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YEAR 2 > Haematology > Flashcards

Haematology Flashcards

1
Q

Causes of Anaemia with MCV<80

A

TAILS

Thalassaemia
Anaemia of chronic disease
Iron deficiency
Lead poisoning
Sideroblastic

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2
Q

Causes of Anaemia with MCV: 80-100

A

ABCD

Acute blood loss
Bone marrow disorders
Chronic disease
Destruction - haemolysis

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3
Q

Causes of Anaemia with MCV>100

A

RALPH - non megaloblastic

Reticulocytosis - haemolysis
Aplastic anaemia
Liver disease, alcoholism
Pregnancy
Hypothyroidism

B12/Folate deficiency - megaloblastic

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4
Q

What is the predominant haemoglobin in a fetus?

A

Haemoglobin F

2 alpha chains and 2 gamma chains

(gamma chain production dips from 3-6 months old)

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5
Q

What is the predominant haemoglobin in life?

A

Haemoglobin A

2 alpha chains and 2 beta chains

(Small amounts of Haemoglobin A2 -> 2 alpha + 2 delta) chains)

(beta chains reach peak levels from 3-6 months old)

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6
Q

What is the need for different haemoglobin in a fetus than an adult?

A

Foetal haemoglobin has higher oxygen affinity = oxygen flows from maternal to foetal circulation more readily across the placenta

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7
Q

On which chromosomes are alpha and beta chains found?

A

Alpha - chromosome 16 (twice as many alpha genes - life can not be sustained beyond embryonic stage without alpha chains)

Beta - chromosome 11

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8
Q

What are the 3 manifestations of alpha thalassaemia?

A
  1. Thalassaemia trait (carrier - asymptomatic)
  2. Haemoglobin H disease (3/4 genes deleted, excess beta chains form beta4 tetramers = haemoglobin H = high affinity for oxygen + damage RBC membrane = hypoxia)
  3. Thalassaemia- Alpha Major (hydrops fetalis)
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9
Q

What is the inheritance of thalassaemia and sickle cell disease?

A

Autosomal Recessive

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10
Q

What is the consequence of alpha/beta chain precipitants in red blood cells

A

Higher affinity for oxygen = hypoxia

Precipitate in RBC = haemolysis in bone marrow and spleen

– Stimulates extra-medullary erythropoiesis = enlarged bone marrow and spleen = jaundice, deformities of long bones and facial bones

– Damaged RBC + haemoglobin spill into plasma = increased bilirubin, iron - secondary haemochromatosis

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11
Q

What would you find in haemoglobin electrophoresis in B Thalassaemia trait and major?

A

Trait: Decreased HbA, Increased HbA2

Major: Absence HbA, Increased HbA2 + HbF

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12
Q

What would you find in haemoglobin electrophoresis in Alpha Thalassaemia trait and disease?

A

Trait: unable to pick up and decreased of all types so ratio is technically the same.

Disease: Presence of HbH

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13
Q

How does chronic disease cause anaemia?

A
  1. Decreased RBC lifespan - direct cellular destruction via toxins from cancer cells, infections, inflammation
  2. Decreased RBC production- impaired iron metabolism and regulation due to cytokines and ILs.
    - TNF-alpha + IFN-Y = Inhibit EPO production
    - IFN-y = increase expression of DMT on surface of macrophages to allow iron to enter - less available for haemoglobin
    - IL-10 mediates expression of increased ferritin receptors on surface of macrophages
    - IL-6 increases hepcidin
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14
Q

How do distinguish anaemia of chronic disease from iron deficiency anaemia?

A

Chronic disease anaemia
- Starts normocytic but eventually becomes microcytic
- LOW serum iron levels, LOW TIBC, HIGH ferritin
- Presence of chronic disease state - infection, diabetes, autoimmune, malignancy, critical illness, trauma

Iron Deficiency
- LOW serum iron levels, HIGH TIBC, LOW ferritin
- Pica - abnormal craving or appetite for non-food substances - soil, paint, clay
- Restless leg syndrome
- Pencil cells - blood film

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15
Q

4 main causes of iron deficiency anaemia?

A
  1. Inadequate diet
  2. Increased requirements - growth, pregnancy
  3. Malabsorption - GI issues
  4. Blood loss - surgery, GI, menstrual
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16
Q

Typical Findings in Microcytic Anaemia?

A

RBC
- Microcytic
- Hypochromic

  • Target cells - thalassaemia
  • Pencil cells - iron deficiency
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17
Q

Why are RBC more easily damaged and removed early from circulation in hereditary spherocytes?

A

They have an inherited membrane defects - autosomal dominant

Abnormalities in membrane proteins…
1. Spectrin protein
2. Band-3 protein

Intrinsic haemolysis

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18
Q

What is the significance of the G6PD enzyme and if deficient?

A

G6PD reduces NADP+ back into NADPH

Glutathione is oxidised when mops up free radicals
Glutathione reductase uses NADPH -> NADP+ to reduce oxidised glutathione
G6PD reduces NADP+ back to NADPH to repeat process

No G6PD = no NADPH = no glutathione reductase = build up of free radicals = unstable red cell membrane = haemolysis

(Typically asymptomatic until exposed to oxidative stressors)

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19
Q

What cells can be seen on a blood smear in G6PD deficiency?

A

Heinz bodies - free radicals damage haemolgobin molecules = damaged proteins precipitate inside RBC

Bite cells - spleen macrophages try to remove the cells by taking a bite

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20
Q

What is the genetic inheritance of G6PD deficiency?

A

X-linked recessive

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21
Q

What is the mutation in sickle cell?

A

Amino acid substitution from glutamine to valine in beta chains

Valine - more hydrophobic = cause haemoglobin to polymerise

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22
Q

What haemoglobin is present in sickle cell?

A

Haemoglobin S
- 2 alpha chains and 2 mutated beta chains

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23
Q

What is a consequence of Haemoglobin S in sickle cell anaemia?

A

HbS can polymerise when triggered by hypoxia

Become crescent shape - rigid and distorted
Aggregate with other HbS to form polymers that distort red cells = sickling - sickle cell crises

Repeated sickling weakens red cell membrane = premature destruction = intravascular haemolysis

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24
Q

What is a crises in sickle cell?

A

Vaso-occlusion -> Sickle cells get stuck in capillaries - infarct - pain crises

Block spleen = Spleen sequestration
- Howell-Jolly bodies

Lung sickling - life threatening

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25
Q

Causes of non-immune extrinsic haemolytic anaemia?

A

Malaria
Burns
Microangiopathic - TTP, DIC, HUS
Hypersplenism
Mechanical heart valve
Drugs - dapsone, toxin from snake/spider bites, copper

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26
Q

What are typical signs of haemolysis?

A

Jaundice
Dark urine
Gallstones - chronic haemolysis
Signs of anaemia
Splenomegaly

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27
Q

What are classical blood findings of haemolysis?

A

Raised reticulocytes
Raised LDH
Raised bilirubin
Low haptoglobin
Low Hb

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28
Q

What are classical findings on a blood film for haemolytic anaemia?

A

Reticulocytes
Schistocytes - DIC, TTP, HUS
Spherocytes - hereditary spherocytosis
Sickle cells
Howell-jolly bodies - splenic atrophy
Bite cells + Heinz bodies- oxidative haemolysis - G6PD deficiency

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29
Q

What are triggers of oxidative stress in G6PD deficiency?

A

Infections,
Fava beans, soy products
Primaquine, chloroquine, aspirin, NSAIDs, quinidine

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30
Q

What are the 2 important structural proteins in red cell membranes?

A

Band-3 protein and Spectrin

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31
Q

What occurs in warm autoimmune haemolytic anaemia?

A

IgG reacts with RBC at 37 degrees -> Leads to extravascular haemolysis - in liver and spleen

Idiopathic, SLE, RA, CLL

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32
Q

What occurs in cold autoimmune haemolytic anaemia?

A

IgM reacts with RBC below 37 degrees -> leads to intravascular haemolysis, complement activated

Idiopathic, EBV, malignancy

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33
Q

What are the 2 pathophysiologies behind paroxysmal nocturnal haemoglobinuria

A
  1. Somatic mutation in haematopoietic stem cell
    - Mutation in PIG-A gene = GPI protein anchor cannot be synthesised = unable to anchor defence proteins(CD55, CD59) to surface of RBC that normally protect from lysis by complement = MAC-mediated intravascular haemolysis
  2. Background of bone marrow hypoplasia - aplastic anaemia, myelodysplasia
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34
Q

How can you distinguish autoimmune haemolytic anaemias from the other types of haemolytic anaemias?

A

DAT - direct antiglobulin test to identify antibodies

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35
Q

Common triad of symtptoms for aplastic anaemia?

A

Anaemia symptoms - pallor, fatigue
Increased bruising/bleeding
Recurrent infections

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36
Q

How do you get reticulocytosis in haemolysis?

A

Haemolysis stimulates EPO production - erythropoietic hyperplasia = reticulocytosis

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37
Q

What leads to increased absorption of iron?

A

acids, ascorbate, solubilising agents - sugars, amino acids, vitamin C
pregnancy
increased erythropoiesis
haemochromatosis
Increased DMT-1 and ferroportin receptors

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38
Q

What is TIBC?

A

Total/Transferrin Iron-Binding Capacity

Determines the amount of iron that can be bound to unsaturated transferrin - amount of transferrin binding sites per unit

High in iron deficiency (increased transferrin production)
Low in inflammation, iron overload (increased transferrin degradation)

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39
Q

What decreases absorption of iron?

A

Alkalis, phytates, phosphates, tetracyclines
Tea - tanins
Infections - increased hepcidin
High body iron stores

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40
Q

What is the process of iron absorption?

A
  1. Iron reduced from ferric to ferrous form(Fe3+ -> 2+) via vitamin C reductase
  2. Ferrous iron transported into lumen via DMT-1 receptor on lumen membrane
  3. Ferrous iron transported out of enterocyte via ferroportin receptor
  4. Ferrous iron converted to ferric iron via hephaestin
  5. Ferric iron circulates in blood bound to transferrin
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41
Q

What is the role of hepcidin in iron regulation?

A

Hepcidin is an iron regulator made in the liver.

  1. Blocks reuptake of iron into the circulation from the liver.
  2. Blocks ferroportin receptor to prevent iron being released into the circulation from enterocyte
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42
Q

What increases hepcidin production?

A

Infection/inflammation
High iron plasma levels
HFE

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43
Q

What happens to the iron circulating in the blood?

A

75% iron sent to the bone marrow for erythropoeisis

10-20% iron sent to liver and stored as ferritin.

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44
Q

What is the role of HFE gene?

A

HFE regulates hepcidin production - regulates iron absorption

Mutation in HFE = low hepcidin = iron overload = secondary haemochromatosis

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45
Q

How is B12 absorbed?

A

Intrinsic factor made by parietal cell

IF binds to B12 in stomach + travels through intestine

Absorbed in terminal ileum to circulation

B12 travels in blood bound to transcobalamin + IF degraded

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46
Q

Why is B12 required in folate metabolism?

A

B12 required for methylation of Methyl THF to THF

Deficiency in B12 = functional folic acid deficiency - metabolism pathway blocked at methylation point

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47
Q

What occurs in pernicious anaemia?

A

Autoimmune disease

Antibodies against intrinsic factor or against parietal cells.
Impaired absorption of B12 - become deficient = anaemia

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48
Q

What are complications associated with blood transfusions in anaemia?

A

Iron overload risk - organ failure

Tx = Iron chelation therapy - desferrioxamine

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49
Q

What are characteristics on a blood film for B12/Folate deficiency?

A

Hypersegmented polymorphonucleated neutrophils (>5 lobes of nucleus)

Macro-ovalocytes - large, oval RBCs

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50
Q

What can precipitate an aplastic crises?

A

parvovirus infection

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51
Q

What drugs cause folate deficiency?

A

phenytoin
primidone
methotrexate
sulfasalazine

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52
Q

What drugs cause B12 deficiency?

A

colchicine
neomycin
metformin
anticonvulsants
PPI

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53
Q

What drugs cause B12 deficiency?

A

colchicine
neomycin
metformin
anticonvulsants
PPI

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54
Q

How can kidney damage cause anaemia?

A

Reduced production of EPO

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55
Q

What enzymes are inhibited by lead poisoning in haemoglobin production?

A

ALA dehydratase

Ferrochelatase

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56
Q

How can a diagnosis of porphyria be made?

A

Serum levels of enzyme raised

Stool and urinalysis - increased porphyrins

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57
Q

What enzyme inhibition/deficiency is linked to acute intermittent porphyria?

A

PBG deaminase
Accumulation of delta aminolaevulinic acid + porphobillinogen - toxic

Unexplained abdominal pain
Nausea, vomiting, constipation
Neuropschiatric symptoms
Port-wine coloured urine

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58
Q

What enzyme inhibition/deficiency is linked to Porphyria cutanea tarda?

A

Uroporphyrinogen decarboxylase
… Via inherited defect or liver damage(alcohol, oestrogen, HIV, HepC)

Skin manifestation
- blisters and erosions on sun-exposed skin
- hypertrichosis
- hardened yellow skin
- hypermelanosis

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59
Q

What is the first-rate limiting step in Haemoglobin production that can be blocked?

A

Inhibition of ALA Synthase

Blocked by B6 deficiency - pyridoxine, glucose

Leads to sideroblastic anaemia - iron accumulation
Presents similar to haemochromatosis

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60
Q

What is a red blood cell broken up into for metabolism?

A

Globin - amino acids reused for erythropoiesis

Iron - stored or reused

Protoporphyrin - metabolised

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61
Q

What is the metabolism of protoporphyrin?

A

Biliverdin - cleaved haem and iron released

Unconjugated bilirubin - fat soluble, taken to fatty tissues (can accumulate in brain = kernicterus) - circulates in blood bound to albumin

Conjugated bilirubin - water soluble -(conjugated in liver ER by glucoronidation)

Urobilinogen - in urine - blood and kidneys

Stercobilinogen - brown faeces from action of bacteria in gut

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62
Q

Why can liver damage cause anaemia?

A

Portal hypertension
Low hepcidin release - similar to chronic disease
Alcohol toxic to bone marrow

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63
Q

What are 4 mechanisms behind jaundice in bilirubin metabolism?

A

Haemolytic jaundice - increased unconjugated bilirubin in blood (conjugation mechanism overload)

Impaired hepatocytes/liver damage - more unconjugated bilirubin in blood as liver unable to uptake

Impaired bilirubin conjugation - increased unconjugated bilirubin in blood - deficiency in enzymes for glucoronidation in ER

Obstruction - more conjugated bilirubin in blood - normally gallstones or pancreatic carcinoma blocking canaliculi for conjugated bilirubin = pale, chalky faeces, colicky pain

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64
Q

Above what % of blasts are seen in acute leukaemia?

A

20%

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65
Q

What condition can Auer rods be seen?

A

Acute myeloid leukaemia

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66
Q

What are complications of chronic lymphocytic leukaemia?

A

Warm autoimmune haemolytic anaemia

Richter’s Transformation - high grade non-hodgkins lymphoma

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67
Q

What is the pathophysiology behind CML and what is the definitive diagnosis?

A

Philadelphia chromosome - 9:22

Fusion of BCR-ABL - tyrosine kinase constantly activated

FISH - used to detect

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68
Q

In which diagnosis can you see smudge/smear cells on a blood film?

A

CLL

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69
Q

What is small lymphocytic lymphoma?

A

A low grade Non-Hodgkins lymphoma

CLL but when lymphadenopathy with no lymphocytosis

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70
Q

Which group of diseases can transform into AML?

A

Myeloproliferative disorders
- CML
- PV
- ET

Can transform into myelofibrosis – AML

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71
Q

In which lymphoma can Reed-Sternberg Cells be seen on a blood film?

A

Hodgkins Lymphoma

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72
Q

What kind of biopsy should not be used in lymphoma?

A

Fine needle aspirate

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73
Q

What 3 disorders is the JAK2 mutation found?

A

Polycythaemia
Myelofibrosis
Essential thrombocythemia

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74
Q

In which disorder can tear drop cells be seen on a blood film?

A

Myelofibrosis

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75
Q

Which disorder can show hypersegmented neutrophils on a blood film?

A

Megaloblastic anaemia

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76
Q

Which disorder can show schistocytes on a blood film?

A

Intravascular haemolysis

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77
Q

Which disorder can show pencil cells on a blood film?

A

Iron deficiency anaemia

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78
Q

Which disorders can show howell-jolly bodies on a blood film?

A

Hyposplenism
- Sickle cell
- Coeliac disease

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79
Q

What’s the criteria for MGUS?

A

<10% malignant plasma cells in bone marrow
Paraprotein: 10-30g/L
No CRAB symptoms

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80
Q

What is the CRAB criteria in MM?

A

C - hypercalcaemia
R - renal failure
A - anaemia
B - bone lesions

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81
Q

How do myeloma cells impact bones?

A

Myeloma cells produce OPG and RANK-L

Activation of osteoclasts to increase resorption
Inhibition of osteoblasts to reduce production

net result = bone resorption

82
Q

What investigations should be done in MM?

A

Blood film - rouleaux
Bone marrow biopsy >10% plasma cells
Skeletal survey - MRI, CT
Serum protein electrophoresis - paraproteins, IgG, IgA
Serum free light chain immunoassay
Immunophenotyping

83
Q

What is the management in MM?

A

Chemotherapy + Stem cell transplant(if <70)

Fractures - bisphosphonates, prophylactic surgery
Renal failures - dialysis, IV fluids
Hypercalcaemia - IV fluids, radiotherapy
Anaemia - transfusion, EPO
Hyper-viscosity - plasma exchange, chemo
Spinal cord compression - steroids

84
Q

What light chain protein can be found in urine in MM?

A

Bence-Jones Protein - light chain

85
Q

What is Multiple Myeloma?

A

Abnormal proliferation of a single clone of plasma cell.

Immunoglobulin involved normally - IgG or IgA

86
Q

In which disease is a ‘rain drop skull’ seen on an x-ray?

A

Multiple Myeloma

87
Q

What is Waldenstrom’s Macroglobulinaemia and what is the risk of this disease?

A

Monoclonal proliferation of IgM Paraprotein made by lymphoma cells.
Seen as a low grade lymphoma.

Pentameric configuration of IgM = Hyperviscosity Syndrome

88
Q

What is the cause of Renal Failure in MM?

A

Light chain deposition in tubules
Hypercalcaemia
NSAID usage treating pain
Recurrent infections

89
Q

What is a plasmacytoma?

A

Mass of clonal plasma cells
- in bones = solitary plasmacytoma
- in soft tissues = solitary extra-medullary plasmacytoma

90
Q

What are the 2 light chain and how can these be measured in myelomas?

A

Lambda chain
Kappa chain

Testing serum free light chain in myelomas = monoclonal cells will only make 1 type of light chain

91
Q

What is primary amyloidosis?

A

Clonal plasma cells make abnormal light chains (normally lambda) - deposit in organs as insoluble amyloid proteins = organ damage

  • heart - congestive cardiomyopathy
  • kidneys - nephrotic syndrome, renail failure
  • nerves - neuropathy
  • liver - hepatomegaly, liver failure
  • gut - macroglossia, malabsorption
  • skin - deposits
92
Q

What stain is used for amyloidosis on liver tissue?

A

Congo Red Stain

Apple green birefrigence under polarised light

93
Q

What is myelodysplastic syndrome?

A

Abnormal maturation and proliferation of haematopoietic stem cells.

Production of deformed cells = dysplastic = blasts = Reduced survival and improper maturation

Pancytopenia

When >20% blasts in bone marrow = transformed into AML

94
Q

What occurs in myelofibrosis?

A

JAK2 gene mutation = overstimulation of haematopoeisis

Large amounts of megakaryocytes = release fibroblast growth factor = cause fibrosis = scarring of bone marrow = no space of haematopoeisis = pancytopenia

Extra-medullary haematopoiesis in spleen, kidneys, liver for compensation = hepatosplenomegaly

95
Q

Which haematological cancers is down syndrome a risk factor of?

A

Myelodysplastic syndrome
ALL
AML

96
Q

Which leukaemia presents with increased neutrophils and basophils?

A

CML

97
Q

What is the pentad of problems in TTP?

A

Fever
Microangiopathic haemolytic anaemia
Renal impairment
Fluctuating neurological signs - headache, seizures, coma, confusion
Thrombocytopenia

98
Q

What is the aetiology behind TTP?

A

Deficiency of ADAMTS13 = leads to ultra-large vWF multimers = thrombosis in microcirculation

Immune mediated - antibodies against ADAMTS13
Congenital - Inherited autosomal recessive mutation of ADAMTS13

99
Q

What is seen on a blood film and blood count in TTP?

A

Film - Schistocytes + Reticulocytes

Count - Low Hb, Low platelets, Low haptoglobin, Raised LDH
Proteinuria

100
Q

What happens in ITP?

A

The spleen produces IgG autoantibodies against GPIIb/IIIa on platelets
Auto-reactive T cell mediated destruction of platelet and megakaryocyte in the bone marrow

Isolated thrombocytopenia <100

Typically asymptomatic
Can get purpura and gum bleeding and nose bleeding

101
Q

What blood results are indicative of DIC?

A

Low platelets
Prolonged PT and APTT time
Decreased fibrinogen
Elevated D-dimer

102
Q

What is the management of DIC?

A

Platelets
FFP - if PT 1.5x normal
Cryoprecipitate - if fibrinogen < 2
RBC
Fluids

103
Q

What blood group is the universal donor?

A

O group

104
Q

What blood group is the universal recipient?

A

AB group

105
Q

Which 2 patient groups are at increased risk of side effects for future transfusions due to alloantibodies

A

Women with previous pregnancies
Multiply transfused patients

106
Q

When should diuretics be given with red blood cell transfusions?

A

When 2 or more units given
In elderly patients
Patients high risk circulatory overload - heart failure etc

107
Q

What levels of Hb are indications for red blood cell transfusion in certain patients?

A

In a stable patient: <70
In a patient with cardiovascular disease: <80
Patient receiving radiotherapy: must maintain Hb>100

108
Q

What other substance can be given when transfusing red blood cells to avoid a specific side effect?

A

Iron chelation therapy - desforrioxamine

109
Q

Transfusion with which blood product has the highest risk of bacterial contamination?

A

Platelet transfusions

110
Q

What are the platelet count indications for transfusion in different scenarios?

A

No bleeding - platelet count <10
Active bleeding - platelet count<30
Severe bleeding or bleeding at CNS - platelet<100

Prophylactic before surgery - aim platelet count >50
Prophylactic before surgery if high risk bleeding - aim platelet count 50-75
Prophylactic before Surgery at critical site - aim platelet count >100

111
Q

What are the main substances found in cryoprecipitate and what is the main indication to give?

A

High in fibrinogen, factor 8 and 13, vWF

Usually given with FFP
Given when low fibrinogen, with or without bleeding

112
Q

What is the universal donor group for plasma?

A

AB group

113
Q

When is fresh frozen plasma necessary?

A

When PT and APTT ratio >1.5, treating DIC, TTP, massive haemorrhage, liver failure

Contains all clotting factors

114
Q

What are alternative therapies instead of transfusions?

A

Oral or IV iron - if iron deficient anaemia
EPO - stimulate RBC production
IM B12
Tranexamic acid - help stabilise clots and reduce need for platelet transfusions
Cell salvage

115
Q

How much can one unit of RBC increase a patients Hb?

A

By 10g/L

116
Q

How does irradiated red blood cells alter the components?

A

Reduced shelf life from 35 days to 14 days

Reduced red cell membrane stability = Increase in potassium leakage from cells - risk of hyperkalemia not clinically significant unless large volume rapidly transfused or a patient with lower circulating volume, e.g. in neonates

117
Q

How and why does blood need to be irradiated?

A

Done by exposing to gamma or x-ray irradiation - destroys donor lymphocytes - prevents transfusion associated graft vs host disease

Indicated severe T cell immunodeficiency of hodgkins lymphoma, stem cell transplants, certain chemotherapies, patients receiving HLA matched

118
Q

Which patient groups require CMV negative blood products?

A

All neonates - up to 28 days post expected delivery date
Elective transfusions for pregnant women
Intrauterine transfusions

119
Q

What is a group and save and how long can samples be kept for?

A

Blood group and antibody screen tested

Up to 7 days
72 hours if patient pregnant or transfused in previous 3 months

120
Q

What is crossmatching?

A

Mixing patients serum against known donor and suspended in saline to ensure compatibility

If sample agglutinates = cannot use this donor

Can be kept for 72 hours

121
Q

What is an electronic issue?

A

Patient had group and screen on 2 separate occasions
Antibody screens negative + no pregnancy or transfusions in between tests

Donor blood can be issued directly via electronic system - no need to physically cross match donor and recipient blood

122
Q

What is the pathophysiology behind a non-haemolytic febrile reaction and how is it managed?

A

Action of recipients WBCs releasing cytokines and bringing about immune response

Slow or stop transfusion and give paracetamol
Much less common now that RBCs are leukodepleted

123
Q

Who is at risk for TACO?

A

Patients with…

Congestive heart failure
Chronic kidney disease
Severe aortic stenosis
Pulmonary oedema
Neonates

124
Q

What is the main difference between TACO and TRALI in their presentation?

A

TACO will present with HYPERtension, elevated BNP, diuretics have dramatic effect, NO fever

TRALI will present with HYPOtension, fever, normal BNP and pulmonary infiltrates on chest x-ray, pink stained frothy sputum, diuretics have no effect

125
Q

Who is at risk of delayed transfusion reactions?

A

Patients with previous pregnancy or transfusions

Will need more transfusions to manage

126
Q

What is the pathophysiology behind TRALI?

A

2 hit theory

  1. Stressor - primes neutrophils and sequesters them in pulmonary capillaries
  2. Transfusion activates neutrophils - release cytokines - fluid accumulates in lung interstitium = non-cardiogenic pulmonary oedema
127
Q

What occurs in an acute haemolytic transfusion reaction?

A

Due to ABO mismatch - recipients pre-formed antibodies attack donor blood cells leading to intravascular haemolysis

Fever, hypotension, tachycardia, generally unwell
AKI, DIC, flank pain, red/brown urine, jaundice, reduced urine output

128
Q

How is an acute haemolytic transfusion reaction managed?

A

Stop transfusion
Maintain blood pressure and renal perfusion
Fluids, furosemide, corticosteroid, adrenaline

Repeat all checks
Repeat testing of all bloods from donor and recipient - cross match
Perform direct coombs test
Perform tests for DIC - coagulation screen
Examine for bacterial examination - if suggestive start IV abx

129
Q

What are the two lymph ducts?

A

Thoracic duct (begins at cisterna chyli)

Right lymphatic duct

130
Q

How does the lymph fluid reach the heart from the lymph ducts?

A

Lymph ducts drain into the venous angle - between jugular and subclavian vein (good bc low pressure)

Enter superior vena cava to reach right atrium of the heart

131
Q

What is virchow’s node?

A

Left supraclavicular lymph nodes

Can be a sign of abdominal or gastric cancer - due to the draining of the thoracic duct

132
Q

What cells predominant in the cortex, paracortex and medulla of the lymph nodes?

A

Outer cortex - B cells
Inner/paracortex - T cells
Medulla - B cells, plasma cells, macrophages

133
Q

What ensures a one way flow system in the lymphatic vessels?

A

Valves

Movement facilitated by skeletal muscles, smooth muscles of large vessels and thoracic pressure changes pushing on lymphatic vessels

134
Q

Are there more afferent or efferent vessels in a lymph node and why?

A

Many afferent vessels arriving into lymph node
Only one efferent vessel leaving lymph node

To ensure all lymph fluid coming in is forced through lymphatic nodules and germinal centres to illicit immune response if necessary before leaving node

135
Q

What lymph nodes are linked to cervical/ovarian issues?

A

Para-aortic - lumbar lymph nodes

136
Q

What are the 4 steps of haemostasis?

A

Vasoconstriction
Primary haemostasis - platelet aggregation
Secondary haemostasis - coagulation
Fibrinolysis

137
Q

What are the 3 mechanisms behind vasoconstriction in haemostasis?

A

Smooth muscle contraction occurs after injury to reduce blood flow = vasospasm/constriction

  1. Endothelial cells secrete endothelin
  2. Nerve reflex
  3. Myogenic spasm from direct injury
138
Q

What are 3 mechanisms that prevent blood from clotting normally?

A
  1. Endothelial cells secrete prostaglandin and nitric oxide which inactivates platelets + stimulates vasodilation
  2. Heparan sulfate binds to heparin enhancer to activate Anti-thrombin which inactivates factors II, IX, X
  3. Thrombomodulin on endothelial cell binds to Thrombin(II) to activate Protein C which inactivates and degrades factor V and VII
139
Q

How do platelets plug to an injured vessel?

A

vWF bound to collagen exposed in injured vessel.
Collagen binds to platelets via Gp1b = activated platelets

140
Q

How to platelets aggregate to form a platelet plug?

A

Platelets link together via GpIIIb/IIa via fibrinogen

141
Q

What do activated platelets release?

A

ADP = platelet aggregation
Thromboxane - vasoconstriction + platelet aggregation
Serotonin = vasoconstriction

142
Q

What are the factors in the intrinsic pathway of the coagulation cascade and how is it activated?

A

Platelet plug has negative charge surrounding it - this activates factor 12 -> 11 -> 9 -> 8

To then activate factor 10 in common pathway

143
Q

What are the factors in the extrinsic pathway of the coagulation cascade and how is it activated?

A

Tissue factor released in tissue injury activates factor 7

Which then activates (with help of more tissue factor) factor 10 in common pathway

144
Q

What occurs in the common pathway?

A

Factor 10 and 5 activates prothrombin to thrombin(2)

Thrombin converts fibrinogen to fibrin(1)

Fibrin mesh around platelet plug to stabilise clot = bleeding stopped

145
Q

What 2 steps need calcium for help in activation in the coagulation cascade?

A

Activation of factor 10

Factor 10 and 5 for activation of thrombin from prothrombin

146
Q

How does fibrinolysis occur?

A

tPA activates plasminogen into plasmin

Plasmin degrades fibrin mesh

147
Q

What are some fibrin degradation products?

A

D-dimer
Fibrinogen

148
Q

What does PT test and when is it prolonged?

A

Tests secondary haemostasis - the extrinsic and common pathway - factor 7

Prolonged in DIC, Warfarin, Heparin, Liver disease, Vitamin K deficiency

149
Q

What does the aPTT test and when is it prolonged?

A

Tests secondary haemostasis - the intrinsic and common pathway - factor 12, 11, 9, 8

Prolonged in Haemophilia, DIC, vWF Disease, Liver disease, Antiphospholipid syndrome, warfarin, heparin

150
Q

What does the bleeding time test and when is it prolonged?

A

Tests primary haemostasis

Prolonged in thrombocytopenia, DIC, vWF Disease, Aspirin

151
Q

How do the symptoms of primary vs secondary haemostasis disorders present?

A

Primary - prolonged bleeding from initial injury. bleeding from gums, nose, heavy periods, bruising, petechiae

Secondary disorders - bleeding into joints, muscles, tissue, more severe delayed bleeding.

152
Q

What is the inheritance pattern in vWF Disease and how is it treated?

A

Autosomal dominant

Tranexamic acid
Desmopressin - stimulates release of vWF

153
Q

Why does vW disease affect the intrinsic pathway?

A

Factor 8 circulates in the blood bound to vWF

Deficient/defective vWF leads to factor 8 degredation

154
Q

What is the inheritance pattern in haemophilia and what factors are deficient in A and B?

A

X-linked recessive

A - Factor 8
B - Factor 9 - less common

155
Q

What causes thrombocytopenia via increased destruction of platelets

A

Autoimmune - SLE, ITP
Non-immune - DIC, TTP

156
Q

Why can desmopressin be given in Haemophilia A?

A

Desmopressin stimulates release of vWF
vWF can help stabilise factor 8

157
Q

What tests can be abnormal in Haemophilia?

A

Increased aPTT
Decreased serum factor 8/9 assay activity
Genetic mutation testing

158
Q

How does liver disease induce coagulopathy?

A

Inability to produce clotting factors - affect secondary haemostasis
Collects platelets - affect primary haemostasis
Unable to clear toxins in bone marrow - depression of bone marrow function

Treat underlying cause of liver disease to treat coagulopathy

159
Q

What is Factor V Leiden?

A

Autosomal Dominant Disease - leads to functional mutation of factor 5

Unable to be inactivated by protein C

Increased active factor 5 = hyper-coagulable state = VTE risk

160
Q

How does renal disease increase coagulopathy?

A

Depletion/loss of natural anticoagulant proteins - protein c, s, antithrombin

161
Q

What is first line management in TTP?

A

Plasma exchange

  • Removes the large vWF multimers
  • Adds normal ADAMTS13
162
Q

What is the driving force behind DIC?

A

TF activates extrinsic pathway which then activates intrinsic pathway

Inappropriate massive activation of clotting cascade = clots in microvasculature

Eventually depletion of clotting factors and platelets = bleeding

Degradation products from fibrinolysis also blocks clot formation

163
Q

What is the biochemical pattern seen in myeloma - calcium, phosphate, alkaline phosphate

A

High calcium

Normal or high phosphate

Normal alkaline phosphate

164
Q

What can trigger a sudden big drop in Hb and low reticulocyte count in anaemia?

A

Parvovirus - can cause aplastic crises

165
Q

What can typical iron studies look like in a normocytic anaemia of chronic disease?

A

Low serum iron
Low TIBC
Raised Ferritin

166
Q

When do you not give a platelet transfusion even if platelet count<10

A

TTP
HIT
Chronic bone marrow failure
Autoimmune thrombocytopenia

167
Q

What interleukin do myeloma cells express a specific receptor for that acts as a major growth and survival factor?

A

Interleukin 6

168
Q

What is the normal size of a spleen and at what size is it palpable?

A

Normal - 12cm

Palpable - 14cm

169
Q

What are causes of splenomegaly?

A

Malignant - lymphoma, leukaemia, myeloproliferative disorders

Infective - TB, endocarditis, malaria, leishmaniasis

Vascular - portal hypertension - cirrhosis - alcoholism

Haematological - sickle cell, thalassaemia, haemolytic anaemia

Immunological - RA, sarcoidosis, amyloidosis, felty syndrome

Metabolic - gauchers, neumann-pick

170
Q

What are causes of hepatomegaly?

A

Malignant - hepatocellular carcinoma, metastases, lymphoma, leukaemia, myeloproliferative disorders

Haematological - sickle cell

Infective - viral hepatitis, TB, EBV, cysts/abscesses

Congestive - right-sided heart failure, budd chiari syndrome

Inflammatory - alcoholic/autoimmune hepatitis, sarcoidosis

Metabolic - alcoholic liver disease, amyloidosis, haemochromatosis, wilsons

171
Q

What are causes of bone marrow failure?

A

MMMMLLAh

Myeloma
Myelodysplasia
Myelofibrosis
Metastatic cancer
Lymphoma
Leukaemia
Aplastic anaemia - fanconi, DBA, drugs, radiation
Haematinic deficiency

172
Q

How long should the contraceptive pill be ceased before an operation to prevent a PE?

A

4 weeks before the operation

173
Q

What could high uric acid, renal impairment, decreased calcium, raised phosphate and potassium following chemotherapy indicate?

A

Tumour lysis syndrome

174
Q

In DVT investigation - if the D-dimer is positive but ultra sound is negative and you have started an anticoagulant, what should you do next?

A

Stop anticoagulant and repeat ultrasound in 7 days

175
Q

What is the action of Warfarin and what factors does it interrupt the production of?

A

Competitive inhibitor of Vitamin K reductase
(Vit K is required for synthesis of precursor factors into functional clotting factors)

Factor 2, 7, 9, 10, + Protein C and S

176
Q

What is the reversal for warfarin?

A

Stop warfarin
Give vitamin K
Give prothrombin complex if major bleeding and + INR>8

177
Q

Which DOACs inhibit Factor Xa?

A

Apixaban
Edoxaban
Rivoroxaban

178
Q

What drug is a direct thrombin inhibitor?

A

DOAC - dabigatran

179
Q

What is the reversal agent of dabigatran?

A

Idarucizumab

180
Q

What are the durations for anticoagulation in an provoked, unprovoked scenario, active cancer treatment or recurrent clots?

A

Provoked = 3 months
Unprovoked = 6 months
Active cancer treatment = 3-6 months
Recurrent = possibly life long

181
Q

If a patient has Well Score 2+ what is the next step for suspected DVT?

A

Do a doppler ultrasound

Start anticoagulant if US can not be done within 4 hours

Do d-dimer if US negative

182
Q

What is the next step if wells score <1 for suspected DVT?

A

D-dimer test within 4 hours

if raised - then do a doppler ultrasound

183
Q

What is the mechanism of action of unfractionated heparin?

A

Activates antithrombin III = inactivates factor IIa, Xa

184
Q

How is unfractionated heparin monitored and what is the reversal agent?

A

Monitored using APTT ratio - every 6 hours until patient stable

Reversal agent = protamine

185
Q

What is the mechanism of action of LMWH?

A

Mainly inhibits factor Xa
Indirectly through combining with antithrombin

186
Q

Which drug can cause neutrophilia?

A

Prednisolone

187
Q

What is the mode of action of tranexamic acid?

A

(Synthetic derivative of lysine)

Reversibly binds to lysine receptor sites of plasminogen or plasmin

Prevents plasmin from binding to and degrading fibrin

188
Q

What is the threshold of haemoglobin levels for a transfusion with red blood cells?

A

70g/L without ACS
80g/L with ACS

189
Q

Deficiency in what increases the risk of which blood transfusion reaction?

A

IgA deficiency increases the risk of anaphylactic blood transfusion reactions

190
Q

Which antibodies are predominantly involved in acute haemolytic transfusion reactions?

A

IgM antibodies cause red blood cell destruction

191
Q

Which anaemia causes an increase in red blood cells?

A

Thalassaemia
because need more red blood cells as they are small and have less Hb

192
Q

What is the translocation in APML?

A

15 and 17
Fusion of PML and RAR- alpha genes

Associated with DIC

193
Q

What is the translocation in Burkitt’s Lymphoma?

A

8 and 14

194
Q

What is the translocation in follicular lymphoma?

A

14 and 18

195
Q

What is the translocation in mantle cell lymphoma?

A

11 and 14

196
Q

What are the electrolyte changes in tumour lysis syndrome?

A

HIGH - potassium, uric acid, phosphate

LOW - calcium

197
Q

What are symptoms of tumour lysis syndrome?

A

Abdominal pain
Weakness
Nausea and vomiting
Diarrhoea
Dysuria/oliguria

198
Q

What are complications of tumour lysis syndrome?

A

AKI
Cardiac arrhythmias
Seizures
Death

199
Q

What is the prophylaxis and treatment that can be used in tumour lysis syndrome?

A

Prophylaxis high risk:
- IV allopurinol or IV rasburicase
- Fluid hydration
TX: rasburicase + IV fluids + electrolyte imbalance correction

Prophylaxis low risk:
- Oral allopurinol
- Fluid hydration
TX: allopurinol + IV fluids + electrolyte imbalance correction

200
Q

What is the triad of symptoms for Hemolytic-uremic syndrome and what commonly causes it?

A
  1. Microangiopathic haemolytic anaemia
  2. Thrombocytopenia
  3. Acute Kidney Injury

Commonly caused by strains of E.coli -> release shiga-like toxin that damages lining of blood vessels

Nonimmunologic platelet destruction. Endothelial damage is common. Loose strands of platelets and fibrin are deposited in multiple small vessels and damage passing platelets and red blood cells (RBCs), causing significant thrombocytopenia and anemia (microangiopathic hemolytic anemia). Platelets are also consumed within multiple small thrombi, contributing to the thrombocytopenia.

201
Q

What is hereditary haemorrhagic telangiectasia?

A

Autosomal dominant condition of abnormal blood vessel formations which causes bleeding

  • Telangiectasia and AVM formations
202
Q

What is the immune mechanism behind heparin-induced thrombocytopenia

A

Heparin binds to protein on inactivated platelets to form complex ⇒ Heparin-PF4
- The Heparin PF4 complex can be immunogenic in certain people
- Recognised by circulating IgG antibodies in the blood
- IgG bind mark the H-PF4 complex for destruction within the spleen
- Antibody binding to platelet activates it → release procoagulant chemicals which triggers platelet aggregation
- Form clots within the body

YEAR 2 (8 decks)

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