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Haematology Flashcards

1
Q

What’s the colour of the blood sample bottle used for FBC

A

Purple

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2
Q

What is the yellow blood sample bottle used for

A

Urea and electrolytes

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3
Q

What tests are in an FBC for RBCs (selected)

A
  • Haemoglobin
  • Haematocrit
  • Mean Corpuscular Volume
  • Red cell count & distribution width
  • Reticulocyte count
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4
Q

Haemoglobin in FBC
- affected by

A

high = polycythaemia; low = anaemia
→ grams per litre
- Iron deficiency
- active bleeding
check for pancytopenia (marrow issue)

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5
Q

Haematocrit in FBC
- what is it

A

→ L / L
- % of sample made up of RBC
- affected by number of RBC and volume of blood plasma
→ watch for hyperviscosity syndrome (too thick) during polycythemia

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6
Q

Mean Cell/Corpuscular Volume in FBC

  • what is it
  • what is it useful for
A

→ phenol litres

  • average size of RBC in sample
  • useful in anaemia: indicates cause
  • classified macrocytic / normalcytic / microcytic
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7
Q

Red cell count & distribution width
- what are they & what are they useful for

A

RCC
= # of RBC present per unit volume of blood
- use with Hb & Hct to confirm anaemia / polycyth

RDW
= in depth look at MCV, provided in range (big-small) so useful when mixed cell size (anisocytosis - associated with iron deficiency) and anemia

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8
Q

Reticulocyte count

  • what is it
  • a brief interpretation of results
A

= shows # of fresh, newly produced RBC (in the bone marrow)

so if anaemia:
→ a raised rc count = marrow is producing, but rbc is getting destroyed
→ a low rc count = marrow not producing enough
no anaemia:
→ a raised rc count = compensating for blood loss or adapting to oxygen demand

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9
Q

A raised WBC is known as

A

Leukocytosis
- to treat: determine rate and which type (typically neutrophils and lymphocytes)

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10
Q

A lower WBC is known as

A

Leukopenia
- to treat: determine rate and which type (typically neutrophils and lymphocytes)

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11
Q

What is in a ‘differential’?

A

Tests separately for different types of WBC but most importantly **counts blasts in circulation**

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12
Q

Neutrophils:

  • function
  • lifespan
  • structure & % of leukocyte
A
  • early phagocytosis of pathogen, involved in acute infect (partt bacteria) & inflamm
  • 10 hours
  • multi-lobed nucleus, 40-60%
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13
Q

Lymphocytes

  • subtypes & function
  • lifespan
  • structure & % leukocytes
A
  • B lymphocytes - plasma / memory cells & produce antibodies
  • T lymphocytes: T helper / cytoxic / natural killer: kills virus infected cells
  • 8-12 hours
  • fried egg appearance
  • perinuclear hoff around golgi, 20-40%
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14
Q

Monocytes

  • function
  • structure & % of leukocyte
A
  • differentiates into macrophages → tissue resident
  • major phagocytotic role
  • can become antigen presenting cells
  • reniform nucleus
  • 2-10%
  • Kupffer, osteoclast & alveolar macrophages
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15
Q

Eosinophils

  • function
  • lifespan
  • structure & % of leukocyte
A
  • Neutralises histamine
    = antagonist to basophils & mast cells
  • bi-lobed, pink lozenge, distinctive granules
  • 1%
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16
Q

Basophils

  • function
  • lifespan
  • structure & % of leukocyte
A
  • Involved in allergic reaction & inflammation
  • produces histamine
    = release vasoactive substances
    = antagonist to eosinophils
  • bi-lobed, dark blue granules of histamine
  • 0.5%
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17
Q

Blasts

  • what are they
  • where are they usually found?
A

= immature cells
- typically found in bone marrow where they mature (are then released)

→ so blasts in circulation = abnormal!
can be caused by
- leukaemia
- myeloproliferative disorders
- chemo or treatment with G-CSF

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18
Q

Define thrombocytosis

A

raised platelet count

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19
Q

What’s in an iron study?

A
  • ferritin
  • serum iron
  • transferrin saturation / total iron binding capacity
  • most useful for patients with anaemia and a chronic disorder
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20
Q

Ferritin

  • what does it measure
  • when would it be abnormal?
A
  • measure of iron stores
  • may be increased in: inflammation, tissue destruction, liver disease, malignancy, iron replacement
  • used to diagnose iron deficiency and anaemia
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21
Q

Serum iron

  • what does it measure
  • what can it be affected by
A
  • amount of iron in the blood
  • can be affected by circadian rhythm so usefulness?
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22
Q

Transferrin

  • what is it?
  • what is it like in iron deficiency?
A
  • protein used to transport iron around the body
  • in iron deficiency: synthesis is increased but saturation is low (less of it is occupied)
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23
Q

TIBC
- what is it

A

Total iron binding capacity
- measures all of the proteins in the serum that binds iron, transferrin being the principle

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24
Q

Define anaemia

A

where there is decrease of haemoglobin in the blood below the reference level for the age and sex of individual

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25
Q

Two pathological cause of anaemia

A
  • decreased production: deficiencies iron / folate / B12 OR bone marrow failure
  • increased loss: is the patient bleeding OR are RBC being destroyed (haemolysis) - vascular system or spleen?
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26
Q

How are anaemia classified

A

Based on mean corpuscular volume - how big the cells are: macrocytic / normocytic / microcytic

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27
Q

What is macrocytic anaemia and what causes it?

A
  • RBC is bigger than normal
  • Depending on the size of the erythroblasts (megaloblastic or non), it can be caused by folate / B12 deficiencies or others
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28
Q

How is macrocytic anaemia classified by cause?

A
  • megaloblastic: vitamin B12 deficiency (pernicious anaemia) / folate deficiency
  • normoblastic: alcohol, liver disease, hypothyroidism, haemolysis, marrow issues, myeloma, azathioprine
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29
Q

Folate physiology:

  • where is it found
  • how is it used in the body
A

found in
green vegetables, e.g spinach and brocco

low body stores of around 4 months, essential for DNA synthesis

deficiency =
delayed nuclear maturation so larger RBC and decreased RBC production in marrow
& neural tube defect in foetus

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30
Q

Presentation of folate deficiency

A
  • anaemia symptoms = pallor, fatigue, dyspnoea, anorexia, heachache
  • glossitis (red sore tongue can occur)
  • no neuropathy unlike B12
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31
Q

What causes folate deficiency?

A
  • poor nutrition
  • malabsorption: coeliac, crohn’s, pregnancy, haemolysis
    = main cause of macrocytic anaemia
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32
Q

How would you treat folate deficiency

A

→ check for vitamin B12, if deficient replace B12 first
- replace orally

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33
Q

What causes B12 deficiency?

A

MALABSORB

  • surgery: gastrectomy / ileal resection
  • pernicious anaemia (= autoimmune malabsorp)
  • diseases: crohn’s, coeliac

INSUFFICIENT DIET INTAKE

OTHERS

  • metformin, PPI, H2 receptors
  • nitric oxide recreational use

= marocytic, megaloblastic anaemia

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34
Q

Presentation of vitamin B12 deficiency anaemia

A

anaemia symptoms
fatigue, headache, pallor, dyspnoea, anorexia, tachy & palp

glossitis, angular stomatitis / cheilosis
ulcers in corner of mouth

lemon yellow skin due to pallor + jaundice
from excess breakdown of Hb

! neurological symptoms !
differentiate from folate deficiency
- Peripheral neuropathy with numbness or paraesthesia (pins and needles)
Loss of vibration sense or proprioception
Visual changes
Mood or cognitive changes

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35
Q

What is pernicious anaemia?

A

autoimmune condition where gastric parietal cells (produces intrinsic factor needed to absorb vitamin B12) are destroyed or lost

→ need IM replacement and not oral

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36
Q

How would you

  • diagnose general B12 deficiency
  • differentiate pernicious anaemia from general B12 deficient anaemia
A
  • FBC, blood smear, reticulocyte count, serum vitamin B12
    → macrocytic, megaloblastic anaemia
  • test for intrinsic factor antibodies
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37
Q

How would you treat vitamin B12 deficiency

A
  • replace intramuscularly (esp for pernicious anaemia), then needed for maintenance
  • IM hydroxocobalamin
  • for dietary deficient people → oral replacement
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38
Q

Cause of normocytic anaemia

A
  • acute blood loss
  • anaemia of chronic disease
  • aplastic & haemolytic
  • endocrine disorders (hypothyroidism )
  • renal failure
  • pregnancy
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39
Q

Clinical presentation of normocytic anaemia

A
  • fatigue, headaches and faintness
  • dyspnoea and breathlessness
  • angina if preexisting coronary disease, palpitations
  • anorexia
  • palpitations
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40
Q

How would you diagnose normocytic anaemia

A

principle of exclusions:

  • normal B12 and folate
  • raised reticulocytes
  • Hb down
  • blood count and film: RBC are normocytic
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41
Q

How would you treat normocytic anaemia

A
  • treat underlying cause
  • improve diet with plenty of vitamins
  • erythropoietin injections
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42
Q

Cause of microcytic anaemia

A

= TAILS

  • thalassaemia
  • anaemia of chronic disease
  • iron deficiency anaemia
  • rarely: lead poisoning/ congenital sideroblastic anaemia
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43
Q

What is sideroblastic anaemia?

A

when red cells fail to completely form haem
iron deposits which form a ring around nucleus = sideroblast

→ ‘basophilic stippling of RBC’

supportive tx,
if acquired = alcohol

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44
Q

Common causes of iron deficiency

A
  • impaired absorption: coeliac, gastrectomy, diet: v’s, the elderly
  • assume blood loss until proven otherwise!
  • gastrointestinal malignancy for everyone
  • women = menstruation, pregnancy (transfer to foetus)
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45
Q

Presentation iron deficiency

A

anaemia = fatigue, dyspnoea on exertion
glossitis, angular stomatitis / cheilosis

restless legs syndrome

pica = ED, eating non-food

nail changes: thinning, flattening then spooning (last is rare)

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46
Q

Iron physiology

  • function
  • absorption to function
A

required for the formation of the haem of haemoglobin
transported into duodenum by HCP1,

intracellular storage form = ferritin (intracellular store for iron)

circulate around the body = bound to transferrin

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47
Q

Results needed to diagnose iron deficiency

A

RBC = microcytic, hypochromic (pale)
poikilocytes (vary in shape), anistocytes (vary in size)

serum ferritin = low (simple i.a.) /
normal in malignancy

  • *→ low transferrin saturation** (<16%)
  • *high** total iron binding capacity
  • *low** reticulocyte count
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48
Q

How would you manage iron deficiencies

A
  • investigate / treat source of blood loss
  • replace iron → **oral is preferred (safer), IV is no faster than oral**!
  • Hb should rise approx 20g every 3-4 weeks
  • **ferrous sulphate** 200mg 1-3x daily
  • after normal: continue supplementation for further 3 months to replenish stores
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49
Q

Side effects of ferrous sulphate // alternative therapy

A
  • nausea, abdominal discomfort, diarrhoea / constipation and black stools
  • IV or deep IM iron not absorbing or intolerant
  • ferrous gluconate if bad SE
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50
Q

What is haemolytic anaemia and how is it classified?

A

premature breakdown of RBCs before their normal lifespan of around 120 days

  • compensated - increased destruction matched by increased synthesis
  • decompensated - rate of destruction exceeds rate of synthesis
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51
Q

Cause of haemolytic anaemia

A

Hereditary
spherocytosis / elliptocytosis /
Hb disease = sickle cell, A/B thalassaemia
G6PD deficiency

Acquired
autoimmune / prosthetic valve related

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52
Q

Tests used to investigate haemolytic anaemia

A

FBC: normocytic anaemia

blood films
reticulocyte ++, bilirubin (unconj +++),
RBC fragments = schistocytes / spherocytes / sickle cell, haptoglobin

direct Coomb test: to see if autoimmune

Liver function test
(but liver might be able to compensate and conj)

Lactose dehydrogenase ++

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53
Q

Presentation and results for diagnosing haemolytic anaemia

A

Anaemia = fatigue, glossitis, pallor (pale)

Splenomegaly = congested Hb
Jaundice = haemolysis
Abdo pain = gallstones
Dark urine = Hb uria

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54
Q

Physiology of bilirubin and how would you use it to diagnose haemolytic anaemia

A
  • yellow bile pigment from breakdown of Hb (haemolysis)
  • unconjugated (indirect) - insoluble, travel in bstream bound to albumin
  • conjugated (direct) - processed in the liver so soluble & excretable
  • urobilinogen = end product of conjugated haemoglobin

usually in haemolytic anaemia, unconjugated is increased = as increased Hb breakdown, faster than liver can process

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55
Q

Physiology of haptoglobin and how would you use it to diagnose haemolytic anaemia

A

protein made in the liver trying to mop up free haemoglobin (loose in blood stream can cause problems) therefore if values are low = busy = issue!

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56
Q

G6PD

  • what is it
  • pathophysio for **deficiency**
A

Glucose-6-Phosphate-Dehydrogenase deficiency

  • vital enzyme to ensure normal lifespan of RBC, protect from oxidative damage
  • (inherited) deficiency will mean sudden destruction of RBC and can lead to haemolytic anaemia
  • malaria protective trait as parasites cannot survive on these RBC
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57
Q

Presentation of G6PD deficiency

A

most are asymptomatic but may have oxidative crisis due to reduced glutathione (partner of G6PD in protecting RBC) production.

Mostly precipitated by acute drug-induced haemolysis from
aspirin, antimalaria (-quine drugs), antibac’s, fava beans

Attacks are due to rapid intravascular haemolysis → anaemia, jaundice and haemoglobinuria

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58
Q

Investigate and diagnose for G6PD deficiency

A
  • blood count normal between attacks
  • blood film during attack has irregularly contracted cells, bite cells and increased reticulocytes
  • G6PD enzyme will be low, but immediately after attack might have false high concentration
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59
Q

Treatment G6PD deficiency

A
  • stop drugs / fava beans
  • blood transfusion
  • splenectomy isn’t usually helpful
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60
Q

What is Hereditary spherocytosis

A

inherited - autosomal dominant but 25% spontaneous

defects in Hb membrane → cells become spherocytic
= more rigid, less deformable

trapped in spleen → destroyed via extravascular haemolysis

(risk = family history)

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61
Q

Present hereditary spherocytosis

A
  • jaundice - at birth but may be delayed
  • may eventually develop anaemia
  • ulcers on the leg, splenomegaly, gall stones (from chronic haemolysis)
  • course of illness may be interrupted by either aplastic anaemia (sudden stop in BC production) or m_egaloblastic anaemia_ (folate) caused by hyperactivity of the bone marrow
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62
Q

How would you diagnose hereditary spherocytosis

A
  • blood film showing spherical RBCs and reticulocytes
  • blood count with low Hb and increased retic
  • haemolysis: serum bilirubin and urinary urobilinogen is raised
  • direct antiglobulin (Coomb’s test): negative, thus ruling out autoimmune haemolytic anaemia
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63
Q

What is Hereditary Elliptocytosis?

A

RBC are ellipse shaped

autosomal dominant

presents & manages same as hereditary spherocytosis

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64
Q

How would you treat hereditary spherocytosis & elliptocytosis

A
  • splenectomy will relieve symptoms due to anaemia or splenomegaly, reverse growth failure and prevent recurrent gallstones (if issue = cholecystectomy)
  • best to postpone until after childhood due to infections post-op
  • after operation: do appropriate immunisation and lifelong penicillin prophylaxis, folate supplements
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65
Q

Source of RBC?

A

Bone marrow
Made from erythroblasts

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66
Q

What is erythropoietin?

A
  • Hormone made in the kidneys
  • Used by bone marrow to stimulate production of RBC
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67
Q

Structure of haemoglobin

  • general structure formula
  • Adult, foetal and delta
  • % composition of an adult
A

haemoglobin + enzymes + membrane

  • HbA = haem + 2 alpha + 2 beta chains
  • HbFoetal = haem + 2 alpha + 2 gamma chains
  • HbA2 = haem + 2 alpha + 2 delta chains
  • HbA 97%, HbA2 2%, HbF = 1%
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68
Q

Foetal haemoglobin

  • where is it made
  • when does the shift to adult haemoglobin occur
A
  • made in liver and spleen, relied on in utero
  • upgrade to adult haem production before delivery
  • survives fully on adult haemoglobin up to 6 months
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69
Q

Haemoglobinopathies: disease principle (how do things go wrong?)

A
  • thalassaemias are disorders of quantity (reduced production)
  • sickle cell anaemia is a disorder of quality
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70
Q

Sickle cell anaemia

  • cause
  • subdivision
A
  • single point mutation in beta globin gene.
  • inherit from both **autosomal recessive** or carrier
  • so - sickle cell anaemia (homozygous) or compound heterozygous with different abnormality from each parent but may still present like sickle cell disease
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71
Q

Patho for sickle cell anaemia

A
  • instead of HbA, HbS are made
  • in deoxygenation: HbS - polymerises → changes to sickle shape
  • blocks blood vessels
  • chronic haemolysis (low baseline Hb)
  • acute complications & chronic organ damage
  • normal Hb for child with sickle cell is 60-100
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72
Q

Nature of onset of sickle cell anaemia?

A
  • Will not present until patient is at least 6m (switch to HbA)!
  • any acute presentation = medical emergency
  • urgent analgesia for painful crisis
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73
Q

Present - short term for sickle cell anaemia

A
  • vaso-occlusive crises - acute pain in hand and feet due to vasoocclusion (children), pain in long bones (femur, spine, ribs and pelvis) due to avascular necrosis (adult)
  • Splenic sequestration (trap in spleen) = megaly + fall in Hb
  • acute chest syndrome - shortness of breath, chest pain, hypoxia
  • pulmonary hypertension - mean pulmonary artery pressure > 25 mmHg by right heart catheterisation, → stroke, dactylitis, priapism
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74
Q

Present - long term for sickle cell anaemia (5)

A
  • delay in growth:
    weight, sex maturation
    avascular necrosis of bones, dactylitis, osteomyelitis due to infections,
  • neurological TIA, fits and cerebral infarction 25%
  • splenic infarctions over time → autosplenectomy (acute = splenic sequestration)
  • liver - chronic hepatomegaly and liver dysfunction bc trapping of sickle cells
  • cardio - normally hypertrophy → works hard to pump blood → more at risk for systolic and diastolic disorders
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75
Q

Aetiology for sickle cell anaemia

A
  • protects against malaria
  • african, afro carribean, southern asian
  • family history
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76
Q

How would you diagnose sickle cell anaemia

A
  • *Antenatal** = molecular genetics test → preg mums
  • *Heel prick test** = 5 days after birth

for types of Hb
High performance liquid chromatography
Gel / Hb electrophoresis

for the trait
Sickle solubility test

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77
Q

treatment options for sickle cell anaemia

A
  • treat infections if needed
  • transfuse
  • exchange
  • top up
  • pharma
  • **hydroxycarbamide**
  • switches back on patient’s foetal haemoglobin production
  • reduce sickle cell complications as foetal usually no problems
  • folic acid to all haemolysis patients!
  • bone marrow transplant only curative option available
  • gene therapy
  • lentiviral (uses virus to bring in new gene)
  • crispr / cas9 genome edit
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78
Q

Subtypes and pathology of thalassaemia?

A
  • alpha & beta thalassaemia
  • for each type there is under or no synthesis for that chain (normal = balanced 1:1 production)
  • consequence = ineffective erythropoiesis and haemolysis
  • autosomal recessive - if carriers might still have mild anaemia
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79
Q

Beta thalassaemia: cause, if heterozygous?

A
  • little to no B chains - so lots of alpha therefore more HbA2 and HbF
  • due to point mutations
  • if heterozygous then asymptomatic microcytosis with or without mild anaemia
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80
Q

Presentation - Beta thalassaemia major (homozygous)

A
  • recurrent bacterial infections
  • severe anaemia from 3m - 6m (switch from gamma to beta)
  • **extramedullary haematopoiesis** (ineffectve RBC production outside marrow) resulting in hepatosplenomegaly and bone expansion
  • **thalassaemia face**: small face, smooth philtrum, short nose, thin upper lip, underdeveloped jaw
  • hypertrophy of ineffective bone marrow = bone abnormalities
  • hair on end sign
  • Bloods: microcytic, irregular, hyperchromic RBC, normal ferritin
    = lifelong transfusion dependent!
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81
Q

Presentation - Beta thalassaemia minor (heterozygous)

A

= common carrier state

  • asymptomatic
  • anaemia is mild or absent
  • RBC is hypochromic (pale), and microcytic with a low MCV
  • **distinguish from iron deficiency**: serum ferritin and iron stores normal
  • raised HbA2 and often HbF
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82
Q

Presentation classified as beta thalassaemia intermedia

A

= includes those who are symptomatic with moderate anaemia that do not require regular transfusions

  • splenomegaly
  • bone deformities
  • recurrent leg ulcers
  • gallstones
  • infections
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83
Q

Treatment beta thalassaemia - general plan?

A
  • transfusion - depends on type but goal is to keep Hb above 90g/L to suppress extramed haematopoeisis
  • iron-chelating agents **or DEFRIPRONE or sc DESDERRIOXAMINE** to prevent iron overload / ascorbic acid increase urinary excretion of iron
  • splenectomy but not in childhood (infection)
  • bone marrow transplant
  • long term folic acid
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84
Q

Complications of transfusions

A
  • progressive increase in body iron load
  • in liver and spleen: liver fibrosis and cirrhosis
  • in endocrine glands and heart: diabetes, hypothyroid/calcaemia & premature death
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85
Q

alpha thalassaemia: cause

A
  • gene deletions on chromosome 16
  • can be one or both alpha chain gene deletions
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86
Q

presentation alpha thalassaemia

A
  • *4 gene deletion** (both genes both chromosomes, –/–)
  • only Hb Barts present = 4 gamma chains, cannot carry O2 and incompatible with life
  • stillborn or shortly after birth. pale, oedematous and enormous livers and spleens (hydrops fetalis)
  • *3 gene deletion** (a-/–)
  • HbH disease with 4 beta chains
  • moderate anaemia and splenomegaly
  • usually not transfusion dependent
  • *2 gene deletion** - trait carrier (aa/– or a-/a-)
  • microcytosis with or without mild anaemia
  • *single gene deletion** - silent carrier (aa/a-)
  • usually a normal blood picture
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87
Q

Aplastic anaemia due to bone marrow failure
- what is it

A

Pancytopenia
= reduction in all major cell lines, red / white / platelets; with
aplasia (hypocellularity) of the bone marrow
= marrow stops making cells

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88
Q

Cause of aplastic anaemia

A
  • idiopathic acquired (67%)
  • benzene, toluene and glue sniffing
  • chemo drugs
  • antibiotics, infections
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89
Q

Pathophysio of aplastic anaemia

A
  • due to reduction in number of pleuripotent stem cells, together with fault in those remaining
  • or immune reaction against pleuripotent stem cells - unable to repopulate bone marrow
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90
Q

Present of aplastic anaemia

A
  • symptoms from the deficiency of the three: anaemia, infection, bleeding - gums, bruising with minimal trauma, blood blisters in mouth
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91
Q

How would you diagnose aplastic anaemia?

A
  • blood count - pancocytopenia with low reticulocyte count
  • bone marrow exam: hypocellular marrow with increased fat spaces
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92
Q

How would you treat aplastic anaemia?

A
  • TUC
  • main concern = infection - so any with severe neutropenia & fever give broad spectrum parenteral antibiotics urgently
  • RC transfusion and platelet

Long term

  • if under 40: bone marrow transplant: HLA identical sibling or donor
  • over 40 / with severe disease and no sibling donor / transfusion dependent: immunosuppresive therapy with antithymocyte globulin (ATG) and cyclosporin
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93
Q

What does it mean if a haematological condition is lymphocytic / lymphoblastic

A

cancerous change takes place in mature blood stem cell in the marrow that normally develops into **lymphocyte**

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94
Q

What does it mean if a haematological condition is myeloid

A

mutation occurs in bone marrow cell that would develop into **RBC, WBC or platelet (aka not lymphocyte)**

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95
Q

What does it mean if a haematological condition is acute

A

progresses rapidly and affect cells that are not fully developed

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96
Q

What does it mean if a haematological condition is chronic

A

progress slowly, patients have a greater number of mature cells

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97
Q

Acute Lymphocytic Leukaemia

  • What is it
  • What cells do they affect
  • Common incidence
A

= malignancy of the lymphoblast → gives rise to T cells and B cells!

  • precursor cell, which predominantly lives in the marrow
  • bimodal incidence, lots in <20 then more later on
98
Q

Risk for Acute Lymphocytic Leukaemia

A
  • age - less than 5 (2-4), mid 30’s, mid 80’s
  • radiation esp during pregnancy
  • benzene - solvents
  • smoking
  • down syndrome
  • immunodeficiency
99
Q

Acute Lymphocytic Leukaemia - pathology

A

arrest maturation of lymphocytes and promotes controlled proliferation of immature blast cells in marrow

B cells = in children T cells = in adults

genetics and environmental trigger

100
Q

Acute Lymphocytic Leukaemia - Present

A

anaemia, thrombocytopenia (easier bleeding), leukopenia (+ infections)

enlarged lymph nodes (!!)

enlarged spleen/liver due to infiltration

thymus enlargement
= mediastinum masses with SVC obstruction

neuro palsies / involvement

(if gum enlargement = AML!)

101
Q

Signs of Marrow failure

A
  • low Hb = Anaemia = breathlessness, fatigue, angina and claudication / pallor, murmur
  • low WBC = infection = fever and mouth ulcers
  • low platelets = bleeding & bruising
102
Q

Acute Lymphocytic Leukaemia - Investigations

(& what is it again?)

A

1st line bloods = FBC + UE,
peripheral blood smear → diff M or L

HLA typing

  • *CXR** - look for mediastinal and abdominal lymphadenopathy
  • *lumbar puncture / pleural tap** for CNS involvement
103
Q

Acute Lymphocytic Leukaemia - Treatment options

A

chemotherapy = in course & diff dose
focus on the brain: will relapse and chemo doesn’t get through blood brain barrier = intrathecal therapy - chemo delivered through lumbar puncture

  • *supportive**
  • blood and platelet transfusions
  • antiviral / bac / fungals from neutropenia
  • *GOLD = transplant = stem cell / bone marrow**
  • molecular MRD (minimal residual disease) - decide based on this aka tech to look for remaining disease
104
Q

Acute Lymphocytic Leukaemia - complications - 3i’s

A
  • induction mortality - 4.7% (dying in the first month)
  • interact of chemo with other drugs
  • infection
105
Q

Acute Lymphocytic Leukaemia - new drug options (4) and their mechanisms

A

Monoclonal antibodies: attach to CD20 via link molecule
brentuximab, inotuzumab
liver tox

BiTE - similar to monoclonal antibody
= uses T cell to kill B cell

  • *Autologous CAR-T production**
  • take out T cell, genetically engineer and put back, kills cancer
106
Q

Chronic Lymphocytic Leukaemia
- What is it

A

= accumulation of CLL cells (partially mature B cells that have escaped apoptosis and undergone cell arrest) in the body from acquired genetic mutation → crowd out healthy cells

107
Q

Subtypes of Chronic Lymphocytic Leukaemia
- does it matter?

A

→ Small Lymphocytic Lymphoma = when abnormal B cells in lymphoid tissues

→ Chronic Lymphocytic Leukaemia = when abnormal B cells are deposited in blood and bone marrow, and often in spleen and lymph nodes

→ same type of cells and treatment, just location

108
Q

Risk of Chronic Lymphocytic Leukaemia

A
  • normally later in life
  • pneumonia may be triggering event
  • mutations, trisomies and deletions influence risk
109
Q

Presentation Chronic Lymphocytic Leukaemia

A
  • elevated WBC = most common finding
  • fatigue / shortness of breath during normal physical activity
  • lymph node enlargement**
  • *If severe**
  • low grade fever
  • unexplained weight loss
  • night sweats
  • feeling of fullness due to enlarged spleen or liver
  • infection of skin, lungs or sinuses
110
Q

Differentiate CML from CLL on a blood smear?

A

CLL = smudge cells
immature B cells broken during the smear

CML = increased granulocytes and monocytes

111
Q

Complications of Chronic Lymphocytic Leukaemia

A
  • autoimmune haemolysis
  • increased risk of infection due to hypogammaglobulinaemia (low lgG)
  • marrow failure
112
Q

Treatment for Chronic Lymphocytic Leukaemia

A
  • blood transfusions
  • human IV immunoglobulins
  • chemo or radio
  • stem cell transplant
113
Q

Prognosis of Chronic Lymphocytic Leukaemia

A
  • may stay stable for years, but death is often due to complication of infection
  • may transform into aggressive lymphoma = Richter’s syndrome

Rule of 3rd’s

  • 1/3 will never progress
  • 1/3 progress slowly
  • 1/3 progress actively
114
Q

What is intrathecal therapy?

A

chemo delivered into the brain (so it will cross blood brain barrier) through lumbar puncture

115
Q

What is Acute Myeloid Leukaemia

A

= heterogenous clonal malignancy characterised by

  • immature myeloid cell proliferation (≥ 20% blasts in peripheral blood!)
  • bone marrow failure
116
Q

What do myeloid cells give rise to?

A

Myeloid cells gives rise to basophils, neutrophils and eosinophils

117
Q

Aetiology of Acute Myeloid Leukaemia?

A
  • about 3-4k cases every year, but increasing over time
  • 85-89 yo peak age of AML cases
  • majority are not hereditary
118
Q

Symptoms of Acute Myeloid Leukaemia?

A
  • hepatomegaly and splenomegaly
  • gum hypertrophy ** → unique!!
  • anaemia (fatigue, shortness of breath, lightheadedness) and thrombocytopenia (bleeding / bruising) symptoms
  • Disseminated intravascular coagulation (bruising, blood clots, confusion) occur in subtype of AML where there is release of thromboplastin
119
Q

how would Acute myeloid Leukaemia present on an FBC?

A

white cell counts can be anything!
risk of frequent and / or severe infections → large proportion of whites are normal

other blood counts unusually low
Red: fatigue, shortness of breath, lightheadedness
Platelets: bleeding / bruising

blasts in peripheral blood!
deterioration in FBC parameters is very rapid, in days / weeks!

120
Q

How would you diagnose Acute Myeloid Leukaemia & how would you differentiate it from ALL

A
  • *peripheral blood smear** (→ myeloblast or lymphoblast) & bone marrow biopsy
  • Differentiation from ALL is based on microscopy, immunophenotyping and molecular methods
121
Q

Differential diagnosis for Acute Myeloid Leukaemia

A
  • B12 or folate or mixed haematinic deficiency
  • infection - retroviral disease, herpesvirus
  • medication / autoimmune
  • liver disease (e.g. cirrhosis)
122
Q

How would you treat Acute Myeloid Leukaemia

A
  • allopurinol for tumour lysis syndrome prevention
  • chemo
  • usually a combination, manage dose carefully to optimise balance between destroyed leukaemic cells and not damaging other normal cells
  • usually administered on IV, anthracycline, cytarabine
  • may suggest patient to have a Hickman / PICC line / portacath
123
Q

Alternative to allopurinol and mechanism?

A

febuxostat

xanthine competitive inhibitor
(allopuinol is direct xanthine inhibitor)

124
Q

What is a Hickman / PICC line / portacath

A

= central venous catheters, inserted into the veins at chest or neck area

Useful for

  • giving meds / fluids that can’t be taken by mouth or would hurt a small vein
  • obtaining bloods when often needed
125
Q

General supportive measures for chemotherapy?

A
  • fertility cryopreservation - semen storage for men
  • transfusion (red cells, platelets, treatment of infection)
  • clinical trial availability: offer novel therapeutic options for patients
  • offer diagnostic / test modalities not necessarily offered as standard of care
  • bystander damage to other organs can occur!
126
Q

What is the less intensive treatment regime for AML?

A
  • usually for older / less fit individuals
    outpatient
  • azacytidine
  • low dose subcut cytarabine
  • with supportive measures
127
Q

Typical ‘anaemia’ symptoms

A

fatigue, headache, pallor, dyspnoea, anorexia, tachy and palpitations

128
Q

What is Chronic Myeloid Leukaemia

A

= abnormal (partially mature) and overproduction of granulocytes caused by chromosomal genetic mutation BCR-ABL1 gene

= myeloproliferative neoplasm

129
Q

Risk factors for Chronic Myeloid Leukaemia

A
  • disease of adults, rare in childhood
  • most often 40-60, male
130
Q

Pathology of Chronic Myeloid Leukaemia - how does it start?

A
  • translocation chromosomal error during which a fusion gene is produced → BCR-ABL1 gene
  • translocation between parts of chromosome 9 & 22 in a single bone marrow cell during cell division
    = 9 is longer, 22 is shorter → Philadelphia chromosome
131
Q

Function of the BCR ABL Gene?

A

BCR-ABL creates protein → produces excessive tyrosine kinase = constant cell division

→ myeloid cells divide quickly & partially mature!
= buildup & symptoms of AML

132
Q

How is Chronic Myeloid Leukaemia categorised?

A
  • patients with detectable philly chromosome = Ph+ CML (95%), none = PH- CML
  • may also be atypical CML not caused by BCR-ABL1 gene! must assess as poor prognosis and may not respond to treatment
133
Q

Signs and Symptoms Chronic Myeloid Leukaemia

A
  • ymptomatic anemia: weakness, fatigue, shortness of breath during basic everyday activities
  • fever, bone pain
  • unexplained weight loss
  • **pain or feeling of fullness below the ribs on the left** due to **enlarged spleen**
  • fullness on the LUQ
  • palpable spleen?
  • night sweats
  • gout due to purine breakdown
  • bleeding due to platelet dysfunction
134
Q

Investigations for Chronic Myeloid Leukaemia

A

full FBC & blood film
bone marrow biopsy = hypercellular

Genetics
karyotyping → checks for chromosomal abnormalities or cytogenetics!

PCR for most sensitive test used to detect and measure the quantity of BCR-ABL1 gene (Ph does not matter here)

135
Q

Diagnosing criteria for Chronic Myeloid Leukaemia

A
  • increased WBC (granulocytes)
  • with spectrum of myeloid cells (3 phils and myelocytes)
  • blasts in smears!
  • normally not present in blood of healthy individuals!
136
Q

Treatment plan for Chronic Myeloid Leukaemia

A
  • use PCR results to determine baseline BCR-ABL1 gene amount

biological therapy: tyrosine kinase inhibitor
= Imatinib (dasatinib, nilotinib, etc )

Monitoring
FVC, spleen size, PCR repeat for BCR-ABL-1

gold is probably stem cell transplant

137
Q

Prognosis of Chronic Myeloid Leukaemia depends on:

A
  • phase of CML
  • age
  • spleen size
  • platelet count
  • blasts in the blood & increased number of basophils
138
Q

What are Myeloproliferative Neoplasms (with 3 examples!)

A

= group of blood cancers in which too many blood cells are made in bone marrow
= e.g. primary thrombocytosis = essential thrombocythaemia // polycythaemic vera // myelofibrosis

139
Q

Main cause of myeloproliferative neoplasms

A

JAK2 mutation
JAK2 protein → signals for promotion of growth and division of cells
helps control big3 blood cells

increased production of big 3 + prolonged survival

overproduction of cytokines too = + inflammation

140
Q

Targeted treatment for cause of myeloproliferative neoplasms?

A

Ruxolitinib
= Janus Kinase inhibitor
= cancer growth blocker

for intermediate to high risk
intolerance to hydroxyurea & steroid refractory GvHD

141
Q

Polycythaemia Vera - what is it?

A

RBC count above the normal range

142
Q

Inflammatory symptoms for Myeloproliferative Neoplasms

A
  • unexplained fevers
  • night sweats
  • itchy skin = pruritus - esp after hot shower
  • reddening of face
  • bone pain
143
Q

Neurological symptoms for Myeloproliferative Neoplasms

A
  • headaches, dizziness and weakness
  • difficulties concentrating
  • peripheral neuropathy (numbness, tingling or burning in the feet)
144
Q

Symptoms and signs - Polycythaemia Vera

A
  • inflammatory and neurological symptoms for MN’s
  • Conjunctival plethora (excessive redness to the conjunctiva in the eyes)
  • A “ruddy” complexion
  • erythromelalgia: burning in fingers and toes
  • hepatosplenomegaly: due to extramedullary haemopoiesis → distinguishes PV from secondary causes!
  • uncontrolled bleeding or excessive bruising
  • abnormal blood clots
  • weight loss with no known reason
  • full after eating small amounts of food
145
Q

Complications Polycythaemia Vera

A
  • stroke
  • heart attack
  • thrombus / DVT
  • enlarged spleen
  • progression to myelofibrosis, MDS or AML
146
Q

Pathology of Polycythaemia Vera

A

mutation in the JAK2 gene
JAK2 protein made signals for promotion of growth and division of cells
- helps control big3 blood cells

→ mutation

  • increases production and prolongs survival
  • erythroid progenitor offspring do not need** (=unusual) **erythropoietin
    → avoids apoptosis // erythropoietin levels low
  • overproduction of cytokines: increases inflammation
147
Q

Major criteria Polycythaemia Vera

A
  • complete blood count with differential

→ high RBC = diagnose

→ high WCC and platelets = distinguish PV from secondary causes

  • presence of JAK2 mutation on genetic screen
148
Q

Minor criteria Polycythaemia Vera

A
  • bone marrow biopsy: prominent erythroid, granulocytic & megakaryocytic proliferation
  • serum erythropoietin low
149
Q

Treatment goals Polycythaemia Vera

A

→ no cure, aims to maintain normal blood count

150
Q

Treatment plan Polycythaemia Vera

A

venesection = symptom relief
lower PCV and platelet count, 400-500ml/week
often sole tx

chemo
intolerant to venesection / uncontrolled others e.g. thrombocytosis
- hydroxycarbamide and low dose bulsulfan

  • *low dose aspirin** alongside above
  • radioactive phosphorus but only in over 70 due to + risk of acute leukaemia
  • allopurinol to block uric acid production thereby reducing gout / tumor lysis
  • lifestyle - smoke, cardio health
151
Q

What is thrombocytosis aka thrombocythaemia?

A

= platelet count above the normal range = 450 x 10^9 / L in adults
cythaemia = result of proliferation of megakaryocytic cell line

152
Q

How to differentiate thrombocytosis from polycythaemia vera?

A

besides a raised platelet, check if hematocrit is also raised - if yes → polycythaemia vera

153
Q

types of thrombocytosis / thrombocythaemia?

A

→ Primary = essential
= JAK2 mutation (others: MPL / CALR gene)
= autonomous production

→ Secondary = reactive
= caused by conditions
= triggers release of cytokines → mediate an increase in platelet production
= TUC then transient

154
Q

Presentation thrombocytosis / thrombocythaemia?
- what are thrombus symptoms? (4)

A

thrombus symptoms
DVT // Pulmonary embolism // MI from clot // Stroke or TIA

Other symptoms

  • fatigue, weight loss, low grade fevers, night sweats
  • *erythromelalgia**: pain, redness and swelling in hands or feet
  • *enlarged spleen**
155
Q

investigations for thrombocytosis / thrombocythaemia?

A
  1. platelet count raised - from blood count
  2. review blood film, acute phase reactants, iron status
156
Q

Possible outcomes from investigations for thrombocytosis / thrombocythaemia?

A
  • reactive thrombocytosis
  • essential thrombocytosis
  • iron deficiency
157
Q

Based on investigations for thrombocytosis, if everything is normal but with symptoms: - what to do next
- if symptoms persist with no explanation?

A
  • if normal: repeat blood count
  • if persistent unexplained thrombocytosis: molecular genetics screen for JAK2, CALR, MPL. Diagnose if fulfils criteria
158
Q

Based on investigations for thrombocytosis, if it’s iron deficiency?

A

treat iron deficiency ( replace iron → oral is preferred (safer), IV is no faster than oral! - ferrous sulphate 200mg 1-3x daily) then repeat blood count

159
Q

If Acute Phase response (??)

A

Diagnose as reactive thrombocytosis

160
Q

Diagnostic criteria for Essential Thrombocythaemia?

A

4M or 1-3M + m

  • *Major**
    1. platelet count ≥ 450x10^9 / l
    2. bone marrow biopsy showing increased megakaryocytes (forms platelets) with abnormal nuclei
    3. exclusion of other diseases, e.g philly+ CML, PV, myelofibrosis, myelodysplastic syndromes, m - neoplasms
    4. presence of JAK2, CALR, or MPL mutation

Minor
Presence of clonal marker (chromosome abnormality) or NO evidence that disorder is caused by reactive thrombocytosis

161
Q

Treatment goals thrombocytosis / thrombocythaemia?

A

→ prevent thrombosis = main goal!
→ anyone with venous blood clot will require lifelong treatment with anticoag

162
Q

Treatment plan for thrombocytosis / thrombocythaemia based on risk category? (4)

A
  • *Very low**
  • under 60, no thrombo, no JAK2 mut
  • observation only
  • *Low**
  • under 60, no thrombo, no JAK2 mut
  • low dose aspirin
  • *Intermediate**
  • over 60, no thrombo, no JAK2 mut
  • low dose aspirin with or without cytoreductive therapy
  • *High**
  • over 60, yes thrombo, yes JAK2 mut
  • low dose aspirin with cytoreductive therapy
163
Q

Medications for thrombocytosis / thrombocythaemia? (1+2+emerg)

A
  • *Aspirin**
  • low dose: 80-100mg per day
  • reduces clotting and complications
  • SE = GI upset and heartburn

first line = Hydroxycarbamide (hydroxyurea)

  • decrease number of blood cells made in the bone marrow
  • succeeds in decreasing in weeks, minimal and short term SE
  • SE: low white blood cell count, nausea, vomiting, diarrhoea and oral ulcers

second line - bulsulfan (chemo!)

  • used in older patients who are resistant or intolerant to hydroxyurea
  • SE low counts, nausea and vomiting, diarrhoea, poor appetite and mouth sores
  • *emergency - plateletpheresis**
  • circular patient-machine cycle where machine collects platelets, returning the rest to patient’s blood strea
  • temporary effect! only used for emergencies e.g. clotting complications
164
Q

Complications thrombocytosis / thrombocythaemia?

A
  • myelofibrosis
  • less common - myelodyplastic syndrome or acute myeloid leukemia
165
Q

What is Idiopathic Thrombocytopenic Purpura (ITP)?

A

= Immune thrombocytosis
= easy or excessive bruising and bleeding from unusually low level of platelets

166
Q

What is petechiae?

A

superficial bleeding into skin that appears as pinpoint sized reddish-purple spots

167
Q

Purpura vs petechiae?

A

Petechiae are very small, pinpoint sized reddish purple spots less than 4 millimeters (mm) in size.

Purpura are larger areas of bleeding under the skin, typically between 4 mm and 10 mm

168
Q

Signs & symptoms for Idiopathic Thrombocytopenic Purpura (ITP)

A
  • easy or excessive bruising
  • petechiae / purpura
  • bleeding from gum & nose
  • blood in urine or stools
  • unusually heavy menstrual flow
169
Q

Acute causes for Idiopathic Thrombocytopenic Purpura (ITP)

A
  • esp in children
  • history or recent viral infection → may be immunisation!
  • varicella zoster (chickenpox) or measles
  • flu
  • present as muco-cutaneous bleeding!
  • may be severe but rarely life-threatening
  • sudden self limiting purpura → red or purple spots on skin
170
Q

Chronic causes for Idiopathic Thrombocytopenic Purpura (ITP)

A
  • less acute than children’s
  • most commonly in women - may be associated with other autoimmune disorders
  • chronic lymphocytic leukaemia (CLL), SLE, thyroid disease & autoimmune haemolytic anaemia
  • from infection
  • HIV, hep, H pylori (causes stomach ulcers)
  • platelet autoantibodies detected in 60-70% of patients
171
Q

Investigations and criteria for diagnosis - Idiopathic Thrombocytopenic Purpura (ITP)

A
  • bone marrow exam
  • thrombocytopenia shown
  • with increased or normal megakaryocytes in marrow
  • platelet autoantibody - present in 60-70% but not needed to diagnose
172
Q

Medications for Idiopathic Thrombocytopenic Purpura (ITP) - (2)

A
  • mild - regular monitoring and platelet checks. children mostly improves without treatment.

First line - **corticosteroids e.g. prednisolone**
- IV immunoglobulin e.g. IV IgG - raises platelet count more rapidly than steroids thus useful for surgery

Second line - **splenectomy**

  • eliminates source of platelet destruction
  • increases susceptibility to infection
  • if splenectomy fails then immunosuppression e.g. oral or IV azathioprine

Others:
rituximab: increases platelet count as an immunosuppressant, but may reduce effectiveness of vaccine

173
Q

What is Thrombotic Thrombocytopenia Purpura (TTP)

A

→ this is quite rare
= widespread adhesion and aggregation of platelets leading to microvascular thrombosis; thus profound consumption of platelets and thrombocytopenia

174
Q

Causes for Thrombotic Thrombocytopenia Purpura (TTP)

A
  • acquired (idiopathic) and congenital (familial)
  • lack of ADAMTS 13 enzyme
  • responsible for breaking down large strings of VWF into smaller units, which reduces the small blood vessel clots
  • often stops working because body makes antibodies to it
  • cancer, pregnancy, drug induced - quinine
175
Q

Risk for Thrombotic Thrombocytopenia Purpura (TTP)

A
  • women more than men
  • peak in 40’s
176
Q

Presentation - Thrombotic Thrombocytopenia Purpura (TTP)

A
  • florid purpura - discolouration of the skin or mucous membranes due to haemorrhage from small blood vessels
  • fluctuating cerebral dysfunction
  • headaches, mental changes, confusion, speech abnormalities, slight or partial paralysis, seizures or coma
  • **haemolytic anaemia** with red cell fragmentation, often accompanied by acute kidney injury
  • fever
  • blood plasma protein and small number of RBC in urine may also occur
177
Q

Diagnosis - Thrombotic Thrombocytopenia Purpura (TTP)

A
  • blood test and film
  • coag screen is normal
  • lactate dehydrogenase is raised as a result of haemolysis
  • in about half: increased creatinine
  • **ADAMTS13** level check
178
Q

Treatment for Thrombotic Thrombocytopenia Purpura (TTP)

A
  • plasma exchange
  • tablets or drip
  • IV rituximab
  • IV methylprednisolone
179
Q

What is Myelofibrosis

A

= blood cancer characterised by the buildup of scar tissue = fibrosis in the bone marrow

→ bone marrow cannot make enough healthy blood cells so spleen and liver compensates through cell making and increase in size

180
Q

Types of myelofibrosis

A
  • primary
  • as a JAK mutation
  • secondary - as a result of PV or ET - 10-20%
  • complication - acute myeloid leukemia, portal hypertension (from cell production), extramedullary hematopoiesis (production of BC), gout
181
Q

3 major symptoms of myelofibrosis

A
  • usually slow developing and does not cause symptoms early on

→ **not enough blood cell symptoms**

  • Fatigue, weakness, shortness of breath, or pale skin
  • Frequent infections due to a low white blood cell count
  • Bleeding or bruising easily due to a low platelet count

→ **splenomegaly / hepatomegaly (liver)**
- abdominal pain, feeling of fullness, decreased appetite, weight loss

→ **general**

  • early satiety / cachexia
  • night sweats
  • itchy skin
  • problems concentrating
  • fever, bone or joint pain
  • weight loss
182
Q

Investigations for Myelofibrosis

A
  • FBC & blood film
  • leucoerythroblastic =
  • tear drop poikilocytes
  • normal b12 / folate / ferritin
  • ultrasound (enlarge of spleen or liver)
  • bone marrow biopsy
183
Q

Diagnosis criteria for myelofibrosis

A

at least 3M + 1m!!

  • *major**
    1. typical megakeryocyte changes accompanied by ≥ grade 2 reticulin / collagen fibrosis
    2. presence of JAK2, CALR, MPL mutations or others; or rule out reactive bone marrow fibrosis
    3. no other myeloid neoplasms
  • *minor**
    1. anemia not otherwise explained
    2. leukocytosis ≥ 11x10^9
    3. palpable splenomegaly
    4. increased serum lactate dehydrogenase (LDH)
    5. leukoerythroblastic blood smear
184
Q

Differential Diagnosis for myelofibrosis

A
  • lactate dehydrogenase - (association found - raised for myeloproliferative diseases)
  • b12 / folate / ferritin (normal)
  • hep B / c / HIV (rule out!)
185
Q

Treatment principle for myelofibrosis

A

→ depends on prognostic scoring: Dynamic International Prognostic Scoring System (DIPSS), IPSS, DIPSS plus, MIPSS-70

186
Q

Danazol - what is it and what are the SEs?

A
  • androgen drug, help increase RBC production
187
Q

Hydroxyurea - what is it and what are the SEs?

A
  • chemo drug, reduce spleen size or high platelet & WBC count in those not eligible for others
  • SE low count (+ infection & bleeding), nausea, vomitting, diarrhea & oral ulcers
188
Q

Ruxolitinib - what is it and what are the SEs?

A
  • JAK 1 /2 inhibitor.
  • for Pri MF, Post PV MF, Post ET-MF.
  • SE low counts, bruising, dizziness and headaches. major tox. increase risk of infections
189
Q

Prenisolone - what is it and what are the SEs?

A
  • corticosteroid
  • mainly used for ITP, also for other inflammatory diseases e.g. Crohn’s & arthritis
190
Q

Treatment plan for myelofibrosis

A
  • Depend on prognostic scoring system

**Very low risk**
- no symptoms: no anaemia / enlarged spleen / comp’s = generally not treated

**Low risk**
- some symptoms: may be observational or cytoreductive treatment for symptom relief

**Intermediate risk**
- INT-1 risk with symptoms
→ Ruxolitinib
→ allogeneic stem cell transplant

  • INT-2 with symptoms
    → Ruxolitinib
    → Fedratinib
    → Allogeneic stem cell transplant
    → treatment for anemia

**High Risk** = depend on classification, see above

191
Q

Allogenic stem cell transplant - what is it and what are the SEs?

A
  • high dose of chemo to kill off abnormal, but will also kill off normal
  • infusion of blood stem cells and replace defective cells
  • creates new immune system
  • high SE and mortality
  • Comp: GVHD
192
Q

Fedratinib - what is it and what are its side effects?

A
  • kinase inhibitor with activity against JAK2 and FLT3, thereby reducing the abnormal production of blood cells and associated symptoms.
  • for Prim MF, post-PV MF, or post-essential thrombocythaemia myelofibrosis
  • SE nausea very common (counter w/antiemetics), constip, diarr, vom, HT, headache, infect, pain
193
Q

Drugs for splenomegaly

A
  • hydroxyurea
  • ruxolitinib
  • Splenectomy - not med lol
194
Q

Identify the rash on picture?

(& name the possible condition?)

A

Purpura

idiopathic thrombocytopenic purpura ITP

195
Q

Identify the rash in picture

(and name the possible condition?)

A

petechiae

idiopathic thrombocytopenic purpura

196
Q

Diagnosis based on the following presentation?

  • spikey paraprotein
  • high Ca > 0.25mmol/l above limit
  • renal impairment, creatine > 173 mmol/l
  • anaemia
  • bone disease
A

multiple myeloma

197
Q

What is multiple myeloma?

A
  • cancer of differentiated b-lymphocytes, known as plasma cells
  • a bone marrow cancer, leads to progressive bone marrow failure
  • characteristic spikey paraprotein production
  • incurable
198
Q

on the characteristic spikey protein

  • produced by?
  • type of protein?
  • how to determine which type?
A

paraprotein

  • produced by myeloma cells
  • immunoglobulins - usually IgG (70) or IgA (30), others rare
  • serum electrophoresis / densitometry
199
Q

Specific presentations of multiple myeloma?

A

Spikey = paraprotein = immunoglobulin

Old = average age of incidence is 70

C = high Ca, > 2.75 mmol/l

R = renal imapirment, creatine >173 mmol/l

A = anaemia, ?

B = bone disease - lytic lesions, osteoporosis, spinal cord compression

200
Q

Diagnostic threshold of paraproteins for multiple myeloma?

A

> 30g / dl !

201
Q

Other possible presentation of multiple myeloma besides spikey old crab?

A

hyperviscosity

recurrent infection > 2 episodes in past 2 years

amyloid

raised ESR

& globulin frequent signals

202
Q

Diagnosis based on the following presentations?

  • paraproteins are an incidental finding, < 30g / dl
  • < 10% plasma cells in bone marrow
  • no related organ or tissue damage
  • no evidence of amyloid or other lymphoproliferative disorder (LPD)
A

Monoclonal gammopathy of undetermined significance (MGUS)

  • thought to be preceeding myeloma
203
Q

Subtypes of myeloma (2) and how would you treat?

A
  • *Smouldering myeloma** = >30g/l paraprotin and >10% plasma cells in BM, but no related organ or tissue impairment
  • 20% risk of progression to MM 1st year

Symptomatic myeloma = hits diagnostic criteria and/or ROTI and/or tissue amyloid

Only treat symptomatic myelomas

204
Q

Investigations for Multiple Myeloma?

A

Main

  • bone marrow biopsy
  • serum electrophoresis (where densitometry is a step)
  • FBC for renal function, UE (serum calcium)
  • urine

Others

  • imaging is MRI
205
Q

Treatment principles and options for Multiple Myeloma

A

P__rinciple:

  • control and live with as incurable.
  • reduce number of cells, reduce symptoms and complications

Options

  • Bisphosphonates: Aledronic acid (for those potentially osteo frag frac), pamidronate, zoledronic acid (for hypercalcaemia)
  • CI renal impairment, SE oseophagitis, osteonecrosis in jaw, non healing lesions
  • generic chemo
  • stem cell transplant
206
Q

Options of generic chemo for multiple myeloma? (5)

A
  • monoclonal antibodies
  • immunomodulatory drugs (thalidomide & analogues SE birth defects)
  • corticosteroids - reduce most cancers
  • alkylating agents
  • proteasome inhibitors
207
Q

Briefly describe the stem cell transplant process?

A
  • stem cell harvested
  • high dose melphalan
  • stem cell transplant
  • is a chronotoxic procedure but keeps disease away for longer
  • SE infection
208
Q

What are amyloids?

A

Proteins of an abnormal shape which deposits into tissues

stains blue with iodine

209
Q

What is systemic amyloidosis?

A

Tissue damage from extra amyloid deposits

can occur as a result of multiple myeloma

210
Q

Symptoms of systemic amyloidosis?

A

Nephrotic syndrome ± renal impairment, congestive cardiomyopathy, neuropathy

bleeding, raccoon eyes & microglossia

211
Q

Investigations for systemic amyloidosis?

A

proteinuria, hypoalbuminuria

biopsy of the tissues

212
Q

Treatment for systemic amyloidosis?

A

No cure, cannot remove amyloid from organs :(

Organ transplant if needed.
Treat multiple myeloma

213
Q

What is a lymphoma & how are they classified?

A

Haem malignancy arising from lymphoid tissue / cells

Commonly categorised as Hodgkin and non-Hodgkin lymphoma

(= WBC cancer)

214
Q

What is the difference between Hodgkin and non-Hodgkin lymphoma

A

Presence of Hodgkin / Reed Sternberg cells

215
Q

Besides Hodgkin & Non-Hodgkin, how else are lymphoma classified?

A

according to cells of origin

B cell = more common
or NK/T cell

216
Q

How might you differentiate Hodgkin’s from non-Hodgkin’s lymphoma?

A

Hodgkin = bimodal, 20’s & 60’s
Non Hodgkin = 50’s

Hodgkin also has pruritus & alcohol triggered pain

217
Q

What are Hodgkin/Reed-Sternberg cells (HRS) like?

A

Hodgkin = mononucleated

Reed-Sternberg = multinucleated, like an owl

218
Q

Presentations for Hodgkin’s lymphomas?

A

Lymphadenopathy = typically painless, firm, enlarged lymph nodes in the neck

B symptoms = fever, night sweats & weight loss

Pruritus = differentiate from non-H!!!

Mediastinal mass / hepatosplenomegaly, malaise, fatigue

219
Q

How might you diagnose a Hodgkin’s lymphoma?

A

Lymph node scans

Blood smear / FBC

Skin biopsy

biopsy of lymph nodes
fine needle aspiration, core biopsy or excision

220
Q

What would the blood picture be like if there was bone marrow involvement?

A

high WBC
low haemo & platelets

bone marrow biopsy if needed

221
Q

How might you stage a Hodgkin’s lymphoma?

A

Lugano system = for HL!

limited = single / group of adjacenet / 2 or more same side

Stage II bulky = II with bulky disease

Advanced = nodes on both sides, above diaphragm with spleen

222
Q

Methods used in staging of Hodgkin’s lymphoma?

A

CT scans

Bloods, bone marrow

extranodal involvement / B symptoms

223
Q

Main treatment for Hodgkin’s Lymphoma?

A

ABVD Chemo (4x chemo agents)

A = Doxorubicin

B = Bleomycin
inhibit DNA synthesis

V = Vinblastine
inhibit microtubule formation

D = Dacarbazine

224
Q

Other tx options & support for Hodgkin’s Lymphoma?

A

Monoclonal antibodies
esp anti CD20 = rituximab etc

Blood transfusions = irradiated blood
avoid graft-vs-host disease

225
Q

Prognosis for HL?

A

75% cured, and minimum survival for all stages = about 5 years

226
Q

Presentation for Non-Hodgkin lymphoma?

A

More common than Hodgkin’s!

50’s

may present with only one system

227
Q

Main treatment for non-Hodgkin’s lymphoma?

A

R-CHOP Chemo

R - Rituximab (CD20)

C - Cyclophosphamide
= inhibit DNA Synthesis

Doxorubicin
= inhibit topoisomerase II = DNA synthesis

Vincristine
= inhibit microtubule formation to tubulin

Prednisolone

228
Q

Most common form of Non Hodgkin’s Lymphoma?

A

Diffuse large B cell lymphoma

229
Q

Presentation for DLBCL?

A

Rapidly enlarging mass, commonly in the neck, abdomen or mediastinum

B symptoms in a third of patients

may lead to superior vena cavae obstruction & cord compression

230
Q

2nd most common form of B cell NHL?

Presentation?

A

Follicular lymphoma

85% have a translocation
between chromosome 14 and 18

Gradually worsening, painless lymphadenopathy

231
Q

What is a Burkitt’s lymphoma?

A

high grade, rapidly proliferating B cell NHL

commonly affects children

232
Q

Subtypes / causes of Burkitt’s lymphoma?

A

Endemic = Epstein-Barr virus
follows distribution of malaria

Sporadic

Immunodeficiency = AIDs / immunosuppressive meds

233
Q

Presentation - Burkitt’s lymphoma?

A

rapidly enlarging tumour
in jaw of a child

alt: enlarged lymph nodes, abdo mass

GI pres common e.g. bowel obstruction

fever, weight loss & night sweats

234
Q

What is superior vena cava obstruction? How will it present?

A

dyspnoea, face swelling, head fullness

cyanosis, stridor, upper limb oedema, distended neck and chest wall veins

symptoms exacerbated by bending forwards / lying down

235
Q

Tests for SVC obstrustion?

A

Pemberton’s sign
patient asked to elevate both arms above head for 1-2min
positive if causes cyanosis, respiratory distress or congestion

Chest CT = diagnostic!!

236
Q

Tx SVCO?

A

Stent if stridor

Get help!

237
Q

What is tumour lysis syndrome?

A

metabolic disturbances arising from the breakdown of malignant cells following the initiation of treatment for malignancy

238
Q

How might tumour lysis syndrome present?

A

fluid overload
haematuria
tetany & paraesthesia
bronchospasm

AKI! from uric acid & calcium phosphate in renal tubules
esp if using allopurinol & rasburicase

239
Q

Tests for TLS?

A

Electrolytes, Serum urate, Renal function
= essential

ECG monitor, additional as need

240
Q

What is a TLS diagnosis based on?

A

increases in uric acid, potassium, phosphate & calcium levels

alt - serum creatinine +, cardiac arrhythmia, seizure which cannot be tagged to a med

(25% increase each)

241
Q

Prevent and treat TLS?

A

Allopurinol = xanthine oxidase
= prophylactic only

Rasburicase = recombinant uric oxidase = treat + prophy

Supportive as needed

Phase 2A (12 decks)

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