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Haem / Onc Flashcards

1
Q

give 3 causes of microcytic anaemia

A 
TICS
Thalassaemia
Iron-deficiency 
Chronic disease (20% will be microcytic)
Sideroblastic anaemia.
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2
Q

give 3 causes of normocytic anaemia

A
  • bleeding
  • anaemia of chronic disease (80% is normocytic)
  • bone marrow failure; - renal failure (decreased erythropoietin)
  • hypothyroidism
  • haemolytic anaemia
  • pregnancy
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3
Q

give 3 general symptoms of anaemia

A

classic = fatigue, dyspnoea, faintness

+ palpitations, headache, tinnitus, anorexia

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4
Q

give 3 general signs of anaemia

A

classic = conjunctival pallor

pallor, tachycardia

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5
Q

give a physiological cause of anaemia

A

pregnancy (normocytic)

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6
Q

give some causes of iron-deficiency anaemia

A
  • inadequate intake: poor diet, poverty
  • poor absorption: poor acid production, gastric surgery, coeliac
  • excessive loss: GI bleeding, peptic ulcers (NSAID use), diverticulosis, neoplasm, menorrhagia
  • increase requirement: infancy, pregnancy, hookworm
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7
Q

describe what is seen on a peripheral blood film in iron-deficiency anaemia

A

microcytic hypochromic RBCs, varying in size and shape (anisocytosis and poikilocytosis)

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8
Q

possible presenting features of iron deficiency anaemia?

A

koilonychias (spoon nails)
mouth changes - angular stomatitis, atrophic glossitis
fatigue, pallor, faintness, dyspnoea
pica (classic = ice craving)

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9
Q

In iron deficiency anaemia, what will happen to the iron, ferritin and total iron binding capacity (TIBC) (aka iron studies)?

A

iron and ferritin are decreased.
TIBC is increased.
transferrin saturation = low.

NB - ferritin is acute phase protein so may be raised in inflammation/infection/malignancy

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10
Q

how would you treat iron deficiency anaemia? how long would this treatment be given?

A

oral ferrous sulphate - given until anaemia resolved + further 3-6/12

consider transfusion if symptomatic at rest w/ dyspnoea and chest pain.

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11
Q

what are some side effects of ferrous sulphate?

A

nausea, abdominal discomfort, diarrhoea/constipation, black stools

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12
Q

what diagnostic tests would you perform if you suspected anaemia?

A

blood count and film (Hb, haematocrit, MCV, MCHC, peripheral blood smear).
iron studies, B12 etc.

tests for cause e.g. coeliac serology, endoscopy etc if IDA.

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13
Q

how would you treat anaemia of chronic disease?

A

treat underlying disease.

give Epo.

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14
Q

what is sideroblastic anaemia?

A

think of it as microcytic hypochromic anaemia that doesn’t respond to iron.

inherited or acquired disorder - body has enough iron but can’t incorporate it into Hb (ineffective erythopoeisis).

iron absorption is increased.

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15
Q

investigations for sideroblastic anaemia?

A

microcytic hypochromic anaemia.
blood film = dimorphic population of normal and hypochromic red blood cells.
iron studies: serum iron high, serum ferritin high, TIBC low.

marrow aspirate = presence of sideroblasts - “perinuclear ring of iron granules with Prussian Blue staining”

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16
Q

how would you treat sideroblastic anaemia?

A

mostly supportive.
iron chelation - desferrioxamine.

repeated RBC transfusions if needed.
avoid alcohol + vit C (they increase iron absorption).

if hereditary - consider Pyridoxine (vit B6).

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17
Q

give 3 causes of sideroblastic anaemia.

A
  • inherited (XLSA - X-linked)
  • myelodysplastic syndrome (MDS)
  • myeloma
  • PRV
  • pyridoxine (B6) deficiency
  • drugs (isoniazid)
  • alcohol misuse
  • lead toxicity.
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18
Q

what causes pernicious anaemia?

A

autoimmune atrophic gastritis - autoantibodies against parietal cells and intrinsic factor, so these are destroyed leading to achlorydia and B12 malabsorption.

associated with other AI disease - thyroid, vitiligo, DM.

risk of gastric cancer.

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19
Q

how does B12/folate deficiency lead to anaemia?

A

B12 and folate needed for DNA synthesis - developing red cells can’t divide, they are stuck as large immature cells (megaloblastic) which then become macrocytic RBCs

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20
Q

what signs characterise pernicious anaemia?

A

mild jaundice due to haemolysis - pallor + jaundice = “lemon tinged skin” is classic.

headache is hallmark of megaloblastic anaemia.

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21
Q

what specific tests would you perform if you suspected pernicious anaemia?

A

FBC, blood film etc and:

  • intrinsic factor antibody
  • antiparietal cell antibody (90% sensitive, but not specific as elevated in atrophic gastritis)
  • Schilling test (radiolabelled B12)
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22
Q

give some causes of folate deficiency

A

poor diet.
increased demand - pregnancy or increased cell turnover.
malabsorption (coeliac)
drugs, alcohol, MTX (inhibits folic acid synth).

folate present in green veg, nuts, liver.

get macrocytic anaemia but NO neurological signs - B12 deficiency you also get peripheral neuropathy and neuropsych issues.

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23
Q

how would you investigate and treat folate-deficiency anaemia?

A

blood film shows macrocytic RBCs, hypersegmented neutrophils.
do other anaemia bloods.

oral folic acid (1-5mg) + B12 for 4 months min. treat cause.

if pancytopaenia present as well consider packed RBC transfusion.

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24
Q

give some acquired causes of haemolytic anaemia

A

Immune mediated:
- due to autoantibodies and direct antiglobulin +ve (Coombs’ positive), often part of another autoimmune condition (SLE, scleroderma etc).

Non-immune mediated:

  • direct antiglobulin (Coombs) negative
  • infection e.g. hep B and C, malaria
  • microangiopathic haemolytic anaemia - HUS, TTP, DIC
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25
Q

give some hereditary causes of haemolytic anaemia

A
  • Enzyme defects - G6PD deficiency, pyruvate kinase deficiency
  • Membrane defects - hereditary spherocytosis, elliptocytosis
  • Abnormal Hb production - sickle cell disease, thalassaemia
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26
Q

what is aplastic anaemia?

A

anaemia due to bone marrow failure
triad = pancytopenia with hypoplastic marrow and no abnormal cells
marrow stops making all cells

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27
Q

give some causes of aplastic anaemia

A

major associations = pregnancy, coeliac, SLE

acquired causes:

  • idiopathic (50%)
  • drug/toxin exposure (NSAIDs, penicillamine, gold)
  • post viral (esp hep)

inherited causes:

  • Fanconi anaemia (AR)
  • Shwachman-Diamond syndrome (AR)
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28
Q

give 2 specific features of aplastic anaemia

A

bruising with minimal trauma.
blood blisters in mouth.

presents with neutropenia (infections), anaemia symps and thrombocytopaenia (bleeding and bruising)

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29
Q

what test would you perform in aplastic anaemia? what would it show?

A

bone marrow biopsy - hypocellular marrow with increased fatty spaces. no abnormal cell population

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30
Q

how would you treat aplastic anaemia?

A

if asymptomatic - give neutropenic regimen.

if severe - matched related allogenic marrow transplant (can be curative) + RBC and Plt transfusion + abx.

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31
Q

what is sickle cell anaemia?

A

autosomal recessive disorder causing production of abnormal beta globin chains.
HbSS/HbAS instead of HbA (HbAS is carrier state)

sickle shaped cells disrupt the blood cell, haemolyse earlier and causes varying degrees of anaemia.
obstruction of small blood capillaries leads to painful crises, organ damage and increased vulnerability to infection

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32
Q

being a carrier of sickle cell protects you against what disease?

A

falciparum malaria

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33
Q

what is the pathogenesis of sickle cell anaemia?

A

HbS polymerizes if hypoxia/acidosis causing RBCs to sickle - rigid, fragile cells that occlude small vessels and have short lifespan (haemolyse).

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34
Q

describe the clinical features of vaso-occlusive crises seen in sickle-cell anaemia

A

severe pain due to effect on marrow of microvascular occlusion. acutely painful hands and feet.
dactylitis. visual floaters. chest/abdo pain (mesenteric ischaemia). chronic renal failure.
avascular necrosis femoral head/bone infarcts.

general symps/signs - parent with sickle cell anaemia/trait. symps of anaemia + haemolysis = jaundice, pallor, lethargy, tachycardia.

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35
Q

what is splenic sequestration?

A

a type of sickle-cell crisis:
vaso-occlusion produces acute painful enlargement of spleen.
pooling of RBCs in spleen = hypovolaemia = circulatory collapse and death.
immediate transfusion needed.

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36
Q

give 3 long-term complications of sickle-cell disease

A

poor growth, bone problems, infections, leg ulcers, neurological complication, gallstones, retinal disease, lung fibrosis, pulmonary hypertension

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37
Q

what tests would you perform in a case of sickle cell disease? what would you see?

A

FBC. - low Hb.
blood film - sickle cells and target cells (pale centre). Howell-Jolly bodies.
sickle solubility test - HbSS/HbAS instead of HbA
Hb electrophoresis - distinguishes HbSS and HbAS.

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38
Q

how would you treat sickle cell disease?

A

aim to diagnose at birth via screening (newborn blood spot).

pneumococcal vaccine + penicillin prophylactically + genetic counselling + parental education.
hydroxyurea (need monthly blood tests) - increases HbF production.
repeat blood transfusions if needed.

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39
Q

describe the genetics of beta thalassaemia

A

mutations in beta-globin genes (chromosome 11) leading to no/reduced beta chain production (either beta0 or beta+).

seen in individuals of mediterranean, africa, or SE asian descent.
mainly autosomal recessive, but might still report family hx.

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40
Q

how does beta thalassaemia cause anaemia?

A

decreased/absent synthesis of beta-globin leads to excess alpha production + membrane damage/cell destruction.
get ineffective erythropoeisis and increased haemolysis.

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41
Q

what are the features of minor beta thalassaemia?

A

symptomless carrier state. mild anaemia. hypochromic and microcytic. often gets muddled with IDA.
beta/beta+ or beta/beta0

(silent carrier has normal haem parameters)

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42
Q

what are the features of medium (aka intermediate) beta thalassaemia?

A

presents similarly to major but as a toddler rather than in first year.

beta+/beta+ or beta0/beta+
doesn’t require transfusions.

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43
Q

what are the features of major beta thalassaemia?

A

severe anaemia - needs regular transfusions.

presents in 1st year with progressive pallor, abdo distension (hepatosplenomegaly) and characteristic head shape (skull bossing), failure to thrive.
beta0/beta0

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44
Q

how would you treat beta thalassaemia?

A

1) minor/trait = genetic counselling, iron advice (avoid unless deficient)
2) medium = genetic counselling, transfusion if symptomatic anaemia (e.g. infection, periop) + iron monitoring with chelation (desferrioxamine)

3) major = genetic counselling + regular transfusion to >10g/dL + iron monitoring with chelation.
± splenectomy
± assess for haematopoeitic stem cell transplant (curative)

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45
Q

what are the genetics of alpha thalassaemia?

A

gene deletions (not point mutations as in beta) in alpha globin chain genes on chromosome 16.

decreased/absent synthesis of alpha globin –> excess beta production —> ineffective erythropoeisis –> anaemia and haemolysis.

mainly autosomal recessive.
sub-saharan africa + middle east + SE asia - corresponds to malaria distribution.

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46
Q

describe the features of a 4+ gene deletion alpha thalassaemia

A

aka major alpha thalassaemia or Bart Hydrops Fetalis.

no alpha chains synthesised.
death in utero.

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47
Q

describe the features of a 3 gene deletion alpha thalassaemia

A

leads to beta tetramers, which are detected on electrophoresis.
aka HbH disease.

moderate anaemia symptoms and splenomegaly, jaundice/gallstones.
may present in childhood (more severe), with family history, from the right geographical areas.

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48
Q

describe the features of a 2 gene deletion alpha thalassaemia

A

alpha thalassaemia trait.

microcytosis ± mild anaemia - mixed up with IDA a lot.

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49
Q

how many alpha globin gene deletions may a patient have and still appear clinically normal?

A

1 - and would be silent carrier.

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50
Q

what is glucose-6-phosphate dehydrogenase (G6PD) deficiency?

A

X linked haemolytic condition caused by mutation in the G6PD gene leading to G6PD enzyme deficiency.
common in parts where malaria is common as it’s protective!

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51
Q

what does G6PD do?

A

catalyses step one of pentose phosphate pathway (similar glycolysis) which generates NADPH (important for red cells to protect from oxidative stress) - protects RBC membrane from damage

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52
Q

does G6PD deficiency affect mainly men or women?

A

men

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53
Q

give some precipitants of G6PD deficiency crises

A

henna.
favism (ingesting fava/broad beans).
drugs (cephalosporins), infections.

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54
Q

what are the features of an acute G6PD deficiency haemolytic episode?

A

anaemia, fever, jaundice, dark urine (suggests intravascular haemolysis).
N&V, dehydration, AKI (due to haemoglobin precipitates).

bite and blister cells, Heinz bodies on blood film

OR - may present as prolonged neonatal jaundice rather than linked to acute eps/triggers.

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55
Q

what is polycythaemia?

A

an increase in Hb, PCV - packed cell volume (haematocrit) - or RCC (red cell count)
PCV = % by volume of RBCs in blood

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56
Q

what is the difference between relative and absolute polycythaemia?

A 
relative = low plasma volume, but no change in cell numbers.
absolute = increase in RBC mass.
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57
Q

who gets relative polycythaemia?

A

middle aged obese males, smokers, high alcohol intake, hypertension

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58
Q

what causes primary polycythaemia?

A

polycythaemia rubra vera - malignant proliferation of a clone from one pluripotent marrow stem cell - myeloproliferative disorder of predominantly red cells.

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59
Q

what causes secondary polycythaemia?

A

due to hypoxia - high altitudes, chronic lung disease, heavy smoking

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60
Q

what gene mutation causes polycythaemia rubra vera?

A

JAK2 - V617F somatic mutation.

Ph negative.

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61
Q

In polycythaemia rubra vera, what is there an excess proliferation of?

A

red cells, white cells and platelets - hyperviscosity/hypervolaemia.

it’s a clonal haematopoietic disorder w/ erythrocytosis, thrombocytosis, leucocytosis + splenomegaly.

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62
Q

give 3 symptoms of polycythaemia

A

headache, dizziness, tinnitus, visual disturbance, itching/pain/redness of extremitites after warm bath, burning in fingers and toes. plethoric appearance (red and full).

features of thrombosis/bleeding e.g. stroke, PE, MI, DVT etc

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63
Q

give 3 things you might find on examination in polycythaemia

A

facial plethora (red, turgid face), splenomegaly (only in PRV), gout, arterial/venous thrombosis

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64
Q

why do polycythaemia patients get gout?

A

increased urate from RBC turnover

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65
Q

what will the marrow of a patient with polycythaemia rubra vera show? other Ix for PRV?

A

hypercellularity with erythroid hyperplasia - “trilineage growth”

other Ix:

  • chromium studies = elevated RBC mass
  • RBC shows raised Hb, raised haematocrit, raised WBC, raised plts.
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66
Q

how would you treat polycythaemia rubra vera?

A

Rx aims to keep low haematocrit + reduce risk of thrombosis.

  • venesection
  • hydroxycarbamide (cytoreduction, used if high risk)
  • low dose aspirin (75mg)
  • manage CV RFs
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67
Q

how would you treat secondary polycythaemia?

A

treat primary cause.

oxygen therapy + smoking cessation.

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68
Q

list 4 risk factors of DVT

A

increasing age, pregnancy, synthetic oestrogens (pill, HRT), trauma, surgery, past DVT, cancer, obesity, immobility, thrombophilia

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69
Q

what other disease may a DVT present as?

A

pulmonary embolism

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70
Q

describe the clinical features of a DVT

A

warm, tender calf, with erythema. fever. pitting oedema.

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71
Q

what investigations would you do on a patient with a suspected DVT?

A

D-dimer - -ve result excludes DVT, +ve doesn’t mean it is DVT.
doppler US.

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72
Q

give 4 features included in the Wells score

A

active cancer, immobility, major surgery in last 4 weeks, local tenderness, swollen leg, pitting oedema, collateral superficial veins

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73
Q

how would you manage a patient with a DVT?

A

LMWH or fondaparinux - short term anticoagulation.
warfarin or NOAC - long term anticoagulation.
compression stockings.
mobilise, stop the pill.

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74
Q

what steps can be taken to prevent DVT?

A

stop the pill.
early mobilisation.
compression stockings/leg elevation.
LMWH/fondaparinux.

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75
Q

how does fondaparinux work as an anticoagulant?

A

factor Xa inhibitor - prevents the final coagulation pathway from continuing, preventing formation of fibrin clot.

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76
Q

how do heparins work as anticoagulants?

A

activate antithrombin, which inactivates thrombin and factor Xa.
LMWHs also act to inhibit factor Xa directly.

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77
Q

how would you stop bleeding in an over-anticoagulated patient?

A

IV vitamin K - warfarin ‘antidote’

protamine = heparin antidote

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78
Q

what is disseminated intravascular coagulation?

A

massive activation of clotting cascade leads to lots of fibrin deposition within vessels.

using up all your platelets and coagulation factors forming these intravascular clots - so get bleeding elsewhere.

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79
Q

give 2 causes of DIC?

A 
sepsis.
major trauma/burns.
advanced cancer.
obstetric complications.
acute promyelocytic leukaemia.
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80
Q

how does DIC present?

A

1) symps/signs of systemic collapse - oliguria, hypotension, tachycardia
2) bleeding - bruising, purpura, haemorrhage, petechiae, oozing, haemturia

  • generalised bleeding from 3 unrelated sites = think DIC
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81
Q

what results would you find on investigation of a patient with DIC?

A

Decrease: platelets, fibrinogen, factor V, factor VIII

increased: prothrombin time (PT), activated partial thromboplastin time (aPTT), D dimer, fibrin degradation products

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82
Q

other than treating the underlying cause, how would you manage a patient with DIC?

A
  • call intensive care
  • maintain blood volume and tissue perfusion - stop bleeding, platelet transfusion, FFP (fresh frozen plasma) and cryoprecipitates (2nd line but no ABO match needed)
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83
Q

what is immune/idiopathic thrombocytopenia purpura (ITP)?

A

isolated thrombocytopenia thought to be due to antiplatelet autoantibodies leading to immune destruction of platelets in spleen.

typically occurs in children w/preceding viral illness or in middle aged women.

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84
Q

what are the main features of ITP?

A

easy bruising/bleeding, petechial rash on skin/mucosa, haemorrhagic bullae in mouth, gum bleeding, menorrhagia.

isolated thrombocytopenia - low platelets, but everything else is normal.

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85
Q

how would you manage ITP?

A

Ix - FBC, blood smear (to rule out other causes), bone marrow biopsy (rule out malignancy)

Rx - if severe active bleeding: immunosuppression with IVIG + prednisolone, + platelet transfusion. works within 1-5/7 and lasts 4/52.

if chronic - rituximab + splenectomy.

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86
Q

what is thrombotic thrombycytopenia purpura (TTP)? pathophysio?

A

MED EMERGENCY - 95% FATAL. consider in any pt w/haemolytic anaemia + thrombocytopenia.

deficiency of protease that breaks down vWF (ADAMTS-13) - widespread platelet adhesion/aggregation leading to microvascular thrombosis + thrombocytopenia. red cells passing these clots rupture due to shear force.

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87
Q

what is thrombocytopenia?

A

low platelets - either decreased production or increased destruction

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88
Q

give some causes of TTP. RFs?

A

congenital
sporadic
autoantibody mediated - pregnancy, SLE, infection

RFs - black, overweight, F, pregnacny

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89
Q

how might a patient with TTP present?

A

pentad of:

  1. fever
  2. renal failure (raised urea/cr)
  3. haemolytic anaemia (pallor, jaundice, pruritus)
  4. thrombocytopenia (purpura, ecchymosis, menorrhagia)
  5. neuro change (coma, focal neuro, seizure, headache, confusion)

+ may get GI symps (N&V&D)
haemolytic anaemia

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90
Q

how would you treat a patient with TTP?

A

urgent plasma exchange + prednisolone (immunosuppression) + antiplatelet agent (aspirin)
DO NOT GIVE PLATELETS.
long term aspirin decreases plt aggregation.

Rituximab targets ab production

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91
Q

what is haemophilia A?

A

X-linked (boys!) recessive inherited factor VIII deficiency.

A&B both tend to present in toddlers. bleeding to muscles and joints.

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92
Q

how would a patient with haemophilia A present?

A

early in life/after surgery or trauma.

bleeds into joints and muscles - arthropathy and haematomas.

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93
Q

how would you diagnose and treat haemophilia A?

A

factor VIII assay

IV recombinant factor VIII. avoid IM injections, aspirin, NSAIDs (bleeding risks).

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94
Q

what is haemophilia B? how is it treated?

A

factor IX deficiency (xmas disease) - same clinical behaviour as haemophilia A.
treat with factor IX.

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95
Q

what is von Willebrand’s disease?

A

deficiency of vWF - leads to platelet dysfunction.
tends to be in teenagers.
AD disease on Ch12. bleeding to mucus membranes and skin.

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96
Q

what clinical signs indicate a platelet disorder (e.g. von Willebrand’s disease)?

A

bruising, epistaxis, menorrhagia, excessive bleeding after tooth extraction

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97
Q

how would you treat von Willebrand’s disease?

A

desmopressin for mild bleeds.

vWF-containing factor VIII concentrate.

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98
Q

what cell lines are affected in acute lymphoblastic leukaemia (ALL)?

A

lymphoblasts - B/T cell precursors. lymphoid cells replace haematopoeitc cells.

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99
Q

which leukaemia most commonly affects children?

A

ALL - acute lymphoblastic leukaemia

rare in adults (75% is under <6yrs old). two spikes again in mid 30s and mid 80s

90% will have complete remission (if <30yo)

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100
Q

name a trigger of ALL

A

ionising radiation during pregnancy

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101
Q

which of the leukaemias is most associated with Downs syndrome?

A

ALL - acute lymphoblastic leukaemia

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102
Q

give some clinical features of acute leukaemias

A

marrow failure - anaemia symptoms, infections e.g. candida (neutropaenia), bleeding/petechial rash (thrombocytopaenia).

circulating cell symptoms - headache, CNS involvement (cranial nerves). Infiltration: skin/gums (some AMLs), hepatosplenomegaly, lymphadenopathy, testicular enlargement.

tumour related symptoms - bone pain, fever, lethargy and fatigue, night sweats, weight loss.

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103
Q

what infections are commonly seen in ALL patients?

A

CMV, measles, candidiasis, Pneumocystis pneumonia (PCP)

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104
Q

what investigations would you carry out on an ALL patient? what would the results show?

A

peripheral blood film and bone marrow aspirate - lymphoblasts, hypercellularity.

CXR/CT scan for lymphadenopathy.
LP for CNS involvement.
pleural tap.

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105
Q

how would you treat ALL?

A

Supportive care:

  • hydration, monitor electrolytes
  • allopurinol (tumour lysis synd)
  • prophylactic anitmicrobials - acyclovir, fluconazole, ciprofloxacin, co-trimoxazole
  • beware neutropenic sepsis

Induction chemo (kill leukaemic cells)

  • prednisolone, vincristine, daunorubicin + tyrosine kinase inhibitor (imatinib)
  • intrathecal methotrexate (for CNS disease)
Consolidate remission (weeks)
Maintain remission (years) - mercaptopurine daily, MTX weekly, vincristine + pred monthly
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106
Q

what cell lines are affected in acute myeloid leukaemia (AML)?

A

blast cells.

clonal expansion of myeloid blasts in bone marrow, peripheral blood or extramedullary tissue. unable to differentiate into neutrophils.

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107
Q

what may trigger AML?

A

long-term chemotherapy

radiation

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108
Q

what is the typical age of onset of AML?

A

around 65

most common adult leukaemia. can be complication of chemo.
5yr survival 25%

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109
Q

how would you diagnose AML?

A

bone marrow biopsy - Auer rods, hypercellularity, blasts >20%. aspirate also used for phenotyping.

peripheral blood film - blasts, Auer rods.

other Ix:
FBC - leucocytosis (incr. WCC) w/ neutropenia, thrombocytopenia, anaemia.
Coag (as baseline) - PT and PTT ?prolonged. normal fibrinogen and D-dimer.
CXR - pulmonary infiltrates.

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110
Q

how would you manage AML?

A

Supportive care:

  • hydrate, watch for electrolytes
  • Allopurinol for acute tumour lysis syndrome (increased urate)
  • leukoreduction - hydroxycarbamide/leukapheresis
  • transfusions of RBC/platelets as needed
  • Rx infections

Induction chemo: daunorubicin and cytarabine.

+/- bone marrow transplant at first remission

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111
Q

what cell lines are affected in chronic myeloid leukaemia (CML)?

A

myeloid - uncontrolled proliferation of myeloid cells in BM.

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112
Q

what are the genetics/pathophysiology behind CML?

A

Philadelphia chromosome - translocation between chromosomes 9 and 22 - t(9;22).

1) Ph chromosome produced BCR-ABLE fusion oncogene
2) produces p210 BCR-ABL protein
3) expressive active tyrosine kinase on surface of myeloid cells
4) unregulated cell division

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113
Q

describe the clinical features of CML

A

1/3 asymptomatic at presentation.

early symps - weight loss, malaise, fever, night sweats, abdo discomfort (due to splenomegaly), arthralgia (increased uric acid from cell turnover)

in 10% the chronic phase will turn into a symptomatic accelerated phase, or blast phase (AML).

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114
Q

which of the leukaemias doesn’t cause recurrent infections?

A

CML - chronic myeloid leukaemia

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115
Q

what investigations would you do in CML? what results would you expect?

A

FBC - leucocytosis, anaemia, thrombocytosis/cytopenia.

bone marrow aspiration - granulocytic hyperplasia.

cytogenetic analysis (FISH) - Ph chromosome.

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116
Q

how would you treat CML?

A

Chemo: IMATINIB - tyrosine kinase inhibitor. SEs = muscle cramps/HF.

+/- allogenic haematopoietic stem cell transplant + high-dose induction chemo.

presence of Ph chromosome = GOOD prognosis.

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117
Q

what cell lines are affected in chronic lymphocytic leukaemia?

A

mature B cells - they have escaped apoptosis.

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118
Q

who does CLL affect? what is the prognosis like?

A

it’s an incurable disease of older people - but some show no/slow progression - have a near normal life expectancy.
(others show active progression so have a worse prognosis).
most common leukaemia.

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119
Q

what can trigger CLL?

A

pneumonia

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120
Q

give some clinical features of CLL

A

anaemia symps.
painless, rubbery lymphadenopathy
B symps:
fever, chills, night sweats weight loss, fatigue

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121
Q

what would a FBC show in CLL? what about other Ix

A 
marked lymphocytosis (raised WCC), especially lymphocytes.
low Hb/platelets.

other Ix:

  • peripheral blood film: smudge and smeal cells
  • flow cytometry: CD5, CD19, CD23 positive
  • CT: hepatosplenomegaly, retroperitoneal/mediastinal lymph nodes
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122
Q

what histological feature differentiates Hodgkin’s lymphoma from NHL?

A

presence of Reed-Sternberg cells ( large multinucleated mirror-image nuclei)

(they look like lil owls)

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123
Q

what are lymphomas?

A

malignancies of lymphoid system - neoplastic transformations of B and T cells which accumulate in lymph nodes –> lymphadenopathy.

lymphomas are SOLID, leukaemias are CIRCULATING.
Dx confirmed by tissue sampling.

124
Q

give 3 risk factors for Hodgkin’s lymphoma

A

affected sibling; EBV; SLE; post-transplant; obesity; Westernization

125
Q

at what ages are the 2 peaks of incidence of Hodgkin’s lymphoma?

A

young adults and the elderly

126
Q

describe the lymphadenopathy seen in Hodgkin’s lymphoma.

A

enlarged, painless, rubbery superficial lymphadenopathy.

most commonly presents with cervical or supraclavicular painless lymphadenopathy “but I do get pain in my neck when I’ve had a drink doctor…”

127
Q

what features of a Hx suggest Hodgkin’s lymphoma?

A
  • Painless supraclavicular or cervical lymphadenopathy (may spontaneously increase/decrease in size)
  • Risk factors
  • B symptoms (25%)
  • Pruritus (10%)
  • Alcohol induced pain
  • Symptoms of mediastinal adenopathy (dry cough, dyspnoea, chest pain, SVC syndrome)
128
Q

what investigations would you carry out in Hodgkin’s lymphoma? what results would you expect?

A 
lymph node biopsy - histology for Reed Sternberg cells.
FBC - low Hb and plt, WCC high or low.
raised ESR = poor prognosis
CXR - mediastinal mass
PET-CT for staging.
PCR - to rule out EBV.
129
Q

how would you manage Hodgkin’s lymphoma?

A

ABVD chemo + radiotherapy - curative for 80%.

Doxorubicin
Bleomycin
Vincristine
Dacarbizine

130
Q

what AIDS defining illness is associated with NHL?

A

Burkitt’s lymphoma - jaw lymphadenopathy

131
Q

how does NHL present?

A

1) Nodal signs - lymphadenopathy (can be rapid)

2) Extranodal signs:
- bone marrow - pancytopenia (fatigue, dyspnoea)
- Splenomegaly (massive in marginal zone) + hepatomegaly
- *Dry cough - mediastinal mass/pneumonia
- Skin (T cell)
- Gut: diarrhoea, vomiting, abdo pain (MALT)
- Bone - bone pain
- CNS

3) B symptoms (less common than Hodgkin’s)
- Night sweats
- Fever
- Weight loss > 10%

132
Q

what investigations would you do in NHL? what would you expect to see?

A
  • FBC - normocytic anaemia, thrombocytopenia or pancytopenia
  • raised ESR/LDH
    • Lymph node core biopsy/bone marrow biopsy - positive (flow cytometry for tumour surface markers + cytogenetics).
  • CT/MRI to stage
133
Q

describe the staging of lymphomas (same is used for NHL and HL)

A

Ann Arbor system (get a number and a letter):
1 - Single lymph node group
2- Multiple on same side diaphragm
3 - Multiple on opposite side diaphragm
4 - Multiple extranodal sites or lymph nodes and extranodal disease

E - extranodal extension
B - weight loss > 10%, fever, drenching night sweats
A - no B symptoms

B symps = worse prognosis

134
Q

how would you manage NHL?

A

R-CHOP-21 - rituximab, cyclophosphamide, hydroxy-daunorubicin, vincristine (oncovin), + 21 days of prednisolone.

(if stage 1/2 might rx with just radiotherapy)
+/- CNS prophylaxis (intrathecal MTX)
+/- growth factor (G-CSF)
+/- antimicrobial prophylaxis (cipro, acyclovir, fluconazole)

135
Q

what cell line is affected by multiple myeloma?

A

plasma cells - malignant clonal expansion - produce excessive amounts of one type of Ig/Ig fragment (monoclonal element) in the serum or urine.

136
Q

what are the diagnostic criteria for myeloma?

A

1) monoclonal protein band on serum/urine electrophoresis
2) increased plasma cells on bone marrow biopsy
3) evidence of end organ damage (hypercalcaemia, renal failure, anaemia)

137
Q

describe the clinical features of myeloma

A

Most commonly presents with:

    • Bone pain (esp back pain!)
    • Anaemia
  • Fatigue
  • Infections
  • Hypercalcaemia
  • Renal impairment

diagnosed by serum and urine protein electrophoresis

138
Q

what investigations would be carried out in myeloma? what would you see?

A

Gold standard = serum/urine electrophoresis. Paraprotein spike. Bence Jones (light chain) proteins in urine.

blood film - Rouleaux formation (RBCs stack on top of each other).

bone marrow aspirate/biopsy - plasma cell infiltrate >10% (minor) or >30% (major)

Skeletal survey - punched out lesions e.g. pepper pot skull; pathological #; osteopenia

raised serum Ca
FBC - anaemia
raised creatinine (renal impairment)
ESR raised due to increased viscosity
139
Q

how would you manage multiple myeloma?

A

Treat complications:

  • bone disease -bisphosphonates + analgesics
  • anaemia - blood transfusion/EPO
  • spinal cord compression - dexamethasone
  • hyperviscosity (reduced cognition/blurred vision) - plasmapheresis
  • AKI - rehydration/ preserve good hydration
  • infection - abx + pneumonia/flu vaccine

Transplant candidate:
- Thalidomide or velcade (bortezomib) based induction + dexamethasone + DVT prophylaxis (aspirin 75mg OD) + autologous/allogeneic stem cell transplant

MGUS - Monitor closely with urine/serum electrophoresis 6 monthly

140
Q

give 3 complications of myeloma

A

hypercalcaemia of malignancy.
spinal cord compression.
hyperviscosity.
acute renal failure.

141
Q

how is malaria transmitted?

A

protozoa that is transmitted by bite of infected female Anopheles mosquito

142
Q

what are the 4 species of plasmodium that cause malaria?

A

P vivax, P ovale, P malariae, P falciparum

143
Q

give 3 general clinical features of malaria

A

fever, malaise, headache, vomiting, diarrhoea, rigors, sweats

144
Q

give 3 features of Vivax/ovale malaria

A

anaemia, tender hepatosplenomegaly, mild illness

145
Q

give 3 features of Malariae malaria

A

relatively mild, more chronic, glomeulonephritis/nephrotic syndrome

146
Q

give 3 features of Falciparum malaria

A

anaemia, jaundice, hepatosplenomegaly, cerebral malaria (fits, confusion, coma), metabolic acidosis, pulmonary oedema, hypoglycaemia, diarrhoea, DIC

147
Q

what investigation would you perform to diagnose malaria? what does this tell you?

A

thick and thin blood smears
thick - diagnoses malaria
thin - quantifies % of infected RBCs, identifies species

148
Q

what must you take into account, before treating a malaria patient?

A

whether they’ve taken any prophylaxis - which type? likely their malaria is resistant, so don’t treat them with this!

149
Q

how would you treat falciparum malaria?

A

uncomplicated - oral riamet or quinine ± doxycycline.

complicated - IV artesunate or quinine.

150
Q

how would you treat non-falciparum malaria?

A

oral chloroquine

151
Q

what drugs can be used as prophylaxis for malaria?

A

mefloquine, atovaquant, proguanil, chloroquine, doxycycline.

152
Q

list 3 causes of macrocytic anaemia

A

B12 deficiency
folate deficiency.
alcohol

153
Q

what must you assess before giving anticoagulation therapy? how would you assess this?

A 
bleeding risk.
HAS-BLED.
Hypertension.
Abnormal liver/renal function.
Stroke.
Bleeding.
Labile INR.
Elderly.
Drugs/alcohol.
154
Q

give a main advantage and disadvantage of NOACs

A

adv - no need for regular INR monitoring - easier for patient.
dis - don’t have an antidote, so patient at risk of massive haemorrhage if injured etc.

155
Q

which leukaemia commonly affects the elderly?

A

CML

156
Q

if you see blast cells on a blood film, what does this suggest?

A

an acute leukaemia

157
Q

if Auer rods are seen on a blood film, which leukaemia is this?

A

AML

158
Q

if smudge cells are seen on a blood film, which leukaemia is this?

A

CLL

159
Q

what are the signs of end-organ damage seen in active/symptomatic myeloma?

A 
CRAB.
Calcium - hypercalcaemia (bones).
Renal failure
Anaemia
Bone disease - lytic or osteopenic lesions e.g. pepperpot skull.
160
Q

give an example of an iron chelator.

how do these drugs work?

A

desferrioxamine.

binds free iron in bloodstream and enhance its elimination in urine.

161
Q

what IS anaemia?

A

a low Hb concentration due to:

1) low red cell mass or
2) increased plasma volume (e.g. in pregnancy)

Leads to:

  • decreased oxygen transport
  • tissue hypoxia
  • compensatory changes (increased RBC production)
162
Q

define severe anaemia and give some physical signs it can cause

A

< 8g/dL (80) - can cause signs of hyperdynamic circulation:

  • tachycardia
  • flow murmur
  • cardiac enlargement
  • increased cardiac output (/can worsen cardiac failure)
163
Q

normal range for mean corpuscular volume?

A

80-100fL
< than this = microcytic
> = macrocytic

164
Q

briefly outline how iron is absorbed/transported/store

A

absorbed in duodenum/jejunum

transported by transferrin
storied in ferritin + haemosiderin

165
Q

what is a sideroblast?

A

an atypical, abnormally nucleated erythroblast with perinuclear iron accumulation

166
Q

what is haemosiderosis?

A

iron deposition at liver, kidney and heart.

this is why you use iron chelation for repeated transfusions etc.

167
Q

what’s the normal structure of haemaglobin for adults/babies?

A

babies have HbF = 2xalpha + 2xgamma.
adults HbA = 2xalpha + 2xbeta.
HbA2 = 2xalpha + 2xdelta - found normally, but is increased in beta thalassaemia.

168
Q

what would you see on investigation for beta thalassaemia?

A
  • FBC = microcytic anaemia
  • peripheral blood smear = microcytic, target cells, nucleated red cells.
  • reticulocyte count = elevated (haemolytic)
  • Hb analysis (electrophoresis):
    major = no HbA, elevated HbF and HbA2
    medium = decreased HbA, elevated HbF and HbA2
    minor = mostly HbA, elevated HbF and HbA2.
  • LFT = elevated total and unconjugated bilirubin (haemolytic)
  • XR skull = “hair on end” sign, widening of diploeic space
  • abdo USS = hepatosplenomegaly
169
Q

give some possible complications of beta thalassaemia

A
  • thrombotic
  • those due to iron overload: arthropathy, pigmentation/bronzing, arrhythmias (leading to CCF), endocrine (ant. pituitary and pancreatic islet cells - slowed growth, delayed puberty, T1DM)
  • transfusion reactions + transmission acquired infections (HIV, HBV, HCV)
  • splenectomy complications
170
Q

what would you see on investigation for alpha thalassaemia?

A
  • FBC - microcytic (low MCV and MCHC)
  • peripheral blood smear - microcytic/hypochromic, target cells, basophilic stippling in 3 gene/HbH
  • elevated reticulocyte %
  • haemoglobin analysis - detects HbH or Hb Bart but won’t detect silent carrier or trait.
  • iron studies - serum iron/ferritin both normal or elevated
171
Q

describe the treatment of alpha thalassaemia

A

1) silent carrier = genetic counselling + education and iron advice (avoid unless deficient)
2) trait = genetic counselling + education and iron advice

3) HbH = genetic counselling + folic acid (1mg, PO) + education. also regular transfusion to >10g/dL + iron monitoring with chelation ± splenectomy ± assess for haematopoeitic stem cell transplant
4) Crisis = Identify cause + monitor + folic acid ± red cell transfusion

172
Q

what is haemolysis and where can it happen?

A

premature destruction of RBC. can happen in two places:

1) intravascular - trauma (e.g. mechanical heart valve), complement mediated lysis
2) reticuloendothelial system/extravascular - macrophages of liver, spleen, or accelerated due to immune targeting by antibodies.

173
Q

what does Coombs’ negative/positive mean?

A

direct antiglobulin test.
used in haemolytic anaemia.
positive = immune mediated
negative = non-immune mediated.

174
Q

what are the two main categories of immune-mediated haemolytic anaemia? how do you treat each?

A

warm = IgG mediated, Rx is steroids

cold = IgM mediated, Rx keep warm.

175
Q

management of G6PD deficiency at acute haemolysis

A
  • maintain fluid intake
  • folic acid 5mg orally
  • blood transfusion if severe anaemia (<7g/dL)
  • renal support if renal impairment
176
Q

what are the characteristics of anaemia of chronic disease? briefly describe the mechanism

A

anaemia + evidence of immune system activation.

release of pro-inflammatory cytokines by infection, neoplasm, autoimmune and trauma. cascade leads to fall in serum iron and decreased RBC survival.

177
Q

what lab results would you expect to see for anaemia of chronic disease?

A
  • normocytic + normochromic / microcytic + hypochromic
  • low reticulocyte count
  • low serum iron
  • low TIBC
  • low transferrin saturation
  • elevated ferritin
178
Q

list some causes of neutropenia

A
  • aplastic anaemia
  • immunosuppression
  • *chemo
  • HIV
  • bone marrow infiltration
  • neoplastic disease
  • infections
179
Q

define neutropenic sepsis - management?

A

T > 38.5 or 2x >38 an hr apart, plus neutrophils <0.5 + hypotension.

Rx - sepsis 6 with tazocin + fluid challenge + G-CSF (SC injection, stimulates neutrophil production)

180
Q

what does the bone marrow do? where are biopsies taken?

A

haemopoiesis - at axial skeleton and long bones (vertebrae, sternum, ribs, skull, limbs)

biopsy is at iliac crest

181
Q

what factors can precipitate a sickle cell crisis?

A 
CHIDS:
Cold
Hypoxia (incl extreme exercise)
Infection
Dehydration
Stress
182
Q

how do you manage an acute sickle cell crisis?

A
  • cross match blood
  • analgesia (paracetamol, ibu, codeine phosphate or morphine IV)
  • supportive care - O2 + treat cause (e.g. correct acidosis)
  • IV fluids ± warmth
  • abx - local guidelines
  • give blood if Hb/reticulocytes fall too quickly
183
Q

what are megaloblasts?

A
  • large structurally abnormal RBCs
    due to defective DNA synth - leads to leukopaenia + thrombocytopaenia.

causes - B12/folate deficiency, drugs (hydroxyurea).
often asymptomatic as such slow onset means body adjusts.

184
Q

what symptoms might help you differentiate between macrocytic anaemia due to folate vs B12 deficiency?

A

B12 you get peripheral neuropathy and neuropsych complaints, folate you don’t.

185
Q

where is folate absorbed? what about B12?

A

folate = proximal jejunum + duodenum. green veg, nuts, liver.

B12 = ileum (combines with intrinsic factor). meat, fish and dairy.

186
Q

list some possible causes of B12 deficiency anaemia

A

1) poor diet - veggie, vegan, old age
2) decreased gastric breakdown - gastric surgery, atrophic gastritis
3) malabsorption - pernicious anaemia, crohn’s, coeliac.
4) drugs - metformin (decreases absorption), PPI/H2 antagonists.

187
Q

briefly explain how B12 is absorbed

A

1) B12 released from food in stomach by peptic acid
2) parietal cells @ gastric fundus produce intrinsic factor (IF)
3) IF binds B12
4) IF-B12 complex travels to terminal ileum
5) endocytosis - complex gets bound to transcobalamin which is then released into blood stream.

188
Q

what neurological symps/signs do you see in B12 deficiency?

A

Paresthesias, ataxia + loss vibration (posterior column degeneration), peripheral neuropathy, dementia, psychosis.
triad of - upgoing plantars, loss of knee jerk, loss of ankle jerk.

not neuro but - LEMON TINGE SKIN (pallor+jaundice)

189
Q

how do you treat pernicious/B12 deficient anaemia?

A

symptomatic + severe = IM hydroxycobalamin 1mg alternate days till no further improvement, then 1mg every 2/12

moderate (no neuro involvement) = IM hydroxycobalamin 1mg 3x/week for 2 weeks, then every 3/12 - lifelong

190
Q

what are the two main types of haematological malignancies?

A

1) bone marrow origin - myeloid disorders

2) lymphatic origin - lymphoid disorder - B or T cell

191
Q

list the main haematological malignancies and define them

A
  • leukaemias: excess of abnormal white cells in peripheral blood (myeloid or lymphoid)
  • lymphomas: tumour presentation w/ local/scattered lumps in lymphatic system
  • myeloproliferative disorders: involve BM, liver + spleen w/ peripheral blood features
192
Q

which haematological malignancies tend to follow an acute course with rapid progression?

A 
myeloid = AML
lymphoid = ALL (T or B cell), high grade lymphoma
193
Q

which haematological malignancies tend to follow a slowly progressive course with years between presentation + clinically relevant condition?

A 
myeloid = CML, myeloproliferative neoplasm (e.g. MDS, PRV)
lymphoid = CLL, low grade lymphoma, myeloma
194
Q

list some conditions/RFs associated with AML

A

myelodysplastic syndrome (MDS)
Downs
bone marrow failure syndromes (e.g. Fanconi, Diamon-Blackfan, aplastic anaemia)
smoking

195
Q

what is tumour lysis syndrome

A

Electrolyte and metabolic disturbance due to breakdown of large number of e.g. leukaemic cells

you get: hyperuricaemia, hyperphosphataemia, hyperkalaemia, hypocalcaemia,renal impairment

196
Q

outline 3 classification systems used in ALL

A

FAB (french/american/british):

  • L1 - small homogenous blasts (children)
  • L2 - large heterogenous blasts (adults)
  • L3 - Burkitt large basophilic B cells with vacuoles

Immunological - uses surface markers
Cytogenetic - chromosomal analysis, Ph chromosome is a poor prognosis.

197
Q

what CNS involvement can you get in ALL?

A

CNS infiltration by leukaemoid cells presents as papilloedema, nuchal rigidity and meningism.

also might get focal neurology CN 3, 4, 6, 7

198
Q

list some potential complications of ALL

A

tumour lysis syndrome
neutropenic sepsis
pancytopenia
chemo SEs

199
Q

outline staging of CLL and how it influences treatment plans

A

Binet:

  • A: <3 nodes + normal Hb and Pt
  • B: >=3 nodes + normal Hb and Pt
  • C: anaemia/thrombocytopenia + any nodes.

Rx:
A+B+asymptomatic = watch and wait, monitor FBC, flow cytometry every 3/12
C = chemo - rtirxuimab + cyclophosphamide + fludarabide +/- stem cell transplant

200
Q

what are two main complications to worry about in CLL?

A

1) hypogammaglobulinaemia - lymphocytes don’t work = no antibodies. pt deficient in IgG/A/M = increased infection risk. may need monthly IVIG
2) autoimmune haemolytic anaemia - dysfunctional antibodies directed towards RBCs. give prednisolone.

201
Q

list some subtypes of NHL?

A

1) Diffuse large B-cell lymphoma (30%) - aggressive/high grade
2) Follicular lymphoma (20%) - indolent/low grade
3) Burkitt’s (HG) (1%) - EBV - characteristic jaw lymphadenopathy (child)
4) Primary CNS lymphoma (1%) - EBV with AIDS

Also:

5) MALT (LG) (gastric mucosa associated lymphoid tissue) - H.pylori
6) Marginal zone - massive splenomegaly
7) T cell

202
Q

what conditions is NHL associated with?

A

autoimmune disorders - Sjogrens, RA, coeliac, SLE

immunodeficiency

203
Q

list some key risk factors for Hodgkin’s lymphoma

A
  • EBV
  • Family Hx
  • Young adult from higher SE class
204
Q

list some causes of Hodgkin’s lymphoma - pathophysiology?

A

Causes:

  • Primary immunodeficiency - ataxia-telangiectasia, Wiscott-Aldrich
  • Secondary immunodeficiency - HIV/transplants
  • Infection - EBV
  • Autoimmune disorders - SLE

Pathophysiology:
Impaired immunosurveillance of EBV infected cells. B cells escape regulation and proliferate

205
Q

what are the 3 main associations of multiple myeloma?

A

1) osteolytic bone disease + hypercalcaemia
2) anaemia (due to accumulation of plasma cells in BM)
3) renal disease

most common haematological malignancy! mean age 60yrs

206
Q

how is multiple myeloma classified?

A

on a spectrum, according to M protein (a monoclonal component) and presence of tissue/organ involvement:

1) MGUS (monoclonal gammopathy of unknown significance) - M-protein <30g/dL, BM clonal cells <10%
2) smouldering (asymptomatic) myeloma - M-protein >30, BM cloncal cells >10% BUT no tissue/organ involvement
3) Active (symptomatic) myeloma - M-protein >30, concal cells >30%, plus CRAB features.

207
Q

what is myelodysplastic syndrome (MDS)?

A

group of malignant haematopoietic disorders characterised by:

1) dysplastic changes in one or more cell lineages
2) ineffective haematopoiesis
3) predilection to develop AML

90% is primary, secondary is due to radio/chemo therapy and has worse prognosis.
usually >70yrs, M, smoker

208
Q

how does myelodysplastic syndrome (MDS) present?

A

1) anaemia - unexplained macrocytic anaemia. usual anaemia symps, worsening angina, CCF.
2) neutropenia - can get granulocyte depletion –> recurrent infections/sepsis
3) thrombocytopenia - bleeding, petechia, bruising, nosebleeds/gums etc

209
Q

how do you diagnose MDS?

A

diagnosis of exclusion:

  • FBC - anaemia (normo/macrocytic), neutropenia, thrombocytopenia, neutrophilia, thrombocytosis.
  • blood film: dimorphic red cells, Pappenheimer bodies, anisocytosis, poikilocytosis.
  • Ferritin + B12 normal
  • BM biopsy - hypercellular with blast cells.
210
Q

how do you manage MDS?

A

supportive blood/plt transfusions + monitoring of iron status - for anaemia/thrombocytopenia.
neutropenia - broad spec abx if sepsis, G-CSF if recurrent infections.

high-intensity chemo!

211
Q

possible complications of MDS?

A
  • Anaemia, thrombocytopenia, low WCC
  • Transfusion related iron overload -> desferrioxamine
  • Transformation to AML
  • Bone marrow failure (leading cause of death)

Median survival - 2 years

212
Q

what is Fanconi anaemia?

A

a mostly autosomal recessive bone marrow failure syndrome.

cells are sensitive to DNA cross-linking.

213
Q

how does Fanconi anaemia present?

A

1) congenital dysmorphic features - triangle face, café au lait + hyperpigmented skin, cardiac and renal malformations, abnormal thumbs
2) pancytopenic BM failure
3) susceptibility to cancer - AML, solid tumours (H&N SCCs, gynae)

presents at <7yrs in similar way to aplastic anaemias, AML, MDS

214
Q

what are platelets?

A

anucleate cells. lifespan 7-10 days. controlled by thrombopoietin (TPO) produced in liver.

bleeding problems can be due to either reduced platelet numbers or reduced platelet function.

215
Q

TTP Ix?

A 
FBC - low plts, Hb <8
reticulocyte count raised
LDH + bilirubin raised
*peripheral blood smear - microangiopathic w/SCHISTOCYTES (RBC fragments)
urea and Cr raised
urinalysis - proteinuria
216
Q

what three things might lead you to worry about DIC?

A 
*DIC is a critically ill pt*
Suspect if:
1) severe sepsis or obstetric or malignancy
2) shock
3) extensive tissue damage -trauma/burns
217
Q

explain how liver disease + vitamin K stuff relates to bleeding problems

A
  • liver is site of coagulation factor and fibrinogen synthesis
  • disease = bleeding + prolonged PT
  • vit K needed to synthesis of 2, 7, 9, 10
  • fat soluble vitamin so deficient in malabsorption esp. obstructive jaundice
  • treat vit K deficiency/liver related bleeding with IV vit K
218
Q

learn coag cascade/platelet physiology if you cba

A

??

219
Q

what drugs influence bleeding?

A

aspirin and clopidogrel = antiplatelets
heparin (factor Xa) and warfarin (factor 2, 7, 9, 10) = affect coag cascade
steroids thin the skin and cause bleeding/bruising

220
Q

what is the mechanism of aspirin?

A

irreversible inhibits COX1

prevents production of thromboxane A2 - TXA2 induces platelet aggregating and vasoconstriction.

221
Q

what is the mechanism of clopidogrel?

A

irreversible P2Y12 antagonist.

P2Y12 is activated by ADP - amplifies platelet activation by activating glycoprotein Gp2b3a.
so clopidogrel inhibits ADP induced platelet aggregation.

222
Q

how does warfarin work?

A

vitamin K antagonist, long half life, orally available but super complicated dosing.
prolongs PT.
prevents synthesis of factors 2, 7, 9 and 10.

monitor with INR (derived from PT):
aim 2-3
some may have higher range 3-4.5

223
Q

give examples of NOACs and mechanisms (might need to check if this is up to date)

A

factor Xa inhibitors = apixaban, rivaroxaban
thrombin (factor IIa) inhibitor = dabigatran.

indicated for DVT/PE and AF.
equivalent to warfarin INR 2-3 but no monitoring.
not easily reversible.

224
Q

list some thrombotic disorders you might screen for if someone presents with DVT. what causes DVTs generally?

A
  • protein C or S deficiency (test = assay)
  • factor V Leiden - AD condition, test with PCR
  • antithrombin deficiency
  • prothrombin gene mutation

BUT 95% are due to hypercoagulable state instead - antiphospholipid synd, cancer, obesity, pregnancy, immobility, nephrotic synd, slow blood flow e.g. sickle cell, PRV etc etc

225
Q

try and learn the ABO system for who can give/receive what blood

A 
O = universal donor
AB = universal receiver
226
Q

what are the group and save/screen and cross match blood tests?

A

group and screen - order if any chance pt needs blood. checks group and Rh status. screens for abs to other antigens.

cross match done for most surgery pts. order if 1 in 10 chance of needing blood - checks the specific blood to be given against pt blood by mixing donor RBCs w/pts serum.

227
Q

list some causes of splenomegaly

A

CHINA - MMM

  • Congestion: portal HTN, portal vein thrombosis, Budd-Chiari, HF
  • Haem: haemolytic anaemia, red cell defects, thalassaemia, sickle cell, leukaemias, PRV
  • Infection: malaria, EBV, CMV, HIV, TB
  • Neoplasm: CML, lymphoma, splenic mets/cysts
  • Autoimmune: RA, sarcoidosis, amyloidosis, SLE, Feltys
  • chronic Myeloid leukaemia
  • Myelofibrosis
  • Malaria
228
Q

list some indications for splenectomy

A

1) Spontaneous rupture at massive splenomegaly (infectious mononucleosis) precipitated by trauma
2) Hypersplenism: ITP, hereditary spherocytosis
3) Neoplasia: lymphoma or leukaemic infiltration
4) Splenic cyst or abscess

229
Q

list some possible complications of splenectomy

A

1) thrombocytosis - platelet count peaks at 7-10/7
2) overhwleming infection - esp. encapsulated bacteria

prophylactic abx + vaccine = oral phenoxymethylpenicillin or macrolides; pneumococcal + flu vaccine.
carry health alert card.

230
Q

give some indications for BM transplant

A

malignant - ALL, AML, CML, HL, MM

non-malignant - thalassaemia, sickle cell anaemia, aplastic anaemia, Fanconi anaemia

231
Q

outline the procedure for a haematopoietic stem cell transplant

A
  • chemo/radiotherapy given before transplant
  • harvest: BM removed from pelvis under GA or peripheral blood stem cells removed from blood via apheresis.
  • given GM IV as inpatient
  • engraftment
232
Q

what’s the difference between autologous and allogenic BM transplants?

A

autologous - stem cells harvested from own BM. pt undergoes ablative/reduced treatment. good as rapid immunity, less infection risk, less risk rejection. BUT not suitable for AML due to high relapse.

allogenic - healthy donor and patient. HLA matching to pt HLA at 3 loci. usually sibling/relative match.

233
Q

list possible complications of a BM transplants

A
  • infection
  • veno-occlusive disease
  • mucositis
  • graft vs host disease (immune response launched by graft against host tissue): occurs at <3/12 - maculopapular rash, N&V, cholestatic jaundice.
  • graft v tumour effect can be beneficial - donor T cells react to diseased lymphocytes of recipient - reduces likelihood of relapse.
234
Q

don’t forget to go through the oncology workbook qus a couple of times

A

see workbook

235
Q

what is the defining characteristic of a malignant tumours?

A

ability to invade and to metastasise to other tissues

236
Q

what are the features of a cancer cell?

A

a cell that undergoes uncontrolled and unregulated cell proliferation with the ability to metastasise to other places in the body

237
Q

what are the “hallmarks of cancer”? - 12 characteristics of cancer cells that underline their behaviour

A
  • evading growth suppressors
  • avoiding immune destruction
  • sustaining proliferative signalling
  • resisting cell death
  • tumour promoting inflammation
  • enabling replicative immortality
  • inducing angiogenesis- genome instability and mutation
  • activating invasion and metastasis
  • deregulating cellular energetics

treatments for cancer should affect these areas!

238
Q

list the stages of the cell cycle in order

A

G0 = resting phase
G1 = pre-DNA synthesis phase (cellular contents, excl. chromosomes, duplicated)
S phase = DNA synthesis (each chromosome is duplicated)
G2 = post DNA synthesis (repair of duplication errors)
M = mitosis

239
Q

at which stage in the cell cycle will cytotoxic chemotherapy be most effective and why?

A

trick qu - depends on how the agent works.
may be cell cycle specific (e.g. MTX) or non-specific (e.g. cisplatin).
more rapidly growing tumour = more cell cycles = more of each cell cycle phase
- so drugs specific for e.g. “S phase” will be most effective against tumours with rapid growth.

240
Q

what’s the difference between pharmacodynamics and pharmacokinetics?

A

pharmacodynamics = effect of the drug on the bodypharmacokinetcs = how the body affects the drug (e.g. absorption, distribution, metabolism, excretion)

241
Q

what three features must be present for a cancer treatment to be effective?

A
  • needs to reach the cancer cells
  • cell must be sensitive to the cytotoxic effects of the drug
  • toxic effect < benefit of drug

key to cancer therapies is finding a drug which specifically kills cancer cells with minimal impact on normal tissue w/appropriate pharmacokinetics - but such a drug doesn’t exist yet!!

242
Q

list the different ways a patient might come to be diagnosed with cancer

A
  • seeking medical advice following symptoms
  • incidental
  • national screening
243
Q

list some of Wilson’s criteria for screening

A

For the condition:

  • recognisable early/latent stage
  • good understanding of the natural course
  • important

For the test:

  • suitable test available
  • acceptable to population
  • should be doing continuous case finding rather than one off

For the treatment:

  • accepted treatment available for disease
  • facilities for diagnosis and treatment available
  • agreed policy for who to treat as patients

Costs:
- cost of case findings (incl diagnosis + treatment) < economic benefit overall

244
Q

define sensitivity

A

ability of test to correctly identify patients with a disease.

= TP / TP+FN

245
Q

define specificity

A

ability of test to correctly identify those without a disease

= TN / TN+FP

246
Q

how do sensitivity/specificity and PPV/NPV relate to prevalence of a disease?

A

sensitivity and specificity are TEST specific - NO relation to prevalence within population.
PPV and NPV will be affected by prevalence within pop.

247
Q

what is the positive predictive value of a screening test?

A

how likely it is that the patient has the disease if they get a positive screening result.

= TP / TP+FP

248
Q

what is the negative predictive value of a screening test?

A

how likely it is that the patient does not have the disease if they get a negative test result.

= TN / TN+FN

249
Q

what is the likelihood ratio for a screening test?

A

how much more likely a patient who tests positive is to have the disease, compared to one who tests negative.

sensitivity / (1-specificity)

250
Q

explain how tumour grading works?

A

a tumour’s grade = extent to which the neoplasm resembles its cell/tissue of origin.
because benign tumours closely resemble parent tissue they don’t get graded.
malignant tumours classified as well, moderately or poorly differentiated.
well = similar to parent tissue, slow growing
poorly = don’t resemble parent tissue, cells are grossly abnormal - rapid growing and aggressive.

251
Q

how does TNM staging work?

A 
T = tumour (grade)
N = nodes (has cancer spread to lymph nodes)
M = metastases

many cancers then converted into Stage 1-4 (carcinoma-in-situ is called Stage 0 is US).
criteria varies but stage IV usually means mets to distinct organs.
used for prognosis - higher stage/grade = poorer prognosis.

252
Q

explain some of the different names for cancer treatment depending on why you’re giving it (can’t think how to rephrase this qu)

A

curative vs palliative intent.
Radical intent = treatment should cure (e.g. radical radiotherapy for prostate Ca, with no adjuvant therapies or surgery)
Neoadjuvant = perioperative
Adjuvant = postop
Palliative intent = to control advance cancer, but with no plan to cure

253
Q

how does cancer recur after curative surgery? what additional therapy can be used to help reduce the chances of this?

A

present of micrometastases.neoadjuvant/adjuvant chemo can help reduce risk of recurrence.
neoadjuvant also used to shrink tumour/reduce the stage to allow simpler operation.
higher TNM staging = increased likelihood of recurrence.

254
Q

briefly outline how radiotherapy works

A
  • administer ionizing radiation to kill cancer/prevent the cells from replicating
  • radiation causes ions to form in cells - free radicals and reactive oxygen species form, which are highly chemically reactive due to free electron
  • that means they react with covalent DNA bonds + other cells
  • if cell is damaged enough = apoptosis, or just DNA damage may = no replication
255
Q

what are the different ways radiotherapy can be delivered?

A

external to body - external beam radiation from linear accelerator is most common type of radiotherapy (high energy X rays penetrate deep into body to try a leave skin unaffected). internal to body (brachytherapy)
systemically (e.g. iodine-131)

256
Q

how does radiation dosing work?

A

dose, no. fractions (sessions) and time for completion depends on the cancer, staging, and palliative vs curative intent.
radiation dose = total amount of irradiation absorbed by each kg of tissue (measured in Grays, Gy).
increasing dosing increases chance of cure.
dose delivered per fraction relates to long-term adverse effects - so for curative intent you give a high dose total over lots of fractions (but palliative you care less about long term effects, so fewer higher dose fractions, but lower total dose as this affects short term adverse effects)

257
Q

give some examples of acute, temporary SEs of radiotherapy

A 
depend on site.
- N&V
- anorexia
- mucositis
- oesophagitis
- diarrhoea
early SEs involve local inflammation, late SEs involve local fibrosis
258
Q

what are the three broad categories of systemic anticancer treatments?

A
  • cytotoxic chemotherapy
  • hormone therapy
  • molecularly targeted therapy
259
Q

what are the main categories of cytotoxic chemotherapies?

A

according to mechanism of action:

  • alkylating agents
  • antimetabolites
  • “natural products” e.g. taxanes, cytotoxic antibiotics
260
Q

how do alkylating agents work? give examples

A

add an alkyl group to guanine base of DNA - formation of crosslinks.
disruption of DNA synthesis, as prevents DNA replication and RNA transcription.
not cell cycle phase specific
e.g. cyclophosphamide, chlorambucil

261
Q

how do antimetabolites work? give examples

A

mostly S phase specific, very little effect during G0 - so most effective against rapidly dividing tumours.
work in a no. ways by inhibition of enzymes or metabolites involved in DNA or RNA synthesis.
e.g. 5-FU, hydroxycarbamide

262
Q

how do natural product chemotherapies work? give examples

A 
these are a no. compounds that all work a bit differently. includes cytotoxic abx, mitotic inhibitors, topoisomerase inhibitors and enzymes.
E.g:
- taxanes - yew tree
- vinca alkaloids - periwinkle plant
- etopside - american mayapple
263
Q

list the different types of problems with chemo that a patient may face

A
  • variable efficacy - secondary to tumour biology/intrinsic resistance.
  • acquired resistance - more you give the drug, the more the cells mutate, until they acquire resistance and then drug is ineffective.
  • toxic SEs on normal tissue - there’s LOADS
264
Q

why does cytotoxic chemotherapy generate so many side effects?

A

it’s a non-specific treatment which targets all cells undergoing cell division.
cells that undergo division more rapidly are more affected than those which do not - this is why you often get GI and skin SEs, as the GI tract and skin cell turnover is so high.

SEs can be divided into general vs specific (to drug). general ones are related to rapidly dividing cells, whereas specific drug SEs may be related to pharmacokinetics.
SE severity IS related to dose strength - this can be a limiting factor in treatment regimens.

265
Q

give some examples of chemo SEs

A
  • nausea ± vomiting
  • taste changes
  • immunosuppression
  • alopecia
  • skin rashes
  • hepatic/renal impairment, heart failure
  • peripheral neuropathy
  • constipation
266
Q

what are the key oncological emergencies to be aware of?

A
  • hypercalcaemia
  • SVC obstruction
  • tumour lysis syndrome
  • neutropenic sepsis
  • spinal cord compression
267
Q

what does “corrected calcium” mean and what’s the value that indicates hypercalcaemia?

A

> 2.6mmol/L
approx 40% circulating calcium is bound to albumin. labs measure total circulating Ca but it’s the unbound, ionised calcium that’s physiologically important.
so Ca levels need correcting to allow for changes in serum albumin.
to correct = add 0.1mmol/L to Ca level for every 4g/L that albumin levels are below 40g/L

268
Q

what are the values for mild/mod/severe hypercalcaemia?

A

mild = 2.6-3.0mmol/L
moderate = 3.01-3.39mmol/L
severe >3.4mmol/

269
Q

list some causes of hypercalcaemia where PTH is high-normal or raised

A

hyperparathyroidism

270
Q

list some causes of hypercalcaemia where PTH is low-normal or low

A
  • MALIGNANCY
  • drugs (thiazides, high dose vit D, lithium)
  • thyrotoxicosis, adrenal insufficienc- sarcoidosis or TB
271
Q

how might hypercalcaemia present?

A

bones, stones, groans and psychic moans!!

  • GI: abdo pain, vomiting, conspitation, anorexia, wt loss
  • GU: polyuria, polydipsia
  • neuro: fatigue, weakness, confusion
  • psych: depression
272
Q

what Ix would you do if suspect hypercalcaemia?

A
  • repeat blood sample for corrected Ca and PTH
  • ECG (shortened QT interval)
  • imaging for bone mets if appropriate
273
Q

outline acute management of hypercalcaemia

A
  • Dx underlying cause
  • correct dehydration w/0.9% saline (rate depends on pt PMH e.g. CCF)
  • after rehydration give IV bisphosphonates via slow infusion
  • treat underlying cause
274
Q

how do IV bisphosphonates work in Rx of hypercalcaemia? give examples and SEs

A
  • inhibit osteoclasts, so reduces bone turnover - will reduce Ca over several days. - eg. pamidronate, zolendronic acid.
  • SEs: flu symptoms, bone pain, myalgia, reduced phosphate levels, N&V, headache, osteonecrosis of jaw
275
Q

how do you manage acute/relapsed hypercalcaemia of malignancy?

A
  • denosumab = human monoclonal antibody that inhibits RANK ligand - so inhibits maturation of osteoclasts.
  • furosemide helps promote renal excretion of Ca - but contentious as can cause dehydration which can worsen hypercalcaemia.
276
Q

briefly outline anatomy of the SVC

A

<p>- provides venous drainage for head, neck, upper limbs/thorax- extends from junction of R and L innominate veins to R atrium- surrounded by: sternum, trachea, R bronchus, aorta, pulmonary artery + perihilar + peritrachael lymph nodes- runs along R side of mediastinumwhen it's obstructed, collateral pathways form to provide alternative route for blood to return to R atrium</p>

277
Q

list possible causes of SVC obstruction

A
  • inside vessel - thrombus, intravascular device
  • inside vessel wall - direct tumour invasion
  • outside vessel - tumours: lung Ca, lymphoma, germ cell tumours, ALL (kids). also “fibrosing mediastinitis”
278
Q

how does SVC obstruction present?

A

big purple swollen face/neck - sudden or gradual onset.
- symptoms: dyspnoea, chest pain at rest, cough, neck+face swelling, arm swelling.
also dizziness, headache, visual disturbance, nasal stuffiness, syncope.

  • signs: dilated veins over arms, neck, ant. chest wall. oedema of upper torso, arms, neck, face. severe resp distress. cyanosis. engorged conjunctiva. convulsions and coma.
279
Q

what Ix might you do for SVC obstruction?

A
  • *can be clinical diagnosis**
  • CXR = widened mediastinum or mass on R side of heart
  • CT scan *
  • doppler studies
  • invasive contrast venography
280
Q

management of SVC obstruction

A
  • elevate head, give O2 - symptomatic relief
  • high dose dexamethasone if acute
  • endovascular stenting - NICE recommended
  • radio/chemo therapy can help.
  • might need to anticoagulate
281
Q

what causes tumour lysis syndrome?

A

abrupt release of large quantities of cellular components into blood following rapid lysis of malignant cells

282
Q

list some risk factors for tumour lysis syndrome

A
  • volume depletion (dehydration/bleeding)
  • renal impairment
  • treatment sensitive tumours (often presents just after starting treatment)
  • high pre-treatment urate, lactate, LDH levels
283
Q

list some causes of tumour lysis syndrome

A

may be spontaneous but usually treatment-mediated, presenting just after initiation of treatment.
most common in haematological malignancies, esp. Burkitt’s lymphoma and ALL

284
Q

how does tumour lysis syndrome present?

A
  • weakness
  • paralytic ileus: constipation, vomiting, abdo pain
  • cardiac arrhythmias: palpitations, chest pain, collapse
  • seizures
  • AKI: reduced UO, lethargy, nausea
285
Q

what Ix might you do for tumour lysis syndrome?

A
  • FBC, U&E
  • serum LDH
  • serum phosphate
  • serum urate
  • calcium profile
286
Q

what metabolic abnormalities would you expect to see in tumour lysis syndrome?

A
  • hyperuricaemia
  • hyperphosphataemia
  • hyperkalaemia
  • hypocalcaemia
  • AKI - raised urea + Cr, reduced UO
287
Q

why do you get renal impairment in tumour lysis syndrome?

A

due to deposition of uric acid and calcium phosphate crystals in renal tubules.
exacerbated by concomitant intravascular depletion.

288
Q

what are the key factors in successful management of tumour lysis syndrome?

A
  • awareness of its causes
  • identifying high risk pts
  • implementing appropriate prophylaxis
  • monitoring of pts during chemo
  • starting active Rx as necessary
289
Q

list some preventative strategies for tumour lysis syndrome

A
  • IV fluids
  • rasburicase (recombinant urate oxidase) - catalyses oxidation of uric acid to allantoin (much more soluble)
  • allopurinol
  • xanthine oxidase inhibitor
290
Q

how do you treat tumour lysis syndrome?

A
  • HYDRATE
  • correct high potassium:
    • 10mls calcium gluconate (10%) IV if K+ >7 and/or ECG changes.
    • IV insulin and dextrose e.g 50mls 50% glucose w/10U rapid acting insulin
    • salbutamol 2.5mg nebs
    • oral calcium resonium 15g/6-8h in water
  • rasburicase + stop allopurinol
  • acetazolamide - alkalinizes urine because uric acid more soluble at pH 7 than 5
  • phosphate binders - to Rx hyperphosphataemia
  • dialysis indicated if severe
291
Q

at what neutrophil count is a pt at risk of neutropenic sepsis?

A

below 1x10(9) /L

292
Q

what cut offs indicate that pts must be treated for neutropenic sepsis?

A

temp ?/=38 or two consecutive readings >/= 37.5C for 2hrs AND absolute neutrophil count < 1x10(9)/L or expected to fall below this

293
Q

how might neutropenic sepsis present?

A
  • any infective symps/signs = headache, D&V, flu-like symps, productive cough
  • asymptomatic yet febrile
  • suspect in any pts presenting w/ new clinical deterioration within 6wks of chemotherapy*
294
Q

what Ix should you do if suspected neutropenic sepsis?

A
  • sepsis 6
  • FBC, U&E, creatinine, LFT, CRP/ESR, coag screen
  • blood cultures/septic screen if unknown source of infection± CXR
  • any clinically relevant swabs/cultures
295
Q

outline initial abx therapy for neutropenic sepsis

A

see WPH guidelines/local protocol.
- offer initial empiriacal abx (TAZOCIN - piperacillin with tazobactam) to all pts with suspected neutropenic sepsis requiring IV therapy, unless CI
- DON’T wait for blood results - give abx within 1hr arriving in hospital.
- check ALLERGY status
at WPH if confirmed neutropenic sepsis, stat does of gentamicin given with tazocin.

296
Q

give some e.g.s of septic complications that may occur following neutropenic sepsis

A

AKI
DIC
multiorgan failure
.should be seen asap by tertiary care to assess risk of these - WPH uses traffic light system

297
Q

how do you manage low risk neutropenic sepsis patients?

A

start on oral abx, observe in hosp for 24hrs before discharge

298
Q

how do you manage high risk neutropenic sepsis patients?

A
  • r/v daily to assess clinical condition, risk of developing complications
  • switch to oral abx after 24-48h of IV treatment if clinically improving + low risk of complications
299
Q

<p>how do you determine when to stop abx in neutropenic sepsis?</p>

A
  • can discontinue if neutrophils normalised, pt asymptomatic and afebrile for 24hr and blood cultures negative
  • if still neutropenic but no complications + afebrile for 5-7/ then can discontinue- in some high risk cases abx will be continued for 10/7, or until normal neutrophil count
300
Q

what drugs might be used in preventing neutropenic sepsis?

A

might be given prophylactic fluoroquinolone
G-CSF in selected cases
if palliative, consider lower dose chemo in subsequent cycles

301
Q

briefly describe relevant anatomy for spinal cord compression, including reflexes

A
  • spinal cord runs from base of skull, terminates L1
  • cauda equina continues below L1 w/ lumbar, sacral and coccygeal spinal nerves
    Reflexes:
  • knee jerk = L3/4
  • ankle jerk = S1
302
Q

list some causes of spinal cord compression

A

MALIGNANCY - secondary by far most common but may be primary.

also:
- trauma
- disc prolapse
- inflammatory disease (RA)
- spinal infection
- epidural/subdural haematoma

303
Q

how may spinal cord compression present?

A
  • radicular pain
  • limb weakness below level of compression
  • difficulty walking
  • sensory level
  • bowel/bladder dysfunction
  • abnormal neurology - LMN signs at level of lesion, UMN signs below level
304
Q

what investigations should be done in suspected spinal cord compression?

A
    • MRI WHOLE spine - not just e.g. thoracic **
  • FBCs, U&Es, LFTs (for liver mets)
  • NICE says no to plain radiographs
305
Q

<p>outline management of spinal cord compression</p>

A
  • analgesia
  • high dose corticosteroids
  • definitive treatment is either surgery or radiotherapy
  • radiotherapy used where surgery not possible, can help with pain control if not definitive
  • surgery allows definitive treatment and spinal column stability
  • chemo used if VERY chemosensitive tumour- hormone deprivation if newly diagnosed prostate Ca causing metastatic spinal cord compression
    also consider
  • bisphosphonate if metastatic bone pain
  • VTE prophylaxis
  • pressure sore prevention
  • bowel/bladder dysfunction - specialist team, ?long term catheter
  • plan for rehab

prognosis = if paraplegia and sphincter involvement at presentation, recovery unlikely

► Med Notes (62 decks)

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