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2a Systems🩺 > Haematology > Flashcards

Haematology 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.

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.

96
Q

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

A

bruising, epistaxis, menorrhagia, excessive bleeding after tooth extraction

97
Q

how would you treat von Willebrand’s disease?

A

desmopressin for mild bleeds.
vWF-containing factor VIII concentrate.

98
Q

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

A

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

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)

100
Q

name a trigger of ALL

A

ionising radiation during pregnancy

101
Q

which of the leukaemias is most associated with Downs syndrome?

A

ALL - acute lymphoblastic leukaemia

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.

103
Q

what infections are commonly seen in ALL patients?

A

CMV, measles, candidiasis, Pneumocystis pneumonia (PCP)

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.

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

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.

107
Q

what may trigger AML?

A

long-term chemotherapy
radiation

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%

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.

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

111
Q

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

A

myeloid - uncontrolled proliferation of myeloid cells in BM.

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

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).

114
Q

which of the leukaemias doesn’t cause recurrent infections?

A

CML - chronic myeloid leukaemia

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.

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.

117
Q

what cell lines are affected in chronic lymphocytic leukaemia?

A

mature B cells - they have escaped apoptosis.

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.

119
Q

what can trigger CLL?

A

pneumonia

120
Q

give some clinical features of CLL

A

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

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

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)

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.

2a Systems🩺 (12 decks)

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