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PHASE 2A MEDICINE - ANJALI createdd > Haematology (inc oncology) > Flashcards

Haematology (inc oncology) Flashcards

1
Q

What is the process of red blood cell formation?

A

Erythropoeisis:

  • Haematopoietic stem cells –>Myeloid progenitor cell–> Erythrocyte
  • Hemocytoblast –>Proerythroblast (committed) Developmental pathway:Early erythroblast – ribosome synthesis–>Late erythroblast – Hb accumulation –>normoblast–> Ejection of nucleus–> reticulocyte–>mature Erythrocyte released into blood stream
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2
Q

Do mature erythrocytes produce globin?

A

No – hence the globin chains need to be stable so they can survive for 120 days

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3
Q

What are the characteristics of the mature erythrocyte?

A

Ability to bind oxygen + be compressed an squeezed into narrow capillaries:

  • Lost its nucleus
  • Full of Hb
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4
Q

Key driver of erythropoiesis

A

Erythropoietin - EPO

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5
Q

Where is EPO produced?

A

Mainly kidney

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6
Q

When does EPO production increase?

A

When RBC count lowers

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7
Q

All the controls of erythropoiesis?

A
  • Hormones: EPO, Testosterone, thyroid

- Nutrients: Iron, folate, B12

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8
Q

How much can the marrow increase its Red cell production?

A

Up to 8x the normal rate . If red cell loss/ destruction continues after this point –> anaemia

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9
Q

Structure of Hb?

A

Tetramer protein:

  • 4 linked globin chains – 2 pairs
  • Central haem molecule – with iron at its centre (4 per molecule of Hb)
  • Gives blood the red colour
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10
Q

What is the normal level of Hb?

A
  • Women: 12-16g/dL – g/L in hospitals so 120-160

* Men: 13.5-17.5g/dL

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11
Q

What are the different types of Hb?

A
  • Adult
  • Fetal (portland and gower)
  • Embryonic (HbF)
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12
Q

What is embryonic Hb?

A

Hb Portland and Hb Gower

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13
Q

When does fetal Hb replace embryonic Hb?

A

By 5 weeks gestation

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14
Q

What is embryonic Hb?

A

HbF: 2 alpha and 2 gamma chains – 85% of total Hb

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15
Q

After birth what happens?

A

HbF production starts to decline and HbA – adult Hb starts taking over

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16
Q

What is adult Hb?

A

HbA- majority 97%, small amount of HbA2 and even tinier amount of HbF.

  • 2 alpha globin chains
  • 2 beta globin chains
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17
Q

what is the inheritance of Hb?

A
  • Chr 16: 2 genes on each chromosome that code for alpha chains – alpha globin –>4 genes in total (2 from each parent)
  • Chr 11: 1 gene on each chromosome that code for beta globin chains –>2 genes in total (1 from each parent)
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18
Q

2 broad types of Hb disorders?

A

o Thalassemia: Quantiative defect , structurally normal globin chain
o Sickle cell disease: Qualiative defect – abnormal Hb chains

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19
Q

What are thalassaemias?

A

Due to low/absent production of a particular chain of Hb – either alpha or beta. Phenotypically vary greatly. Cause Anaemia

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20
Q

Why do thalassaemias cause anaemia?

A

Multifactorial:
o Insufficient globin chains –> excess of one type–>causes precipitation of dominant chain within the cell –>whole cell is less structurally stable (bc globin chains like to be paired – an alpha chain will preferentially pair with a beta chain etc)
o Causes abnormalities in the red cells
o These reds cells are then destroyed (apoptose in the bone marrow / if escape into the circulation –>prone to be lysed –>chronic haemolytic anaemia)
o Additional ineffective erythropoiesis

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21
Q

Thalassaemias cause what type of anaemia?

A

Chronic haemolytic anaemia

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22
Q

What are the types of thalassaemia’s?

A
  • Alpha Thalassaemia – deletion of one or more of the genes coding for alpha chains
  • Beta thalassaemia – mutation within the genes encoding the beta chains
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23
Q

Why is alpha thalassemia a phenotypically heterogenous condition?

A
  • 4 genes control its production – 2 inherited from each parent on Chr 16
  • Most people with it only inherit 1 or 2 affected/ deleted genes –> produces a very mild disease
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24
Q

What does the offsprings phenotype depend on?

A
  • Number of deleted genes inherited

* Location of deletion ( both deletations on one chromosome/ on 2 different chromosomes)

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25
Q

What are the alpha thalassaemia phenotypes and genotypes?

A
  • Normal alpha genes on Chr 16
  • a+ thalassaemia trait: one deletion on one chromosome - normal /minimal change
  • a+ thalassameia homozygote - MCH<25pg
  • Hb H disease: 3 deleted genes: moderate severe
  • Hydrops Fetalis: all deleted, fatal
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26
Q

If both deletions are on the same chromosome what is it termed (thalassemia)?

A

Alpha 0

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27
Q

If a deletion is on each chromosome what is it termed (thalassaemia)?

A

Alpha +

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28
Q

Phenotype of alpha+ trait?

A

normal/minimal changes to Hb, MCV and MCH

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29
Q

Does alpha 0 or alpha + show a worse phenotype?

A

Both alpha 0 and alpha + are phenotypically indistinguishable –>both will have more marked changes. Mean cell Hb <25pg

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30
Q

What happens if an alpha 0 carrier has a child with an alpha+ carrier?

A

Potential for offspring to have a clinically significant disease:

  • Hb H disease or
  • Hydrops Foetalis
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31
Q

What are the clinically signidicant alpha thalassemia diseases?

A
  • Hb H disease or

- Hydrops Foetalis

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32
Q

What is Hb H disease?

A

alpha thalassemia
• Results from inherited 3 deleted genes
• Causes moderate  severe anaemia: Hb 30-100g/L, MCH 15-120pg

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33
Q

What is Hydrops Fetalis?

A

alpha thalassemia
• Fatal syndrome in babies: once they’re embryonic Hb disappears –> become more and more severely anaemic–> ascites and oedema
• Predominant Hb becomes Hb barts- tetramer of gamma globin chains – can bind oxygen but wont release it
• Most babies will die in utero or shortly after birth

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34
Q

What can be done to improve survival in Hydrops Foetalis?

A

In utero transfusions

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35
Q
  1. How would you diagnose alpha thalassemia?
A
  • Typically blood film features – small, pale, microcytic, hyperchromic red cells
  • PCR is the only diagnostic test (Hb electrophoresis will show variant Hbs but not diagnose it). PCR is not always required
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36
Q
  1. What is the Treatment for alpha thalassemia?
A

o Alpha thalassemia trait: no treatment – often just incidental finding on blood test – microcytosis/ mild microcytic anaemia
o HbH disease: Folic acid supplementation, particularly when pregnant. Prompt treatment of infection. May require transfusions

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37
Q

Why is folic acid given for HbH disease Tx?

A

Folic acid depletes rapidly when haemolysing + folate deficiency will worsen their anaemia

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38
Q

What is the carriage of alpha thal like?

A

Very common carriage worldwide

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39
Q

What is the prevalence of severe alpha thal disease?

A

Rare – bc of distribution of a0 thal. Significant a thal disease (HbH or Barts hydrops) confined to Eastern Med and Far East

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40
Q

During antenatal screening for alpha thal, what is important to consider?

A

Individuals from high risk areas will require partner testing

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41
Q

What is the phenotype of beta thalassaemia like?

A

Wide heterogeneity:

  • Severity not always associated with genotype.
  • Hundreds of diff mutations which all cause reduction of beta globin production to a different degree
  • Phenotype affected by other factors – coinheritance of other Hb disorders (alpha thal, sickle cell)
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42
Q

What are the distinct entities of beta thalassaemia?

A

o Thalassaemia carrier / heterozygote - asymptomatic

Inheritence of 2 copies:
o Thalassaemia Intermedia – less severe anaemia and can survive without regular blood transfusions
o Thalassaemia Major – Transfusion dependant

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43
Q

What is the B thal trait?

A

Carrier state – inherit one copy of faulty Hb beta gene.
Usually asymptomatic + Hb> 10g/dL
- Microcytic – rbc smaller than normal
- Abnormal blood film – red cells look like targets
- Usually abnormal Hb electrophoresis (also useful to exclude co-inheritance of Hb variant) – Hb A2 will be slightly higher in b thal carriers

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44
Q

In people with B thal trait, what is it important to check?

A

Iron levels – should be normal (as the other characteristics can be confused with Iron deficiency anaemia) Exclused iron deficiency as the cause of the microcytosis

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45
Q

Tx of b thal trait?

A

No usually required. B thal trait usually picked up incidentally

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46
Q

What is B thal intermedia

A

More anaemic than carrier state but not requiring transfusion

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47
Q

Inheritance of B thal intermedia?

A

Several diff mechanisms:

  • Inheritance of 2 mild allelels
  • Inheritance of 1 severe allele
  • Co-inheritance of alpha thal –> makes homozygous beta thal milder
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48
Q

Clinical presentation of B thal intermedia?

A
  • Hepatosplenomegaly: common feature
  • High Hb and very few symptoms – in some people
  • Low Hb and skeletal deformaties + impaired growth – in some people
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49
Q

When does B thal major present?

A

Childhood, usually 6-12months

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50
Q

Clinical presentation of B thal major?

A

Severe symptoms:

  • Anaemia + failure to thrive
  • Failure to feed
  • Listless
  • Crying
  • Pale
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51
Q

Severity of anaemia in B thal major?

A

Moderate to severe. Hb 30-70g/l

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52
Q

Blood signs in B thal major?

A
  • Hb 30-70g/L, MCV and MCH very low
  • Abnormal blood film: large and small (irregular) very pale red cells, NRBC
  • Hb F>90% on Hb electrophoresis. Normally you would only see this in a neonatal blood sample
  • Normal ferritin
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53
Q

Why are there complications in B thal major (pathophysiology)?

A

As Erythropoeisis is ineffective –> unchecked feedback of severe anaemia–> attempted increased erythropoiesis –>soon expands out of the bone marrow – extra medullary haematopoeisis (liver and spleen)

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54
Q

Complications of untreated B thal major?

A
  • Skeletal abnormalities: bone marrow expansion also erodes through bony cortex . typical facial bone changes
  • Multi-organ issues: hepatosplenomegaly, wasting
  • Secondary haemochromatosis: ineffective erythropoiesis interrupts normal Iron metabolism diabetes, delayed puberty, affects fertility
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55
Q

Tx of B thal major?

A
  • Blood transfusions: Every 2-4 weeks
  • Endocrine hormone replacements
  • Tx and prevention of osteoporosis
  • Prompt tx of infections – bc theyre at higher risk of serious bac infections

newer Tx:

  • Allogenic bone marrow transport: rare but successful
  • Gene editing therapies being developed
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56
Q

Aim of transfusion in B thal major?

A

Maintain a pre-transusion Hb between 95 and 100g/L –>should suppress ineffective erythropoiesis–> avoid hepatosplenomegaly and skeletal abnormalities. Children should grow and develop normally

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57
Q

What are the risks of Blood transfusion?

A

Risk of huge toxicity of excess iron burden. Patients regularly monitored for signs of Iron dysfunction. Sites most sensitive to iron loading regularly monitored – by cardiac MRI, hormone and diabetes screening, Liver MRI

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58
Q

What is the sickled haemoglobin – HbS?

A

Variant of the beta Hb chain

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59
Q

Inheritance of sickled cellHb (HbS)?

A

Autosomal recessive

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60
Q

What does sickle cell disease refer to?

A
  • The homozygous state – (SS)
  • Combined heterozygotes (SC or SD - Thalassaemia) – if the other beta globin is also abnormal in some way (another Hb variant or beta thalassaemia)
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61
Q

Where is carriage and the disease distributed worldwide?

A

Predominantly in areas where malaria is endemic. 15,000 SS in UK

62
Q

What do sickle cell carriers have?

A

1 abnormal beta globin gene but will still produce normal beta globin chains (as the condition is autosomal recessive)

63
Q

What advantage do HbS carriers have?

A

Carriage offers protection against falciparum malaria

64
Q

What is the genetic abnormality in the beta globin gene (in HbS)?

A

Single amino acid substitution: missesense Glu –> Val

65
Q

Describe the pathophysiology of sickle cell disease?

A
  • Red cells containing HbS deform in low oxygen conditions bc the Hb easily polymerises –> deforming the rbc’s–> form characteristic ‘sickle shape’
  • Sickled cells don’t pass through blood vessels easily – sticky and lodge themselves on vascular endothelium –>vascular occlusions: acute and longer term crisis
  • Chronic haemolysis: depletes NO- needed for healthy vascular endothelium–> pulmonary hypertension + skin ulceration
66
Q

Phenotype of sickle cell disease?

A

Highly variable: Few –>severe symptoms

67
Q

Characteristics of sickle cell disease?

A
  • Chronic hameolytic anaemia
  • Vascular problems: occlusions, hypertension, skin ulceration
  • Spleen infacrtion in childhood–> asplenism + increased risk of infections
68
Q

Why does the spleen usually infarct in childhood in sickle cell disease?

A

Repeated crisis

69
Q

Characteristics of anaemia in sickle cell disease?

A

Chronic haemolytic anaemia:
• Usually 60g/dL-90g/dL
• High reticulocyte count – goes up further in acute haemolytic crisis
• No HbA on Hb electrophoresis (90%HbS with variable HbF)
• Anaemia usually well tolerated

70
Q

Why is the anaemia in sickle cell disease usually well tolerated?

A

HbS has a reduced oxygen affinity ie: it gives up oxygen more easily

71
Q

What is the association with HbF and sickle cell disease?

A

HbF is protective – those with a higher F percentage (e.g if they have hereditatory persistence of fetal Hb) –>likely to have less severe symptoms

72
Q
  1. What are the acute complications of sickle cell disease?
A

o Painful crises: dactylitis in children. Can be triggered by temp changes, infection, dehydration
o Sequestration crises: spleen (common) and liver
o Infections: Hyposplenism
o Chest complications: Acute chest syndrome
o Abdominal: gallstones, cholangitis
o CNS: acute strokes

73
Q
  1. When does sequestration occur (sickle cell disease)?
A

Generally in childhood (can occur in pregnancy).

74
Q

What does sequestration in the spleen cause?

A

splenic infarction

75
Q

Patients with sickle cell disease are prone to what infections?

A
  • Pneumococcal
  • Neisseria meningitidis
  • E.coli
76
Q

Why is there manifestations of acute chest syndrome in sickle cell disease (pathophysiology)?

A

Sickling in the pulmonary vasculature. Can be fatal if not treated daily

77
Q

Why are gallstones common in sickle cell disease>

A

Chronic haemolysis and release of bilirubin–>accumulates as bile pigment stains

78
Q
  1. What are the consequences of gallstones?
A

Pain + can lead to infection of the biliary tract

79
Q
  1. What are the chronic complications of sickle cell disease?
A

o CNS: silent infarcts  cognitive deterioration over time
o Eyes: Proliferative retinopathy, retinal detachments
o Bones/Joints: Avascular necrosis and chronic pain. Arthritis
o Kidneys/Genituorinary:
- Sickle nephropathy
- Chronic renal impairement contributed by hypertension, drugs, recurrent renal crisis
- Reccurent priapism can lead to erectile dysfunction if not managed early

80
Q

Acute management of sickle cell disease?

A
  • Pain control. Multimodal anaelgesia. Opiods first line Tx in severe pain (opposite to traditional anaelgesic ladder)
  • Fluid hydration – if needed
  • Supplemenatary oxygen – if needed
81
Q
  1. What is the acute management of patients (HbS) with severe uncontrolled pain crisis/ strokes / chest syndrome?
A

Exchange transfusion – patients red cells are venessected away + cross matched blood is used to replace the volume

82
Q
  1. How are chronic complications managed (HbS)?
A

Regular follow up , monitoring and modifying of any potential risk factors e.g BP , blood glucose

83
Q

what is the disease modifying Tx in Sickle cell disease?

A

o Regular exchange transfusion
o Hydroxycarbamide – increasing HbF percentage

o Allogenic bone marrow transplant – use is limited
o New hope – gene therapy

84
Q
  1. What are the 2 important membranopathies?
A

o Hereditary Spherocytosis

o Hereditary eliptocytosis

85
Q

Most common membranopathy?

A

Hereditory Spherocytosis

86
Q

Inheritance of heriditory spherocytosis?

A

o Autosomal dominant mutations mostly (75%), Recessive forms – have a more severe phenotype

87
Q

Pathophysiology of hereditory spherocytosis?

A

structural protein losses –> unstable RBC membrane – not bioconcave , they are spheres- smaller surface area for oxygen diffusion + RBCs don’t survive for as long

88
Q

How is diagnosis of heridatory spherocytosis made?

A
  • Blood film
  • Biochemical markers of haemolysis
  • Family History
  • Clinical findings
  • If doubts – further tests can be done inc osmotic fragility test
89
Q

Where is heridatory spherocytosis most common?

A

Northern European origin

90
Q

what are the clinical features of hereditaroy spherocytosis?

A

o Mild : compensated haemolysis (Hb 110-150), raised reticulocytes
o Mod-severe: Hb 80-110 60%, splenomegaly becomes detectable during childhood, gallstones common

91
Q

What is the treatment for hereditary spherocytosis?

A

Supportive care with folic acid replacement

  • Splenectomy if severe
  • Vaccination
92
Q

How do red cells produce energy?

A

Glycolysis – anaerobic

93
Q

Key enzymes needed for glycolysis?

A
  • Glucose-6-phosphate dehydrogenase (G6PD)

- Pyruvate kinase

94
Q

What are 2 enzymeopathies?

A
  • G6PD deficiency

- Pyruvate Kinase deficiency

95
Q

What is the most common enzymopathy?

A

G6PD deficiency

96
Q

What is the cause of G6PD deficiency??

A

Wide variety of mutations in the G6PD gene

97
Q

What is the inheritance of G6PD deficiency?

A

X linked – predominantly affects men but women may also be

98
Q

Pathophysiology of G6PD deficiency?

A

Catalyses the reduction of NADP  NADPH in the pentose phosphate pathway. NAPDH protects the cell membrane and Hb from oxidative damage – in erythrocytes its only produced via this pathway. G6PD deficiency makes them prone to cell lysis

99
Q

Prevalance and global distribution of G6PD deficiency?

A

Middle east, SE asia, southern Europe and West Africa

100
Q

How is G6PD deficiency diagnosed?

A

Screening test for NADPH

101
Q

Clinical features of G6PD deficiency?

A
  • Haemolysis after exposure to oxidants and infections
  • Most asymptomatic
  • Crisis characterised by haemolysis, jaundice and anaemia
  • Picked up in neonate as neonatal jaundice
102
Q

Why is there haemolysis in G6PD deficiency?

A

Abnormal rbc’s caught and picked up by the spleen

103
Q

What else can G6PD deficinecy be precipiated by?

A

o Broad beans –> Favism (people experience haemolysis after eating broad beans)
o Drugs
o Infection

104
Q

What drugs can cause drug induced haemolysis?

A
  • Primaquine
  • Sulphonamides
  • Nitrofurantoin
  • Quinolones
  • Dapsone
105
Q

WHat is the presentation of drug induced haemolysis?

A

Usually occurs 1-3 days after drug is administered. Anaemia is at its most severe 7-10 days after the drug.
- Crisis: jaundice, dark urine, haemolysis, anaemia –> usually self limiting

106
Q

What is the presentation of favism?

A

Can occur within hours of injesting broad beans, can be much more severe–> crisis. Investigations will show spherocytes and fragments on the blood film. Unconjugated bilirubin will be high + reticulocyte count will be high

107
Q

Management of favism?

A

Avoid broad beans / drugs , transfusion if anaemia is severe

108
Q

Inheritance of pyruvate kinase deficinecy?

A

Autosommal recessive

109
Q

Pathophysiology of Pyruvate Kinase deficiency?

A

PK is a enzyme in glycolysis. Deficiency causes reduced ATP production in the red blood cell and increased 23DPG –> Causes Hb to have a lower affinity for oxygen

110
Q

What are the clinical features of PK deficiency?

A
  • Congenital haemolytic anaemia, can also present later in life
  • Variable chronic haemolysis
  • Prone to aplastic crisis in Parvovirus B19 Infection
  • Classical features of hameloysis on investigation inc high reticulocyte count
111
Q

Definitive diagnosis of PK deficiency requires??

A

PK level

112
Q

Tx of Pyruvate Kinase deficiency?

A
  • Folic acid
  • Transfuse during severe crisis
  • Consider splenectomy if high transfusion requirements
113
Q

What does FBC include?

A

o Haemoglobin
o MCV – mean cell volume (how big rbc)
o Haematocrit – what proportion of blood volume is made up of rbc
o Platelets – count

o	White cell count - overall
o	Neutrophils
o	Lymphocytes
o	Monocytes 
o	Basophils
o	Eosinophils
114
Q

What is the normal haematocrit?

A

About 45%

115
Q

What happens to haematocrit in polycythaemia?

A

Rises

116
Q

When does neutrophil count increase?

A

Infection and inflammation

117
Q

Where does haematopoiesis normally occur?

A

Bone marrow – confided to central skeleton and proximal ends of the long bones

118
Q

What is extramedullary haematopoiesis?

A

Cells that make RBCs form colonies elsewhere in the body e.g spleen – could contribute to splenic enlargement

119
Q

What is the haematopoetic stem cell?

A

Can self renew and differentiate into progenitor cells

120
Q

2 routes of the haematopoietic stem cell?

A

Early commitment to either: Lymphoid or myeloid route

121
Q

How is haematopoiesis regulated?

A

By cytokines : EPO, G-CSF,GH, IL-2, TPO

122
Q

EPO is illegally used in what group of people?

A

Performance enhancing drug by elite sports people – cyclers

123
Q

What is the important signalling pathway in haematopoiesis?

A

JAK/STAT signalling

124
Q

How does JAK/STAT signalling work?

A

Act on cell surface receptors –>activate the JAK/STAT signalling pathway –>activates the inactive enzymes by phosphorylation–> cascade–> changes in gene transcription – switches on genes involved in cell proliferation

125
Q

JAK/STAT signalling goes wrong in what group of disorders?

A

Myeloproliferative neoplasms

126
Q

What signalling pathway goes wrong in MPNs?

A

JAK/STAT

127
Q

What are Myeloproliferative neoplasms?

A

Group of blood cancers, generally considered to be chronic conditions and can evolve over many years. Characterised by uncontrolled proliferation of one or more cell lines in the bone marrow – usually: eryhthroid, myeloid and/or megakaryocyte lines

128
Q

What is the main manifestation of MPNs?

A

Accumulation of mature blood cells in the circulation – that arise from haematopoietic stem cells. The cells look normal

129
Q

Cause of MPNs?

A

Something has gone wrong in the haematopoietic stem cells – acquisition of genetic mutations in haematopoietic stem cells –> JAK/STAT signalling ‘switched on’ inappropriately

130
Q

Are MPNs inherited or aquired?

A

Aquired

131
Q

In MPNs, what are the mutations in?

A
  • CALR- calreticulin: lots of receptors clumped together –> swtiches on even without cytokine
  • MPL: point mutations –>change 3d shape of receptor–> permanently on
  • JAK2V617F: kinase – enzyme that phosphorylates –> mutation–> no auto-inhibition–>permanently active and phosphorylating
132
Q

What diseases are MPNs?

A
  • Polycythaemia Vera (PV)
  • Essential Thrombocytosis (ET
  • Myelofibrosis (MF)
  • Chronic Myeloid Leukemia (CML)
  • Rare MPNs (chronic neutrophilic leukemaia, eosinophilic leukaemia)
133
Q

What is Polcythaemia Vera (PV)?

A

Clonal stem cell disorder in which there is an excessive proliferation of erythroid, myeloid and/or megakaryocytic progenitor cells.
-Elevated haematocrit and Hb – may have splenomegaly. Too much RBC.

134
Q

What is the most common mutation in Polycythaemia Vera?

A

JAK2 (over 95%). Point mutation that causes the substitution of phenylalanine–> valine at position 617 – JAK2V617F

135
Q

Describe the onset of disease in Polycythaemia Vera?

A

Insidious

136
Q

What age group is Polycythaemia Vera most common in?

A

> 60

137
Q

Clinical presentation of Polycythaemia Vera?

A 
o	Fatigue
o	Itching
o	Vertigo 
o	Headache
o	Visual disturbance
o	Complications of the disease – thrombosis or haemorrhage

Since these symptoms are common in the older population , diagnosis of PV is commonly missed

138
Q

What is the main complication of Polycythaemia Vera?

A

Blood clots –>risk of stroke, MI, DVT .

139
Q

What is disease transformation?

A

Relatively chronic indolent disease–> switches to aggressive acute leukemia/ myeloid fibrosis. Occurs in small proportion

140
Q

What is the disease transformation like in Polycythaemia Vera?

A
  • 12-21% develop into myeloid fibrosis

- 5% develop into AML

141
Q

Median prognosis in Polycythaemia Vera?

A

13 yrs

142
Q

Causes of elevated haematocrit?

A
  • Primary PV

- Secondary: lung disease, alcohol, ‘apparent erythrocytosis’, EPO producing tumours, COPD patients

143
Q

What is apparent erythrocytosis?

A

Not too many RBC, just not enough liquid -dehydrated, SGLT-2 inhibitors

144
Q

What tumours can produced EPO?

A

Rare – liver and kidney cancer

145
Q
  1. How do you differentiate between secondary causes and primary PV?
A

Spleen is palpable in 70% in Primary PV

146
Q
  1. What is the diagnostic criteria for PV?
A

o JAK-2 Positive PV: requires mutation in JAK-2 + elevated haematocrit or raised red cell mass
o JAK-2 Negative PV: Just look at BSH guidelines (basically exclude secondary causes + look for other signs/ symptoms, other blood evidence)

147
Q

What is the aim of Tx in Polycythaemia Vera?

A

Maintain normal blood count and prevent complications of disease particularly thromboses and haemorrhage. Aim to keep haematocrit <0.45

148
Q

What is the management of Polycythaemia Vera?

A

Focus to reduce risk of blood clots:
• Venesection: inital removal of 400-500mL of blood weekly–> relieves symptoms, aim of haematocrit <0.45
• Hydroxycarbamide – mild chemotherapy continuous or intermittent. Reduces RBC production. Used in patients who do not tolerate venesection or have poorly controlled features – e.g thrombocytosis, symptomatic splenomegaly or thrombosis
• Low dose Aspirin: 75mg daily with the above Tx is routinely given in patients with PV in the absence of contraindications
• Management of other CV risk factors: BP control ,cholesterol, diabetes: need to have an annual check

149
Q

When is Allopurinol given in PV?

A

If they have gout, allopurinol blocks uric acid production. Gout is due to increased cell turnover

150
Q

In patients with PV, what should be done before surgery?

A

PV should be controlled. High operative risk. In emergency, haematocrit must be reduced by venesection and appropriate fluid replacement

PHASE 2A MEDICINE - ANJALI createdd (9 decks)

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