would the MCV value be in ID anaemia?

A

less than 80 fL

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30
Q

What investigations would you do for ID anaemia?

A

FBC (Hb and MCV)
Serum iron (low)
Total iron binding capacity (high, means more space for iron to be bound)
Transferrin saturation (low)
Ferritin (low)

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31
Q

What are some risk factors for ID anaemia?

A

pregnancy
vegetarian and vegan diet
menorrhagia
hookworm infestation (via blood loss)
chronic kidney disease
coeliac disease
gastrectomy/achlorhydria (low gastric acid so harder for iron to be absorbed)
NSAID use (causes gastric ulcers)

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32
Q

Differentials for ID anaemia

A

Thalassaemia
sideroblastic anaemia
Anaemia of chronic disease
Lead poisoning

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33
Q

What’s the initial treatment for ID anaemia?

A

daily oral iron replacement therapy

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34
Q

Side effects of iron supplements for IDA

A

Constipation
Black stools
Diarrhoea
Heartburn
Nausea
Abdominal/epigastric pain

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35
Q

Treatment for patients who can’t tolerate oral iron in IDA

A

IV iron therapy

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36
Q

How do you monitor ID anaemia?

A

Retest Hb within 4 weeks of starting treatment
FBC within 2-4 months if responsive to treatment

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37
Q

What are some complications of ID anaemia?

A

Cognitive and behavioural impairment
Impaired muscular performance
High output heart failure in severe anaemia
Preterm delivery (risk if anaemia in first 2 trimesters)

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38
Q

What is microcytic anaemia?

A

anaemia with an MCV of less than 80

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39
Q

Why does microcytic anaemia occur?

A

As there is a lack of haemoglobin, an extra division of RBCs occurs to maintain adequate Hb concentration
This results in smaller and paler (hypochromic) RBCs

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40
Q

What is the most common cause of microcytic anaemia?

A

Iron deficiency anaemia

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41
Q

What is the mean corpuscular volume?

A

average size and volume of a red blood cell
used in classifying anaemia

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42
Q

Which anaemias are microcytic?

A

Iron def
Sideroblastic
Thalassaemia
Anaemia of chronic disease

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43
Q

Which anaemias are normocytic?

A

anaemia of chronic disease/inflammation
haemorrhagic
haemolytic
leukaemias/ other cancers
myeloproliferative

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44
Q

What is the MCV for microcytic anaemias?

A

less than 80fl

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45
Q

What is the MCV for normocytic anaemias?

A

80-95fL

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46
Q

What is the MCV for macrocytic anaemia?

A

above 95 fl

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47
Q

Which deficiencies are megaloblastic?

A

B12
Folate

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48
Q

In macrocytic anaemias, what is the difference between megaloblastic and non-megaloblastic?

A

Megaloblastic has a problem in DNA synthesis and repair, non-meg doesn’t

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49
Q

Which anaemias are non-megaloblastic?

A

chronic alcohol use
liver disease
hypothyroidism
MDS
haemolysis and haemorrhage

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50
Q

What are non-specific symptoms of anaemia?

A

Pallor
Fatigue and weakness
Dyspnea
Headaches
Dizziness

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51
Q

What is the difference in the time taken to develop B12 and folate deficiency?

A

B12 deficiency takes years
Folate deficiency can happen much faster, e.g. weeks

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52
Q

What type of anaemia is B12 deficiency?

A

Macrocytic megaloblastic

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53
Q

What is the aetiology of B12 deficiency?

A
  • Pernicious anaemia
  • Insufficient dietary B12
  • Medications that reduce B12 absorption (e.g. PPIs, metformin, anticonvulsants)
  • Malabsorption in GI tract: e.g. Crohn’s, coeliac
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54
Q

What medications can lead to B12 deficiency?

A

PPIs
H2 receptor antagonists
Metformin
Anti-convulsants

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55
Q

What are the risk factors for B12 deficiency?

A
  • Age >65 years
  • history of gastric surgery (gastrectomy, or bypass for obesity)
  • vegan and vegetarian diet
  • Chronic GI illnesses (e.g., Crohn’s disease or coeliac disease
  • Use of known causative medications (proton-pump inhibitors, H2 receptor antagonists, metformin, anticonvulsants)
  • Pregnancy
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56
Q

What are some differential diagnoses for B12 deficiency?

A

Folate deficiency
Pernicious anaemia
MDS
Peripheral/ diabetic neuropathies
Crohn’s, coeliac
MS
Hypothyroidism
Alcoholic liver disease

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57
Q

What are the key presentations in B12 deficiency?

A

Paraesthesia
Cognitive changes
Visual disturbance
Numbness

neurological symptoms differntiate it from folate deficiency

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58
Q

What is haemolytic anaemia?

A

Reduction in red cell lifespan due to increased red blood cell destruction

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59
Q

Symptoms of B12 deficiency

A

Fatigue and muscle weakness
Neurological symptoms (paraesthesia, numbness)
Oral ulcers
Vision disturbances
Psychological symptoms
Pallor

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60
Q

Why is B12 needed and what does deficiency mean in this case?

A

Required for DNA synthesis and fatty acid synthesis

Co-factor for methylmalonyl-Co-A, methionine synthesis (important in neural function) and DNA synthesis

rapid sphingolipid turnover in myelin sheath means deficiency can cause neurological symptoms

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61
Q

What is a low serum b12 level?

A

<200 picograms/mL

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62
Q

What investigations would you order for b12 deficiency and what would they show?

A

FBC: MCV high, haematocrit low
peripheral blood smear: megalocytes, hypersegmented polymorphonucleated cells
serum vitamin B12: <200 picograms/mL
reticulocyte count: low

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63
Q

Initial management for b12 deficiency

A

IM hydroxocobalamin 3 times weekly for two weeks
(or alternate days until there is no further improvement in neurological symptoms)

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64
Q

Management for b12 deficiency

A

IM hydroxycobalamin injections 3x a week for 2 weeks
Follow up injections of 1mg every 2-3 months

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65
Q

Complications of B12 deficiency

A

Neurological deficits
Haematological deficits
Psychological conditions and cognitive impairment
If during pregnancy: low birth weight and preterm delivery

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66
Q

Difference between b12 and folate deficiency

A

B12 takes years and has neurological symptoms
Folate takes weeks and has no neuro symptoms

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67
Q

What is folate (B9) deficiency?

A

megaloblastic anaemia, with absence of neurological signs.

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68
Q

What foods is folate present in?

A

Green leafy vegetables, legumes, folic acid in fortified cereal-grain products

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69
Q

Who does folate deficiency most commonly affect?

A

Young children
Older adults
Pregnant women

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70
Q

What is the aetiology of folate deficiency?

A

Inadequate dietary intake
Malabsorption
Increased requirement (pregnancy, growth)
Increased loss of folate: chronic dialysis
Medications: anticonvulsants (e.g. phenytoin), sulfasalazine, methotrexate

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71
Q

What medications can cause folate deficiency?

A

anticonvulsants (e.g. phenytoin)
sulfasalazine
methotrexate

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72
Q

How does folate deficiency affect cells?

A

Folate deficiency impairs DNA synthesis and repair, which holds back cell division and leads to apoptosis of haematopoietic cells in the marrow.

The loss of erythropoietic cells causes anaemia

folate is needed for nitrogen base synthesis

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73
Q

What happens to cells in megaloblastic anaemia?

A

Megaloblastic anaemia results from impaired DNA synthesis, preventing the cells from dividing normally.
Rather than dividing, they grow into large, abnormal cells

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74
Q

What are the risk factors for folate deficiency?

A

low dietary folate intake
age >65 years
alcohol-use disorder
pregnancy or lactation
premature infant
intestinal malabsorption disorders
use of certain medications
infantile exclusive intake of goats’ milk (no folate)
congenital defects in folate absorption and metabolism

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75
Q

Symptoms of folate deficiency

A

loss of appetite and weight loss
fatigue
shortness of breath
dizziness
pallor
dyspnea
tachycardia

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76
Q

What would be seen on a peripheral blood smear in folate and b12 deficiency?

A

Macrocytic anaemia and hypersegmented neutrophils

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77
Q

What investigations would you order for folate deficiency?

A

Serum folate (low) and serum b12 (normal)
Peripheral blood smear (Macrocytic anaemia and hypersegmented neutrophils)
FBC (low Hb, elevated MCV)
reticulocyte count (low)

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78
Q

Why is it important to test patients for both b12 and folate deficiency?

A

Underlying B12 deficiency should be ruled out before implementing therapy with folic acid, because folic acid may mask neurological complications of untreated vitamin B12 deficiency

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79
Q

What does a reticulocyte count show?

A

indicates red blood cell production

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80
Q

Differential diagnoses for folate deficiency

A

B12 deficiency
Alcoholic liver disease
Thiamine-responsive megaloblastic anaemia
Hypothyroidism
Drug-induced macrocytosis
MDS

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81
Q

How would you manage folate deficiency?

A

Once B12 deficiency ruled out:
Oral folic acid replacement

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82
Q

How can you prevent folate deficiency in pregnancy?

A

Folic acid supplementation

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83
Q

What are some possible complications of folate deficiency?

A

Foetal neural tube deficits
Haematological deficits
Progression of neuropathy from masked B12 deficiency

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84
Q

How long do folate stores in the body last?

A

4 months

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85
Q

What lab results would you get for anaemia of chronic disease?

A

Low transferrin sats
High ferritin levels
Normal/low TIBC
Low serum iron
Microcytic or normal

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86
Q

What happens in sideroblastic anaemia?

A

Abnormality in haem synthesis pathway
Iron stores normal

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87
Q

What would be seen on a peripheral blood smear for sideroblastic anaemia?

A

basophilic stippling
pappenheimer bodies

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88
Q

What can cause sideroblastic anaemia?

A

Congenital (X-linked)
Exposure to lead
Medications, e.g. isoniazid for TB

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89
Q

Where are the genes for alpha globin found?

A

Chromosome 16

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90
Q

What is alpha-thalassaemia?

A

a group of disorders of Hb synthesis, caused by mutations or deletions in at least one of the four alpha-globin gene

leading to variably impaired alpha-globin chain production, with accumulation of beta-globin chains

symptom severity depends on number of genes affected

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91
Q

What are the different alpha-thalassaemias?

A

1 affected alpha globin gene: silent carrier
2 affected: alpha thalassaemia trait
3 affected: HbH disease
4 affected: Alpha T major, Hb Bart hydrops fetalis syndrome

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92
Q

How does hypoxia occur in alpha thalassaemia?

A

HbH and Hb Bart’s have a high affinity for oxygen so don’t release it to tissues

The hypoxia causes an increase in RBC production and therefore bone marrow, liver and spleen enlargement

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93
Q

Pathophysiology of alpha thalassaemia

A

accumulation of excess unmatched beta-globin chains, which aggregate, causing oxidant and mechanical damage to the affected red cells and leading to their premature destruction

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94
Q

What would be seen on a peripheral blood smear in alpha thalassaemia?

A

Microcytosis, hypochromia, target cells

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95
Q

What investigations would be done for alpha-thalassaemia and what do they show?

A

Hb: normal to low
MCV: low
MCH: low
RBC count: increased
Serum iron and ferritin: normal/ elevated

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96
Q

Differentials for alpha-thalassaemia

A

Iron deficiency anaemia
Beta-thalassaemia
Anaemia of chronic disease
Lead poisoning
Sideroblastic anaemias (SA)
B12 deficiency anaemia and Folate deficiency
Other haemolytic anaemias

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97
Q

How would HbH disease present?

A

Anaemic
very low MCV and MCH
splenomegaly
variable bone changes.

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98
Q

How does alpha-thalassaemia trait (2 genes affected) present?

A

mild anaemia and low red blood cell (RBC) indices

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99
Q

How would severe thalassaemia present?

A

Hepatosplenomegaly
Bony deformities (frontal bossing, prominent facial bones, and dental malocclusion)
Marked pallor
Jaundice.
Exercise intolerance, cardiac flow murmur or HF secondary to severe anaemia

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100
Q

Do silent carriers or alpha-thalassaemia trait require treatment and monitoring?

A

No
Should not be treated with iron therapy unless iron deficiency is proved

HbH should be monitored for complications

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101
Q

What is the outlook for alpha-thalassaemia major?

A

Without intervention, the fetus is subject to severe hypoxia, leading to hydrops fetalis and the associated morbidity and mortality

Infant can survive into childhood if mother receives intrauterine transfusions, then child has lifelong transfusions

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102
Q

What is beta thalassaemia?

A

Beta-thalassaemia is an inherited blood disorder caused by mutations of the beta-globin gene that results in ineffective erythropoiesis

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103
Q

Where is the beta-globin gene located?

A

Chromosome 11

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104
Q

What is HbA?

A

Adult haemoglobin
2 alpha 2 beta chains

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105
Q

What is HbF?

A

Foetal haemoglobin

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106
Q

Why does Beta-thalassaemia major not present until the first 3-6months of life?

A

HbF still present until this point
HbF can also use up some of the free alpha chains

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107
Q

What is the pathophysiology of beta-thalassaemia?

(haemolysis and hypoxia)

A

Free alpha chains accumulate within RBCs, damaging RBC membrane.

Causes haemolysis in bone marrow or RBC to be destroyed by macrophages in spleen.
Haemolysis causes Hb to spill into plasma, Haem is recycled into iron and unconjugated bilirubin = jaundice and secondary haemochromatosis

Haemolysis leads to hypoxia as fewer RBCs.
Hypoxia signals BM, liver and spleen to increase RBC production, causing BM containing bones (in skull and face), liver and spleen to all enlarge

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108
Q

What is the pathophysiology behind Hb Bart’s Hydrops Fetalis?

A

gamma chains form tetramers in absence of alpha chains
Hb Bart’s has very high affinity for oxygen.
Tissues get no oxygen leading to high output cardiac failure, splenomegaly and oedema across body.
Incompatible with life

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109
Q

What are the different types of beta-thalassaemia?

A

1 mutated beta globin gene: B-T minor (B+) or (B0), asymptomatic
2 mutated beta globin genes code for reduced synthesis (B++): B-T intermedia
2 mutations where no beta globin is produced (B00): B-T major

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110
Q

Classification of B-T minor (BT trait)

A

Slightly anaemic
low MCV and MCH
clinically asymptomatic.

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111
Q

Classification of B-T intermedia

A

-/βo or β+/β+)
high HbF, variable.
Anaemic
very low MCV and MCH
splenomegaly
variable bone changes
variable transfusion dependency

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112
Q

Classification of B-T major

A

(genotype -o/-o)
HbF >90% (untransfused)
Severe haemolytic anaemia
very low MCV and MCH
hepatosplenomegaly
chronic transfusion dependency

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113
Q

What would a peripheral blood smear show for beta-thalassaemia?

A

microcytic red cells
tear drops
microspherocytes
target cells
some fragments
large number of nucleated red cells

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114
Q

What investigations would you do for beta-thalassaemia?

A
  • Peripheral blood smear: microcytic red cells, tear drops, target cells
  • FBC: microcytic anaemia, all blood counts may be lower with increasing splenomegaly
  • LFTs in intermedia and major: elevated total and unconjugated bilirubin
  • Reticulocyte count: elevated
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115
Q

Differentials for beta-thalassaemia

A

Congenital dyserythropoietic anaemia (CDA)
Pyruvate kinase (PK) deficiency
Mild iron deficiency anaemia
Alpha-gene mutations
Haemolytic anaemia
Anaemia of chronic disease

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116
Q

How would you manage thalassaemia?

A

Mild and asymptomatic don’t tend to require treatment. Avoid unnecessary iron supplementation to avoid iron overload
In very severe cases, consider RBC transfusion

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117
Q

Complications of thalassaemia

A

Iron overload
Growth delays (alpha)
Gallstones
Splenomegaly
Leg ulcers
MSK complications (beta)
Gout (beta)
Transfusion related complications

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118
Q

Prognosis for beta-thalassaemia

A

Beta-thalassaemia trait: normal
Beta-thalassaemia intermedia: cosmetic changes, variable iron overload
B-t major: fatal within a few years if untreated, transfusions can greatly increase quality of life and expectancy

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119
Q

What is the pathophysiology of multiple myeloma?

A

Uncontrolled replication of plasma cells and secretion of antibodies

This produces diffuse bone marrow infiltration causing bone destruction and bone marrow failure.
There is also overproduction of a monoclonal antibody (‘paraprotein’) by the malignant plasma cells, detectable in serum and/or urine

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120
Q

What is the normal physiology of B cell differentiation?

A

B cells originate in bone marrow from haematopoietic stem cells
Migrate to lymphoid tissues
Activated by CD4 T cells and develop into plasma cells in the bone marrow
Plasma cells produce large quantities of antibodies

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121
Q

Why does hypercalcaemia develop in multiple myeloma?

A

Increase cytokine secretion (RANK-L) causes increased osteoclast activity
More calcium is released

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122
Q

Why does anaemia occur in multiple myeloma?

A

The cancerous plasma cells invade the bone marrow (bone marrow infiltration)
Suppression of the other blood cell lines, leading to anaemia (low haemoglobin), leukopenia (low white blood cells) and thrombocytopenia (low platelets).

Anaemia in myeloma is normocytic (normal size) and normochromic (normal colour)

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123
Q

What are the 4 types of leukaemia?

A

Acute myeloid leukaemia (rapidly progressing cancer of the myeloid cell line)
Acute lymphoblastic leukaemia (rapidly progressing cancer of the lymphoid cell line)
Chronic myeloid leukaemia (slowly progressing cancer of the myeloid cell line)
Chronic lymphocytic leukaemia (slowly progressing cancer of the lymphoid cell line)

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124
Q

Pathophysiology of leukaemia

A

A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white blood cell.

The excessive production of a single type of cell can suppress the other cell lines, causing the underproduction of different cell types. This can result in pancytopenia

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125
Q

Who does AML tend to affect?

A

more common in older adults (65+)
slightly more common in men

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126
Q

What is acute myeloid leukaemia?

A

haematological malignancy caused by clonal expansion of myeloid blasts in the bone marrow

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127
Q

What is the pathophysiology of AML?

A

genetic abnormalities in haematopoietic precursor cells result in the accumulation of myeloid blasts unable to differentiate into mature neutrophils, RBCs or platelets.
This can lead to bone marrow failure (manifest as anaemia, neutropenia, and/or thrombocytopenia)

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128
Q

Risk factors for AML

A

Exposure to radiation, benzene, or alkylating agents
Chromosomal rearrangements such as t(15;17)(q22;q12)
Chromosomal abnormalities: Down syndrome
Age over 65
Inherited genetic conditions: Bloom’s syndrome
Myelodysplastic syndromes

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129
Q

Signs and symptoms of AML

A

Pallor
Petechiae
Fatigue
Loss of appetite + Weight loss
Fever/ infection
Dizziness
Palpitations
Dyspnoea
Bruising and mucosal bleeding: due to thrombocytopaenia
Pain and tenderness in the bones
Hepatosplenomegaly
Lymphadenopathy (enlarged lymph nodes)

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130
Q

What are the most common sites of infiltration in AML?

A

liver, spleen and gums

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131
Q

What would an FBC show in AML?

A

Anaemia, neutropenia, and/or thrombocytopenia
WBC may be elevated

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132
Q

What would be seen on a peripheral blood smear for AML?

A

Blast cells
presence of Auer rods

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133
Q

What is the diagnositc test for AML?

A

Bone marrow aspiration: ≥20% myeloblasts

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134
Q

What investigations should be done for AML and what would they show?

A

FBC: anaemia, neutropenia, and/or thrombocytopenia, WBC may be elevated despite neutropenia
Clotting screen: DIC
Peripheral blood smear: presence of Auer rods
Bone marrow aspiration: ≥20% myeloblasts
Lactate dehydrogenase

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135
Q

Differential diagnoses for AML

A

ALL
Biphenotypic leukaemia
MDS
Aplastic anaemia
Myelofibrosis (different blood film)
B12 deficiency

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136
Q

Management of AML

A

multi-agent, dose-intense chemotherapy

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137
Q

Complications of AML

A

Pancytopenia
Leukostasis
Tumour lysis syndrome
Neutropenia

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138
Q

Poor prognostic factors for AML

A

> 60 years
20% blasts after first course of chemo
cytogenetics: deletions of chromosome 5 or 7

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139
Q

What is acute lymphoblastic leukaemia?

A

a malignant clonal disease that develops when a lymphoid progenitor cell becomes genetically altered and undergoes uncontrolled proliferation

majority affect B cells but can also affect T

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140
Q

Who does ALL normally affect?

A

Can occur at any age but most common in children
Peak incidence ages 1-4

most common childhood malignancy

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141
Q

Risk factors for ALL

A

Children less than 5 years of age
Family history of ALL
history of malignancy
treatment with chemotherapy
exposure to radiation
smoking
folate metabolism polymorphisms

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142
Q

What factors can contribute to the development of ALL?

A
  • Genetic
  • Genetic disorders: Down, Klinefelter, Bloom
  • Environmental: including radiation exposure and smoking
  • Viral infections
  • History of malignancy
  • Treatment with chemotherapy
  • Poor maternal diet
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143
Q

What are the chromosomal abnormalities for ALL?

A
  • t(12;21) is the most common cytogenetic abnormality in children.
  • In adults, the Philadelphia chromosome is the most common cytogenetic abnormality and describes the translocation t(9;22)
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144
Q

What does a blood film for ID anaemia show?

A

microcytic, hypochromic RBCs
variation in shape and size

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145
Q

When does anaemia of chronic disease occur?

A

in chronic inflammatory diseases, e.g. Crohn’s, SLE, RA

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146
Q

Why does anaemia of chronic disease happen?

A

decreased release of iron from bone marrow to developing erythroblasts
inadequate erythropoietin response to anaemia
decreased RBC survival

147
Q

What is the diagnostic feature of sideroblastic anaemia?

A

Ring sideroblasts

148
Q

What investigation findings would you expect for ID anaemia?

A

Serum iron: low
TIBC: elevated
serum ferritin: low
FBC: low Hb, low MCV
Transferrin saturation: decreased

149
Q

What is total iron binding capacity?

A

indirect measure of the amount of iron that transferrin will bind

150
Q

What are haemolytic anaemias?

A

Caused by increased destruction of red cells

151
Q

What can cause haemolytic anaemia?

A

Hereditary: sickle cell, thalassaemia, hereditary spherocytosis
Malaria
Metabolic: G6PDH deficiency
Autoimmune

152
Q

What is sickle cell anaemia caused by?

A

An autosomal-recessive single gene defect in the beta chain of haemoglobin
Results in production of sickle cell haemoglobin (HbS)

153
Q

What is sickle cell trait?

A

Heterozygous
HbAS

Homozygous is HbSS and anaemia

154
Q

What can sickling cause?

A
  • Shortened RBC survival
  • Impaired passage of cells through microcirculation (leading to obstruction and infarction)
155
Q

What is the mutation in sickle cell?

A

single base of adenine to thymine
Causes a subsitition of valine replacing glutamic acid

156
Q

In sickle cell, what can precipitate a vaso-occlusive episode?

A

acidosis
dehydration
cold temperatures
extreme exercise + stress
hypoxia
infections

157
Q

How do cells sickle?

A

Deoxygenated HbS molecules are insoluble and polymerize.
Flexibility decreases and cells sickle.
Irreversible, dehydrated and dense, can’t revert shape by oxygenating
These cells are also prone to haemolysis, contributing to anaemia

158
Q

Where is sickle cell anaemia most prevelant?

A

sub-saharan africa + western africa
endemic malaria areas, as protective

159
Q

When can symptoms of sickle cell begin?

A

3-6 months of age when HbF levels start to fall

160
Q

Symptoms of sickle cell anaemia

A

Pallor
Jaundice
Lethargy
Dactylitis
Persistent pain in skeleton, chest and abdo

161
Q

What is the most common sickle cell crisis?

A

vaso-occlusive

162
Q

What is vaso-occlusive crisis in sickle cell and how does it present?

A
  • caused by the sickle-shaped RBCs clogging capillaries, causing distal ischaemia.
  • It typically presents with pain and swelling in the hands or feet but can affect the chest, back, or other body areas.
  • can be associated with fever
163
Q

What is acute chest syndrome in sickle cell?

A
  • vessels supplying the lungs become clogged with RBCs
  • presents with fever, shortness of breath, chest pain, cough and hypoxia
  • triggered by vaso-occlusive crisis, fat embolism or infection

CXR shows pulmonary infiltrates

164
Q

What is splenic sequestration?

sickle cell

A

An acute painful enlargement of the spleen produced by vaso-occlusion
There is pooling of RBCs and can have hypovolaemia
Can lead to splenic infarction

165
Q

What are non-haemolytic normocytic anaemias?

A

CKD
Aplastic anaemia

166
Q

What is bone marrow aplasia?

sickle cell

A

Temporary absence of the creation of new RBCs in bone marrow
Most commonly after parovirus B19 infection
No reticulocytes in peripheral blood because of failure of erythropoiesis in marrow
Can lead to aplastic anaemia

166
Q

What is aplastic anaemia?

A

occurs when your bone marrow doesn’t make enough red and white blood cells, and platelets

167
Q

In sickle cell anaemia, which crisis is usually precipiated by a parovirus B19 infection?

A

Bone marrow aplasia

168
Q

In sickle cell, which crisis is characterised by pulmonary infiltrate on a CXR?

A

Acute chest syndrome

169
Q

How is sickle cell screened for?

A

Heel-prick in newborns
Carrier screening in parents

170
Q

What do Howell-Jolly bodies on a blood film indicate?

A

Splenic dysfunction

171
Q

What is seen on a peripheral blood smear for sickle cell?

A

Sickle shaped cells
Howell-Jolly bodies
Nucelated RBCs

172
Q

What is seen on a blood smear for HbSC disease?

A

Oat cells
Target cells

173
Q

What investigation is used to confirm sickle cell and what does it show?

A

Haemoglobin electrophoresis
no HbA, 80-95% HbS and 2-20% HbF

174
Q

What investigations would you do for sickle cell?

A
  • FBC and reticulocyte count: normocytic anaemia, elevated reticulocytes (except in aplasia)
  • Peripheral blood smear: Sickle-shaped cells, Howell-Jolly bodies, presence of nucleated RBCs
  • Haemoglobin electrophoresis: confirms diagnosis no HbA, 80-95% HbS and 2-20% HbF
  • Haemoglobin solubility: ≥10% to 15% HbS
175
Q

What are the differentials of sickle cell disease?

A

Gout
Connective tissue disorders
Osteomyelitis
Septic arthritis
ID anaemia
Avascular necrosis

176
Q

What is the management for sickle cell?

A

Avoid precipitating factors
Hydroxycarbamide
Blood transfusions
Pain relief

177
Q

How does hydroxycarbamide work for management of sickle cell?

A

Stimulating the production of fetal haemoglobin (HbF)
Reduces the frequency of vaso-occlusive crises, improves anaemia and decreases frequency of painful episodes

178
Q

Long term problems in sickel cell

A
  • Decreased growth
  • Bone issues as common site of vaso-occlusive episodes (avascular necrosis of hip and shoulder)
  • Infections
  • Leg ulcers
  • Cardiac problems: MI from thrombosis, iron overload
  • Neuro complications: TIAs, infarction, haemorrhage
  • Priapism: painful erection
  • Hepatomegaly and liver dysfunction
179
Q

What are the 5 types of malaria?

A

Plasmodium falciparum (the most common and severe form)
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi

180
Q

What is malaria?

A

a parasitic infection caused by protozoa of the genus Plasmodium

181
Q

What is the most life-threatening form of malaria?

A

Plasmodium falciparum

182
Q

What should be a key point to suspect malaria?

A

fever with a travel history

183
Q

What is the life cycle in malaria?

A
  • Mosquito bites infected individual and ingests gametocyte
  • Gametocytes reproduce inside mosquito and produce sporozoites
  • Sporozoites in salivary gland of mosquito
  • Mosquito bites new person and injects sporozoites into patient
  • Infection reaches patients liver and matures into schizont
  • Schizont in liver ruptures and enters blood stream as immature trophozoite which becomes a schizont (cyclic)
  • This rupture cycle can cause cyclical fever and haemolytic anaemia
184
Q

What is complicated malaria?

A

Infection complicated by severe organ dysfunction
e.g. cerebral malaria, ARDS, renal failure, sepsis, anaemia

185
Q

What are some complications of anaemia?

A

Cerebral malaria
Shock
ARDS
Renal failure
Bleeding

186
Q

How can malaria cause renal failure?

A

Can be caused by vascular occlusion, dehydration and hypotension, haemolysis and haemoglobinuria

187
Q

What makes p.falciparum malaria more severe?

A
  • Causes RBCs to adhere to endothelium and each other – causing obstruction in circulation
  • Vascular occlusion can cause cerebral malaria (drowsiness, seizures, coma), ARDS, renal failure
188
Q

What issue can p.ovale and vivax cause in malaria and how do you treat them?

A

P.ovale and vivax can form hypnozoites in the liver and stay dormant for years, causing relapse.

Treated with oral antimalarials, primiquine to eliminate

189
Q

How is malaria transmitted?

A

bite of infected female Anopheles mosquito

190
Q

What are the risk factors for malaria?

A

travel to endemic area
inadequate/ absent chemoprophylaxis
insecticide-treated bed net not used in endemic area

191
Q

What are the risk factors for developing a severe disease with malaria?

A
  • Pregnancy
  • Under 5 years
  • Older age
  • Immunocompromised
  • Low host immunity
192
Q

What tests should be run for malaria

A

Blood films: parasites can be seen
FBC, U&Es

193
Q

Symptoms of malaria

A

FEVER
Chills
Headache
Myalgia
Diarrhoea

194
Q

How is complicated malaria treated?

A

IV artesunate

195
Q

How is uncomplicated malaria treated?

A

Oral antimalarials, e.g. Artemether with lumefantrine

196
Q

How is malaria prevented?

nothing works 100%

A

Chemoprophylaxis for travellers
Using mosquito nets and sprays

197
Q

Example of a variation of AML

A

Acute promyelocytic leukaemia

198
Q

What does the mutation in ALL cause?

A
  • precursors lose ability to differentiate
  • Uncontrolled blast cell division, taking up space and nutrition
    This causes cytopaenias like anaemia, thrombocytopenia, and leukopenia.
199
Q

What can happen to some of the uncontrolled blast cells in ALL?

A

Enter into blood and migrate to other organs, e.g. liver and spleen
pre-t cells in T cell ALL can migrate to thymus and lymph node causing these to enlarge

200
Q

Symptoms of ALL

A

Fever
Bone pain
Abdominal fullness (from hepatosplenomegaly)
Lethargy
Infection
Headache (CNS involvement)

201
Q

Signs of ALL

A

lymphadenopathy
hepatosplenomegaly
pallor, ecchymoses, or petechia
testicular enlargement
CN palsies

202
Q

What would be seen on a blood film for ALL?

A

Coarse chromatin
Lymphoblasts
Glycogen granules in cytoplasm

203
Q

What investigations would be carried out for ALL?

A

FBC: anaemia, leukocytosis, neutropenia, thrombocytopenia
Peripheral blood smear
Bone marrow aspiration and trephine biopsy: ≥ 20% lymphoblasts is diagnostic
**Cytogenic analysis **to detect chromosomal abnormalities
Immunophenotyping

204
Q

What are the different types of ALL?

A

common ALL (75%), CD10 present, pre-B phenotype
T-cell ALL (20%)
B-cell ALL (5%)

205
Q

What are some differentials for ALL?

A

AML
ITP
Other cancers
Aplastic anaemia

206
Q

What is the general management for ALL?

A

multi-agent dose-intense chemotherapy regimens in three treatment phases: induction, consolidation, and maintenance

Allogeneic SCT (from a matched donor) is recommended for patients with high-risk disease

207
Q

What are some complications of ALL?

A

Pancytopenia
Infection
Tumour lysis syndrome
Neutropenia

208
Q

What are the poor prognostic factors for ALL?

A
  • Age less than 1 year or older than 10
  • WBC >30 × 10⁹/L on presentation
  • failure to achieve a complete remission within 4 weeks of treatment
  • cytogenetic abnormalities, e.g. t(9;22)
  • Presence of extramedullary disease, e.g. CNS involvement
209
Q

What is tumour lysis syndrome?

A

an oncological emergency caused by the rapid breakdown of cancer cells and the subsequent release of large amounts of intracellular content into the bloodstream

complication of chemo

210
Q

What does tumour lysis syndrome result in?

A

High uric acid
High potassium (hyperkalaemia)
High phosphate
Low calcium (as a result of high phosphate)

211
Q

What is chronic myeloid leukaemia?

A

involves the proliferation of partially mature myeloid cells, in particular granulocytes, within the bone marrow and blood

212
Q

What is the pathophysiology of CML?

genetics

A

CML is associated with the Philadelphia chromosome 22.
Translocation of chromosomes 9 and 22: t(9;22).
BCR from 22 is fused to ABL from 9, forming a BCR-ABL 1 proteins.
BCR::ABL1 is a constitutively active tyrosine kinase causing myeloid cells to continue dividing and become malignant

213
Q

How can CML progress to AML?

A

As the CML cells divide quicker than they should, there’s a high chance that further genetic mutations can happen

CML might progress and accelerate into a more serious acute leukaemia which is called a blast crisis

Can include the formation of a trisomy on chromosome number 8, or the doubling of the Philadelphia chromosome (22)

214
Q

What age group does CML tend to affect?

A

Elderly
65+

215
Q

What is the 3 phases of CML?

A
  • Chronic phase
  • Accelerated phase
  • Blast phase
216
Q

What is the chronic phase of CML?

A

often asymptomatic, patients are diagnosed after an incidental finding of a raised white cell count.
can last several years before progressing

217
Q

What is the blast phase of CML?

A

follows the accelerated phase and involves an even higher proportion (over 20%) of blast cells in the blood.
Has severe symptoms and pancytopenia and is often fatal

218
Q

What is the acceleratead phase of CML?

A

occurs when the abnormal blast cells take up a high proportion (10-20%) of the bone marrow and blood cells. Patients are more symptomatic and develop anaemia, thrombocytopenia and immunodeficiency

219
Q

What are the risk factors for CML?

A

age 65 to 74 years (STRONG)
ionising radiation exposure
male sex

220
Q

Symptoms of CML

A

SOB
Bleeding
Weight loss
Fever and sweating

221
Q

Signs of CML

A

Pallor
Hepatosplenomegaly
Anaemia

222
Q

What investigations should be carried out for CML?

A

FBC: elevated WBC count, anaemia
Complete metabolic profile
Peripheral blood smear: an increase in all stages of maturing granulocytes
Bone marrow biopsy: myeloblast infiltration in the bone marrow
Cytogenetic studies: Ph+ t(9,22)

223
Q

What is the management for chronic phase CML?

A

tyrosine-kinase inhibitors, e.g. imatinib (a first gen)

second gen TKIs can be used if imatinib not suitable

224
Q

What is the management for the blast phase of CML?

A

TKI therapy combined with induction chemotherapy + stem cell transplant

225
Q

Differentials of CML

A

Ph+ ALL
Chronic myelomonocytic leukaemia

226
Q

What is the most common form of leukaemia in adults?

227
Q

What is chronic lymphocytic leukaemia?

A

An indolent lymphoproliferative disorder in which monoclonal B lymphocytes (>5 x 10⁹/L ) are predominantly found in peripheral blood

228
Q

Epidemiology of CLL

A

Most common adult leukaemia
median age at diagnosis is 70 years
more common in men than women

229
Q

Whats the difference between acute and chronic leukaemias?

A

Cells partially mature in chronic
Cells don’t mature in acute

230
Q

How does CLL impact the lymph system?

A

CLL cells can infiltrate the lymphatic system and haematopoietic organs such as liver, spleen, and bone marrow.
Can present with lymphadenopathy, hepatosplenomegaly, and bone marrow suppression.
Recurrent infections can occur because CLL cells are immunologically dysfunctional.

231
Q

Pathophysiology of CLL

A

The B cells interfere with receptors and tyrosine kinases.
This causes them to only partially mature and die slower than they divide, causing a build up.
Premature cells also express proteins in their surface, such as CD5, CD23
CLL cells can then infiltrate the immune system

232
Q

How can CLL cause autoimmune haemolytic anaemia?

A

CLL cells may also be involved in initiating autoantibody production by normal B cells
leading to autoimmune reactions such as autoimmune haemolytic anaemia

233
Q

Signs of CLL

A

Lymphadenopathy
Splenomegaly
Hepatomegaly

234
Q

Symptoms of CLL

A

Fatigue
SOB
Easier bleeding
Infections

235
Q

What does a blood film show for CLL?

A

Smudge cells

236
Q

What investigations should be done for CLL?

A

WBC: elevated
Blood film: smudge cells (aka smear cells)
Immunophenotype: CD5, CD19, CD20, CD23
FBC (Hb and platelets): anaemia and thrombocytopenia

237
Q

Differential of CLL

A

Leukemic phase of lymphoma

238
Q

Which gene mutations in CLL are associated with a much poorer prognosis and rapid disease?

A

TP53
NOTCH1
del 17p and 11q

239
Q

Treatment example for CLL

A

Immunotherapy with anti-CD20 monoclonal antibodies (e.g., rituximab, ofatumumab, obinutuzumab) improves survival and remission rates, particularly when combined with chemotherapy

240
Q

What targeted therapies can be used in CLL?

A

Tyrosine kinase (BTK) inhibitors (e.g., ibrutinib)
anti-CD20 Monoclonal antibodies (e.g., rituximab, which targets B-cells)

241
Q

What are some complications of CLL?

A

tumour lysis syndrome (TLS)
hypogammaglobulinaemia
autoimmune haemolytic anaemia
immune thrombocytopenic purpura
second malignancies

242
Q

What is Hodgkin’s Lymphoma?

A

a malignant proliferation of lymphocytes (mature B cells) characterised by the presence of the Reed-Sternberg cell

243
Q

The prescence of which cell characterises Hodgkin’s lymphoma?

A

Reed-sternberg cells

244
Q

Epidemiology of Hodgkin’s lymphoma

A

Peak incidence 20-34 years
Bimodal distribution: incidence peaks around age 20-30 then later again above age 55

245
Q

Which form of Hodgkin’a lymphoma has the worst prognosis?

A

Lymphocyte depleted

246
Q

What are the different classifications of hodgkin’s lymphoma?

A

Classic: nodular sclerosing (70%), mixed cellularity (20%), lymphocyte rich (5%), lymphocyte depleted (rare)
Nodular lymphocyte-predominant

247
Q

What is nodular lymphocyte predominant HL characterised by?

A

Popcorn cells

248
Q

What is the basic pathology of Hodgkin’s lymphoma?

A

B cell malignancy
THe cells don’t express antibodies and divide uncontrollably
Spread to nearby lympho nodes

249
Q

What is the most common presentation of Hodgkin’s lymphoma?

A

persistent cervical and/or supraclavicular lymphadenopathy in a young adult

250
Q

What are the risk factors for hodgkin’s lymphoma?

A

age 20-34 years and >55 years
history of Epstein-Barr virus (EBV) infection
family history of Hodgkin’s lymphoma
young adult in higher socio-economic class (weak)

251
Q

What test is needed to diagnose hodgkin’s lymphoma and what would it show?

A

excisional lymph node biopsy
Reed-sternberg cells

252
Q

What investigations are done for Hodgkin’s lymphoma?

A

Lymph node biopsy (diagnostic)
FBC: low Hb and platelets
comprehensive metabolic panel
erythrocyte sedimentation rate (ESR)
CXR
PET/CT

253
Q

What are the 3 B symptoms that occur in lymphoma?

A

Fever
Night sweats
Weight loss

occur in 30% of patients with HL, usually with advanced disease or other risk factors

254
Q

What staging is used for hodgkin’s lymphoma?

A

Ann-Arbor
(More recently replaced by Lugano)

255
Q

What is stage 1 HL?

A

Involvement of a single lymph node region or lymphoid structure

256
Q

What is stage 2 HL?

A

involvement of 2 or more lymph node regions on the same side of the diaphragm; localized contiguous involvement of only one extranodal organ/site on same side of the diaphragm

257
Q

What is stage 3 HL?

A

involvement of lymph node regions on both sides of the diaphragm, may be accompanied by the involvement of the spleen or one extranodal organ site

258
Q

What is stage 4 HL?

A

diffuse or disseminated involvement of one or more extranodal organs or tissues, with or without associated lymph node involvement

259
Q

What is the treatment for HL?

A

Chemotherapy and radiotherapy

260
Q

What are the differentials for HL?

A

Non-Hodgkin’s lymphoma (NHL)
Lymphadenopathy from other malignancies
Infectious mononucleosis
Reactive lymph nodes

261
Q

What is early favourable/unfavourable HL?

A

Early favourable: stage I to stage II without risk factors
Early unfavourable: stage I to stage II with risk factors

262
Q

What is advanced HL?

A

stage III to stage IV, with or without risk factors

263
Q

Why are low grade lymphoma considered incurable?

A

They often can’t be treated by chemo as it acts on the cell cycle, and these cells are slow growing/ not in cell cycle

264
Q

Examples of some NHLs

A

Diffuse large B-cell lymphoma (DLBCL)
Follicular lymphoma
Mantle cell lymphoma

265
Q

How does diffuse large B cell lymphoma present?

A

a rapidly growing painless mass in older patients

266
Q

What are non-hodgkin lymphomas?

A

NHLs are a heterogeneous group of malignancies of the lymphoid system

267
Q

Who does NHL tend to affect?

A

Uncommon before age of 50, median age at diagnosis 68
Higher chance if first-degree relative has NHL

268
Q

Which viruses are associated with NHLs?

A

HIV and E-BV with Burkitt’s lymphoma
Hep C with DLBCL

269
Q

Risk factors for NHL

A

age >50 years
male sex
some previous viral infections: HIV, Epstein-Barr, H.Pylori, Hep C, HTLV-1
autoimmune conditions: e.g. Sjogren, coeliac

270
Q

What test is helpful for diagnosing T cell lymphomas?

A

Skin biopsy

271
Q

What investigations are run for NHL?

A

Lymph node biopsy
FBC with differential
PET/CT
lactate dehydrogenase (LDH)
Skin biopsy – t cell
Blood smear

272
Q

Differentials for NHL

A

ALL
Infection
Hodgkin lymphoma
Sarcoidosis

273
Q

What are the management options for NHLs?

A

Watchful waiting
Chemotherapy
Monoclonal antibodies (e.g., rituximab, which targets B cells)
Radiotherapy
Stem cell transplantation

274
Q

What are the worst prognostic factors for NHL?

A
  • B symptoms (fever, weight loss, night sweats)
  • Lymphadenopathy
  • Organomegaly
  • Extranodal involvement
  • Poor Eastern Cooperative Oncology Group (ECOG) performance status.
275
Q

What is the official name for glandular fever?

A

Infectious mononucleosis

276
Q

What virus causes glandular fever?

A

Epstein Barr virus in 80-90% of cases

rare but can also be caused by human herpes 6 or CMV

277
Q

Which age group is most commonly affected by glandular fever?

278
Q

Where in the body is Epstein Barr virus found?

279
Q

How can EBV infection be spread?

A

kissing
sharing cups
sharing toothbrushes
other equipment that transmits saliva

280
Q

Symptoms of glandular fever

A

fever
sore throat
enlarged tonsils
malaise
rash
fatigue
splenomegaly
lymphadenopathy

281
Q

What antibodies would be detected for EBV infection?

A

VCA-IgM
VCA-IgG
EA
EBV EBNA

282
Q

What investigations should be run for glandular fever?

A

FBC: lymphocytosis
heterophile antibodies
Epstein-Barr virus (EBV)-specific antibodies
LFTs

283
Q

What is the management for glandular fever?

A

No specific treatment
Just supportive therapy: good hydration, pain relief, rest

284
Q

Differentials for glandular fever

A

Group A strep pharyngitis
Hepatitis A
Acute HIV infection
Adenovirus
Human herpes virus-6
Cytomegalovirus (CMV) infection
Flu

285
Q

3 examples of myeloproliferative disorders

A

Primary myelofibrosis
Polycythaemia vera
Essential thrombocythaemia

also CML, but these 3 can transition to each other

286
Q

What is polycythaemia?

A

an increase in haemoglobin or haematocrit

erythrocytosis

287
Q

What is polycythaemia vera?

A

a chronic myeloproliferative neoplasm.
Characterised by haematopoietic stem cell-derived clonal myeloproliferation that results in erythrocytosis + thrombocytosis, leukocytosis, and splenomegaly

288
Q

What happens in myelofibrosis?

A

proliferation of a single cell line leads to bone marrow fibrosis, where bone marrow is replaced by scar tissue

289
Q

What would a blood film for myelofibrosis show?

A

Teardrop-shaped red blood cells
Anisocytosis (varying sizes of red blood cells)
Blasts (immature red and white cells

290
Q

Who does polycythaemia vera affect?

A

Affects middle-aged or older
Median age at diagnosis is 65 years

291
Q

What mutation almost always causes polycythaemia vera?

A

JAK2 V617F mutation

292
Q

What can PCV progress to?

A

spent phase with anaemia, thrombocytopenia and leukopenia
(myelofibrosis)

293
Q

What is the pathophysiology of PCV?

A

Mutation of JAK2 gene
always active and cells can divide in absence of erythropoietin
leads to rapid proliferation and subsequent death
scar tissue forms
can progress to spent phase and myelofibrosis

294
Q

What are the risk facators for PCV?

A

age >60 years
Budd-Chiari syndrome (BCS)
affected family member
Janus kinase 2 (JAK2) mutations (JAK2 V617F, JAK2 exon 12)

295
Q

Symptoms of PCV

A

headache
generalised weakness/fatigue
pruritus (itching)
night sweats and bone pain
erythromelalgia
splenomegaly
plethora/ruddy cyanosis
blurred vision

296
Q

What would the haematocrit and Hb show in PCV?

A

> 49% in men, >48% in women haematocrit
elevated Hb

297
Q

What investigations should be done for PCV?

A

Haematocrit: >49% in men, >48% in women
Haemoglobin: elevated
Serum ferritin: low or normal
FBC: wbc and platelets elevated
LFTs
JAK2 gene mutation screen

298
Q

What are the differentials of PCV?

A

Secondary polycythaemia
Essential thrombocythaemia (ET)
Primary myelofibrosis
CML
Polycythaemia owing to elevated erythropoietin level
Polycythaemia owing to anabolic steroid or testosterone use
Congenital polycythaemia

299
Q

What is a common complication of polycythaemia and thrombocythaemia?

A

thrombosis leading to MI, stroke or VTE

300
Q

What is the management of PCV?

A

Low risk of thrombosis: Phlebotomy and low-dose aspirin
High risk of thrombosis: cytoreductive therapy (hydroxycarbamide) along with low-dose aspirin (and phlebotomy if required)

301
Q

What is used in the management of myelofibrosis?

A

Ruxolitinib (JAK2 inhibitor)

302
Q

What are some complications of PCV?

A

Thrombosis
Post-PV myelofibrosis
Transformation to acute leukaemia
Haemorrhage

303
Q

What is the most common inherited bleeding disorder?

A

Von Willebrand disease

304
Q

What is type 1 VWD?

A

partial quantitative deficiency of VWF
most common
autosomal dominant

305
Q

What is type 2 VWD?

A

qualitative abnormality of VWF
usually inherited as autosomal dominant

306
Q

What is type 3 VWD?

A

almost complete deficiency of VWF
rarest but most severe form
autosomal recessive

307
Q

What is von Willebrand disease?

A

Caused by a deficiency or abnormality of VWF
The most common inherited bleeding disorder

308
Q

Why does VWD lead to a deficiency of factor VIII?

A

VWF protects factor VIII from premature degradation
so an absence in VWF leads to a deficiency of factor VIII

309
Q

What is the dual haemostatic defect in VWD?

A

Decrease in VWF and Factor VIII

310
Q

What is the pathology of VWD?

A

Mutation on VWF gene on chromosome 12 causes a decrease in working VWF
There isn’t enough working VWF for platelet adhesion and binding to factor VIII

311
Q

Where is VWF synthesised and stored?

A

Endothelial cells and megakaryocytes

312
Q

What stimulates the release of VWF?

A

Histamine and thrombin

313
Q

What causes VWD?

A

Mutation in VWF gene on chromosome 12
very rarely can be acquired

314
Q

If VWD affects men and women equally, why are women more often diagnosed?

A

prominent symptom of menorrhagia

315
Q

Symptoms of VWD

A

Bleeding from minor wounds
Easy and excessive bruising
Menorrhagia
Epistaxis
GI bleeding

316
Q

How would VWD typically present?

A

a history of unusually easy, prolonged or heavy bleeding

317
Q

What investigations would be run for VWD?

A
  • Platelets count: usually normal except in type IIB
  • PT: tests the extrinsic and common pathway and so is normal
  • APTT: tests the intrinsic and common pathways, usually prolonged
  • Measurement of vWF antigen
  • FBC: usually normal
318
Q

What are the differentials for VWD?

A

Mild haemophilia A
Inherited platelet function disorder

319
Q

What are the management options for VWD?

A

Desmopressin (stimulates the release of vWF from endothelial cells)
TXA
Von Willebrand factor infusion (not type 1, more severe)
Factor VIII plus von Willebrand factor infusion (not type 1, more severe)

not required daily, more prohylactic or during bleeding

320
Q

What causes haemophilia A?

A

lack of factor VIII

321
Q

What causes haemophilia B?

A

lack of factor IX

322
Q

What type of inheritance pattern is haemophilia?

A

X-linked recessive

323
Q

What is the pathophysiology of haemophilia?

A

Factors VIII and IX are part of intrinsic clotting pathway.
In haemophilia, there is delayed clot formation due to reduced thrombin generation.
Leads to the formation of an unstable clot that is easily dislodged, causing excessive bleeding

324
Q

What are the risk factors for haemophilia?

A

Family history of haemophilia (congenital haemophilia)
male sex (congenital haemophilia)
age >60 years (acquired haemophilia)
autoimmune disorders (acquired)

325
Q

What are the key presentations of haemophilia?

A

history of recurrent or severe bleeding
bleeding into muscles

326
Q

What are the symptoms of haemophilia?

A

bleeding into muscles (hallmark)
prolonged bleeding following heel prick in neonates
mucocutaneous bleeding
excessive bruising/haematoma
fatigue
menorrhagia and bleeding following surgical procedures or childbirth (female carriers)
extensive cutaneous purpura (acquired haemophilia)

327
Q

Differentials for haemophilia

A

Von Willebrand disease (VWD)
Platelet dysfunction
Deficiency of other coagulation factors
Ehlers-Danlos syndrome
Child abuse

328
Q

What investigations should be done for haemophilia?

A

APTT: prolonged
PT: normal
FBC: normal, possible low Hb
plasma factor VIII and IX assay

329
Q

Management for haemophilia

A

infusion of factor VIII or IX concentrate
can also include: TXA, desmopressin, pain meds

330
Q

Complications of haemophilia

A

Compartment syndrome
Severe bleeding
Joint or muscular damage

331
Q

What are 2 important hallmarks of DIC?

A

continuous generation of intravascular fibrin consumption/depletion of procoagulants and platelets

332
Q

What is disseminated intravascular coagulation?

A

an acquired syndrome characterised by activation of coagulation pathways, resulting in formation of intravascular thrombi and depletion of platelets and coagulation factors

underlying disease statae must be present

333
Q

What is the pathophysiology of DIC?

A

In severe disease states, such as sepsis, malignancy and trauma, more procoagulants are released forming more clots.
This can cause ischaemia, necrosis and organ damage.
But it also depletes supplies of clotting factors and release fibrin degradation products into circulation, interfering more with clot formation

Paradoxical, thrombosis and bleeding

334
Q

What can cause DIC?

A
  • Sepsis
  • Major trauma/ burns
  • Severe organ failure
335
Q

Symptoms of DIC

336
Q

What are the risk factors for DIC?

A

major trauma/burn/organ destruction
sepsis/severe infection
severe obstetric disorders
solid tumours and haematological malignancies
severe toxic or immunological reactions

337
Q

What are the main points of DIC?

A

Requires underlying disease state
Thrombosis and bleeding

338
Q

Investigations for DIC

A

Platelet count: shows thrombocytopenia
Prothrombin time: often prolonged
Fibrinogen: low levels
D-dimer/fibrin degradation products: elevated

339
Q

What is thrombocytopenia?

A

a low circulating platelet count

340
Q

What can cause reduced platelet production?

A

Certain viral infections (e.g., Epstein-Barr virus, cytomegalovirus and HIV)
B12 deficiency
Folic acid deficiency
Liver failure
Leukaemia
MDS
Chemotherapy

341
Q

What can cause increase platelet destruction?

A

Medications (e.g., sodium valproate and methotrexate)
Alcohol
Immune thrombocytopenic purpura (ITP)
Thrombotic thrombocytopenic purpura (TTP)
Heparin-induced thrombocytopenia (HIT)

342
Q

What is immune thrombocytopenic purpura?

A

antibodies are created against platelets.
An immune response against platelets leads to their destruction and a low platelet count (thrombocytopenia)

343
Q

What is thrombotic thrombycytopenic purpura?

A

tiny thrombi develop throughout the small vessels, using up platelets
microangiopathy

344
Q

What can TTP cause?

A

Thrombocytopenia
Purpura
Tissue ischaemia and end-organ damage

345
Q

What is heparin induced thrombocytopenia?

A

involves the development of antibodies against platelets in response to heparin
Heparin-induced antibodies target a protein on platelets called platelet factor 4

346
Q

What are the symptoms of thrombocytopenia?

A

Nosebleeds
Bleeding gums
Heavy periods
Easy bruising
Haematuria (blood in the urine)
Rectal bleeding

347
Q

Top differentials of abnormal or prolonged bleeding

A

Thrombocytopenia
Von Willebrand disease
Haemophilia A and haemophilia B
Disseminated intravascular coagulation

348
Q

What are the risk factors for developing ITP?

A

women of childbearing age
males and females <10 or >65 years old

349
Q

Signs of ITP

A

Purpura
Bleeding

350
Q

What investigations should be done for ITP?

A

FBC
Peripheral blood smear

351
Q

What is the management of ITP?

A

Asymptomatic can just be monitored
A corticosteroid (pred), IVIG, and anti-D immunoglobulin are considered first-line treatments in adults with platelets below 30 × 10⁹/L

352
Q

What is thrombocytosis?

A

High platelet count

353
Q

What causes TTP?

A

Unusually large VWF due to a reduction in ADAMTS-13

354
Q

What are the risk factors for TTP?

A

black ethnicity
female gender
obesity
pregnancy (near term or post-partum period)
cancer therapies

355
Q

Symptoms of TTP

A

Neurological symptoms
Digestive issues
Fever
Bleeding, purpura

356
Q

What investigations would you do for TTP?

A

FBC and platelet count
Shows reduced platelets

357
Q

Management options for TTP

A

plasma exchange
steroids
rituximab

358
Q

What is the prothrombin time test?

A

adding tissue factor and calcium to plasma and establishing length of time to clot
measures factors 7, 10, 5 prothrombin and fibrinogen (the extrinsic pathway)

can also be expressed as INR (international normalized ratio)

359
Q

What does the activated partial thromboplastin time (APTT) measure?

A

Measures factors 12, 11, 9, 8, 10 and 5, prothrombin and fibrinogen (intrinsic pathway)

360
Q

what is lymphopenia?

A

a reduction in the number of lymphocytes in circulating blood

361
Q

What is lymphocytosis?

A

Increase in the number of lymphocytes

362
Q

What is neutropenia?

A

abnormally low level of neutrophils in the blood

363
Q

What is neutrophilia?

A

transient increase in the number of leukocytes in the blood

Phase 2a (14 decks)

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