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8. CP - Core Haematology > (39) Obstetric haemoglobinopathy > Flashcards

(39) Obstetric haemoglobinopathy Flashcards

1
Q

Describe the appearance of normal erythrocytes

A
  • bi-concave discs

- no nucleus

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2
Q

What is the function of normal erythrocytes?

A

To transport oxygen bound to haemoglobin

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3
Q

The production of erythrocytes is controlled by what?

A

Erythropoietin (EPO) produced in the kidneys in response to tissue oxygen concentration

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4
Q

Which organ produces erythropoietin?

A

The kidneys

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5
Q

Describe haemoglobin

A

Tetramer of globin chains, each non-covalently bound to a Haem

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6
Q

What types of globin chains do normal haemoglobins have?

A

All normal haemoglobins have 2 alpha and 2 non-alpha chains

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7
Q

Which globin chains does Hb-A consist of?

A

2 alpha and 2 beta

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8
Q

Which globin chains does Hb-F consist of?

A

2 alpha and 2 gamma

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9
Q

Which globin chains does Hb-A2 consist of?

A

2 alpha and 2 delta

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10
Q

What is the function of globin in haemoglobin?

A
  • protects haem from oxidation
  • renders the molecule soluble
  • permits variation in oxygen affinity
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11
Q

Which chromosome controls the production of alpha chains?

A

Chromosome 16

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12
Q

Which chromosome controls the production of gamma, delta, and beta chains?

A

Chromosome 11

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13
Q

Which globin chains in Hb-F made up of?

A

2alpha/2gamma

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14
Q

Which globin chains is Hb-A made up of?

A

2alpha/2beta

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15
Q

Which globin chains is Hb-A2 made up of?

A

2alpha/2delta

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16
Q

What are the proportions to the different type of haemoglobin in normal adult blood?

A
  • Hb-A = over 95%
  • Hb-A2 =less than 3.5%
  • Hb-F = less than 1%
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17
Q

What do haemoglobinopathies mean?

A

Changes in globin genes or their expression which leads to disease

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18
Q

Give 2 types of haemoglobinopathy

A
  • structural Hb variants eg. sickle cell

- thalassaemias

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19
Q

What are the different types of structural Hb variants?

A
  • Hb S (sickle)
  • Hb C
  • Hb D
  • Hb E
    etc
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20
Q

Structural Hb variants are usually caused by what mutation?

A

A single base substitution in globin gene leading to altered structure/function

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21
Q

What are the two types of thalassaemia?

A
  • alpha

- beta

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22
Q

What causes thalassaemias?

A

Change in globin gene expression leads to reduced rate of synthesis of NORMAL globin chains - therefore imbalance of alpha and beta chain production (free globin chains damage red cell membrane)

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23
Q

Give 2 types of maternal testing

A
  • genetic screening/counselling

- antenatal screening

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24
Q

What are the purposes of antenatal screening?

A
  • routinely offered in the UK
  • high risk pregnancies can opt for prenatal diagnosis (chorionic villus biopsy and genetic diagnosis at 8-12 weeks)
  • termination of affect pregnancies
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25
Q

What changes to red cells and plasma occur in pregnancy?

A
  • plasma volume expands in pregnancy by 50%
  • red cell mass expands by 25%
  • haemodilution occurs, maximally at 32 weeks
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26
Q

What is haemodilution?

A

Decrease in the proportion of red blood cells relative to the plasma, brought about by an increase in the total volume of plasma

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27
Q

The CDC define anaemia by what values in pregnancy?

A

Hb less than 11g/dL 1st and 3rd trimester, and less than 10.5g/dL in the 2nd trimester - anaemia must be investigated, Fe deficiency most common

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28
Q

What increases physiologically in pregnancy?

A

MCV increases

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29
Q

Pregnancy increases the requirements of what?

A
  • pregnancy increases requirements for iron and usually results in considerable mobilisation of Fe stores
  • pregnancy also increases folic acid requirements
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30
Q

What is leukocytosis?

A

An increase in the number of white cells in the blood

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31
Q

What leukocytosis occurs during pregnancy?

A

Mainly a neutrophilia

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32
Q

When does neutrophilia occur in pregnancy?

A

Rised from the 2nd month to a peak range of around 9-15 in the 2nd-3rd trimester

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33
Q

There may be a left shift in pregnancy. What does this mean?

A

High number of young, immature WBCs - sometimes due to infection so bone marrow produces more WBCs and releases them into blood before fully mature

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34
Q

What cells do you see in a left shift?

A

Immature neutrophils (band, metamyelocytes, myelocytes etc)

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35
Q

What is a myelocyte?

A

A young cell of the granulocytic series, occurring normally in bone marrow but can be found circulating in blood in certain diseases or states

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36
Q

Describe gestational thrombocytopenia

A
  • platelet count usually more than 70x10^9/l
  • platelet count falls after 20 weeks and thrombocytopenia is most marked in late pregnancy

8% of pregnant women

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37
Q

Is gestational thrombocytopenia a problem?

A
  • no pathological significance for mother or foetus
  • recovers rapidly following delivery
  • main issue in management is differentiation from other causes
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38
Q

What are the causes of thrombocytopenia in pregnancy in terms of pregnancy-associated production failure?

A
  • severe folate deficiency
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39
Q

What are the causes of thrombocytopenia in pregnancy in terms of pregnancy-associated consumption?

A
  • gestational
  • pre-eclampsia and HELLP syndrome
  • AFLP (acute fatty liver of pregnancy)
  • DIC eg. in abruption
  • TTP/HUS
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40
Q

What are the causes of thrombocytopenia in pregnancy in terms of coincidental production failure?

A
  • bone marrow infiltration/hypoplasia
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41
Q

What are the causes of thrombocytopenia in pregnancy in terms of coincidental consumption?

A
  • ITP (primary or secondary)
  • viral (HIV and EBV)
  • sepsis
  • type 2B vWD
  • hypersplenism
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42
Q

Pregnancy is a ….. state

A

Pro-thrombotic state

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43
Q

Describe the general ways in which pregnancy is a pro-thrombotic state

A
  • platelet activation
  • increase in procoagulant factors
  • reduction in some natural anticoagulants
  • reduction in fibrinolysis
  • rise in markers of thrombin generation
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44
Q

Describe the specific changes in coagulation factors during pregnancy

A
  • marked increase in plasma fibrinogen and factor VII
  • increase in factor V, VIII, X, XII
  • greater increase in vWF than factor VIII (2 fold in late pregnancy)
  • minimal increase in factor IX
  • small decrease in factor XI
  • initial increase in FXIII followed by reduction to approx 50% of non-pregnancy value
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45
Q

How do the levels of FVIII and vWF change during pregnancy?

A
  • increase in FVIII

- greater increase in vWF than factor VIII (two fold in late pregnancy)

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46
Q

What happens to factor 13 levels during pregnancy?

A

Initial increase followed by reduction to approximately 50% of non-pregnant value

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47
Q

Worldwide distribution of haemoglobin disorders mirrors which disease?

A

Falciparum malaria

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48
Q

Structural Hb variants can usually be detected by what?

A

Abnormal mobility on HAEMOGLOBIN ELECTROPHERESIS

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49
Q

How does haemoglobin electrophoresis work in the diagnosis of haemoglobinopathies?

A

Uses an electrical current to separate normal and abnormal types of haemoglobin in the blood. Hemoglobin types have different electrical charges and move at different speeds. The amount of each hemoglobin type in the current is measured

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50
Q

Can thalassaemias be diagnosed by haemoglobin electrophoresis?

A

Thalassaemias have normal Hb electrophoresis by small pale red cells (microcytic and hypochromic) can be seen resembling iron deficiency

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51
Q

What are the many different ways of diagnosing haemoglobinopathies?

A
  • FBC/blood film
  • haemoglobin electrophoresis
  • isoelectric focusing
  • high performance liquid chromatography (HPLC)
  • heat stability (isopropanol test for unstable Hbs)
  • oxygen dissociation curve
  • DNA analysis
  • mass spectrometry
  • Kleihauer testing, Supravital staining, Sickle solubility
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52
Q

What is the Kleihauer-Betke test?

A

Blood test used to measure the amount of fetal hemoglobin transferred from a fetus to a mother’s bloodstream

  • usually performed on Rh-negative mothers to determine the required dose of Rho(D) immune globulin (RhIg) to inhibit formation of Rh antibodies in the mother and prevent Rh disease in future Rh-positive children
  • The KB test is the standard method of quantitating fetal-maternal hemorrhage (FMH).
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53
Q

What is supravital staining?

A

A method of staining used in microscopy to examine living cells that have been removed from an organism. It differs from intravital staining, which is done by injecting or otherwise introducing the stain into the body

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54
Q

What is the basis of the sickle solubility test?

A

A mixture of HbS in a reducing solution such as sodium dithionite gives a turbid appearance because of precipitation of HbS, whereas normal haemoglobin gives a clear solution

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55
Q

What is the basis of the isopropanol test (IT) for unstable haemoglobins?

A

Hemolysate is incubated in a Tris buffer containing isopropanol. The less polar isopropanol buffer stresses the sulfhydryl bonds of the Hb molecule. Normal hemoglobins will not precipitate within 20min, while unstable hemoglobins will precipitate within 5 minutes.

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56
Q

What is isoelectric focusing?

A

A technique for separating different molecules by differences in their isoelectric point

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57
Q

Sickle cell disease was first diagnosed/named in which year?

A

1910

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58
Q

What is the difference in charge in Hb-S compared to normal?

A

Excess positive charge compared to healthy Hb

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59
Q

What is the base change and amino acid change that causes Sickle cell disease?

A

Single nucleotide substitution = A to T

GAG to GTG

Amino acid change = Glutamine to valine

at position 6 of the B-globin gene

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60
Q

What is it about Hb-S that causes the classical sickle shape?

A

Sickle Hb (Hb-S) polymerises at low oxygen tensions to form long fibrils (‘tactoids’) which distort the red cell membrane produce the classical sickle shape

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61
Q

Why does sickle cell disease lead to haemolytic anaemia?

A

The sickled red cells have a short lifespan in the blood - haemolytic anaemia

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62
Q

The polymerisation that occurs in Hb-S is reduced if what?

A

If other haemoglobins are present in the red cells eg. Hb-F in foetus or neonate

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63
Q

Why does haemolysis lead to haemostatic activation?

A
  • haemolysis releases haemoglobin into plasma = reduces NO
  • depletion of NO is associated with pathological platelet activation and tissue factor expression
  • also get phosphatidylserine exposure on red cells which can activate tissue factor and form platform for coagulation
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64
Q

What is sickle trait?

A

Heterozygous for sickle cell (HbA/HbS)

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65
Q

What is the blood count in sickle cell trait?

A

Normal

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66
Q

What is found in Hb electrophoresis in sickle cell trait?

A 
Hb-S = 45%
Hb-A = 55%
67
Q

Describe the general clinical picture in sickle cell trait

A

No problems except when extreme hypoxia/dehydration (eg. very bad anaesthesia, flying unpressurised military aircraft)

68
Q

Is the patient heterozygous or homozygous in sickle cell disease?

A

Homozygous (HbS/HbS)

69
Q

What is the blood count in sickle cell disease?

A

Anaemia (Hb 6-8g/dl)

70
Q

What is seen on blood film in sickle cell disease?

A

Sickle cells

71
Q

What is found on Hb electrophoresis in sickle cell disease?

A

Hb-S more than 95%

Hb-A 0%

72
Q

What is the frequency of sickle cell disease?

A
  • 1 in 200 Afrocaribeans
  • 1 in 60 West Africans
  • around 12,000 patients in UK (compared to 5,000 haemophilias)
73
Q

What are the acute complications of sickle cell disease?

A
  • vaso-occlusive crisis
  • septicaemia
  • aplastic crisis
  • sequestration crisis (spleen, liver)
74
Q

What is sickle cell crisis?

A

When the circulation of blood vessels is obstructed by sickled red blood cells, causing ischaemic injuries

75
Q

What are the different types of vaso-occlusive crisis in sickle cell disease?

A
  • acute chest syndrome (infarction of lung parenchyma)
  • pain in hands and feet (dactylitis)
  • priapism
  • abdominal pain
  • bones (long bones, ribs, spine)
  • brain
  • jaundice
76
Q

What is aplastic anaemia? (occurs as complication of sickle cell disease)

A

Temporary cessation of red cell production

77
Q

Sequestration crisis occurs when…

A

Intrasplenic sickling prevents blood from leaving the spleen and acute splenic engorgement ensues

78
Q

What are the chronic complications of sickle cell disease?

A
  • hyposplenism
  • renal disease
  • avascular necrosis (AVN) of the femoral and humeral heads
  • leg ulcers, osteomyelitis, gall stones, retinopathy, cardiac, respiratory
79
Q

Why can the patient get hyposplenism in sickle cell disease?

A

Due to infarction and atrophy of spleen

80
Q

What type of renal disease is a potential chronic complication of sickle cell disease?

A
  • medullary infarction with papillary necrosis
  • tubular damage = can’t concentrate urine (bed wetting at night)
  • glomerular: chronic renal failure/dialysis
81
Q

What is the mortality of sickle cell disease?

A

0.5% per annum in the UK

82
Q

How is vaso-occlusive crisis of sickle cell disease treated?

A
  • analgesia (usually opiates)
  • hydration (to maintain RBC water)
  • treatment of precipitants
83
Q

How is priapism in sickle cell disease treated?

A
  • education
  • acute: intracorporeal phenylephrine
  • chronic: etilefrine
84
Q

Why are children with sickle cell given penicillin from 6 months?

A

As prophlyaxis - more at risk of pneumococcal infection due to absent or non-functional spleens and decreased immune response

85
Q

What are the curative treatments of sickle cell disease?

A
  • bone marrow transplant from normal donor

- gene therapy

86
Q

What are the preventative measures taken in sickle cell disease?

A
  • genetic counselling/prenatal diagnosis

- avoiding precipitants

87
Q

What is done to measure respiratory symptoms in sickle cell disease?

A
  • ECHO screening

- O2 sats

88
Q

Why might top up transfusion be needed in sickle cell disease?

A
  • splenic sequestration
  • aplastic crisis
  • pre-operative
  • acute chest crisis (usually when Hb
89
Q

What is splenic sequestration?

A

An acute condition of intrasplenic pooling of large amounts of blood. Children with sickle cell disease between ages 5 months and two years represent most cases of splenic sequestration

90
Q

Why might exchange transfusion be needed in sickle cell disease?

A
  • acute chest crisis
  • acute stroke
  • pre-operative
  • chronic organ damage

regular exchange = primary and secondary stroke prevention

91
Q

Why is hydroxycarbamide used in sickle cell disease?

A

Hydroxycarbamide increases the amount of (HbF) in RBCs. HbF prevents blood cells from sickling.

92
Q

Giving hydroxycarbamide to sickle cell patients will reduce the severity of sickle cell
disease in some patients by…

A
  • increasing time RBCs survive = reduces anaemia and jaundice
  • reduces RBC adhesion to endothelium
  • reducing the number of neutrophils which can cause inflammation and trigger sickle
    cell crises
  • reducing the number of platelets (so less clotting)
  • enhances NO
93
Q

When should you consider using hydroxycarbamide in sickle cell disease?

A

If over 3 admissions with painful crisis in 12 months or 2 chest crises

94
Q

What is the STOP trial?

A

Stroke prevention in sickle cell anaemia - do a transcranial doppler annually from 3 years

95
Q

Why might a sickle cell patient need joint replacement?

A

For avascular necrosis (AVN) - do MRI

96
Q

Why might a sickle cell patient need cholecystectomy?

A

For symptomatic biliary disease

97
Q

Treatment of what other problems should be thought about in sickle cell disease patients?

A
  • transcranial doppler for stroke
  • MRI for avascular necrosis
  • perioperative care (transfusion, avoid local tourniquet)
  • cholescystectomy for biliary disease
  • renal disease
  • annual review for ophthalmic problems
    etc.
98
Q

The most common type of sickle cell disease is having 2 sickle cell genes (HbSS) but what are the other types?

A

Co-inheritance of one BS and another B chain abnormality eg.

  • HbSC
  • HbSO-Arab
  • HbS/B-thalassaemia
  • HbS/Lepore
  • HbS/D-punjab
  • HbS/HPFH
  • HbS/deltabeta0
  • HbS/E
99
Q

HbSC is the second most common type of sickle cell disease. How is it different to HbSS?

A
  • fewer crises
  • increased risk of AVN
  • increased risk of retinopathy
100
Q

Which are the severe types of sickle cell disease?

A

HbS/O-Arab

101
Q

Which are the moderate types of sickle cell disease?

A
  • HbS/beta-thalassaemia
  • HbS/Lepore
  • HbS/D-punjab
102
Q

What are the mild types of sickle cell disease?

A
  • HbS/HPFH
  • HbS/deltabeta0
  • HbS/E
103
Q

What are the thalassaemias?

A

Mutation in haemoglobin gene - to work normally, haemoglobin needs 2 alpha chains and 2 beta chains. The structure abnormal in thalassaemia

104
Q

What are the 2 broad types of thalassaemia?

A
  • alpha (mutation that affects alpha chain)

- beta (mutation that affects beta chain)

105
Q

How can the thalassaemias be divided?

A
  • alpha
  • beta
  • delta-beta
  • gamma-delta-beta

According to which globin chain is reduced

  • alpha0 = no alpha globin chain produced
  • a+ = alpha globin chain produced at reduced rate
106
Q

What is HPFH?

A

Hereditary persistence of foetal haemoglobin - foetal haemoglobin = 2 alpha chains and 2 gamma chains

107
Q

Which genes control alpha globin chains of haemoglobin?

A

4 genes, 2 on each chromosome 16, inherited as pairs

108
Q

Where are the most serious forms of alpha-thalassaemia restricted to?

A

SE Asia and some Mediterranean islands

109
Q

What is Hb Barts?

A

Homozygous inheritance of a0 (no alpha chains)

Hb Barts = consists of 4 gamma chains. It is moderately insoluble, and therefore accumulates in the red blood cells. It has an extremely high affinity for oxygen, resulting in almost no oxygen delivery to the tissues

110
Q

What will happen to a foetus with Hb Barts?

A

It will develop hydrops fetalis and normally die before or shortly after birth, unless intrauterine blood transfusion is performed

111
Q

What is hydrops fetalis?

A

Serious foetal condition defined as abnormal accumulation of fluid in 2 or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin oedema

112
Q

What is Hb H disease?

A

A moderate to severe form of alpha-thalassemia characterized by pronounced microcytic hypochromic haemolytic anaemia

Usually caused by inactivation of three alpha-globin alleles leading to underproduction of alpha-globin chains of Hb

113
Q

What is alpha-thalassaemia trait?

A

When 2 alpha globin genes (one on each chromosome 16) are mutated - there may be symptoms of mild anaemia

114
Q

What is B-thalassaemia?

A

Reduced rate of production of beta-globin chains (pathology caused by excess alpha chains)

115
Q

Carriers of beta-thalassaemia have what?

A

Thalassaemia minor - clinically normal

116
Q

Homozygotes of beta-thalassaemia have what?

A

Thalassaemia major - have a severe disease which is usually fatal if untreated - can produce little, if any, Hb-A and die of severe anaemia

117
Q

How does a blood film look in b-thalassaemia minor?

A

Resembles iron deficiency (small, pale red cells)

Target cells on film - Codocytes, also known as target cells or Mexican hat cells are red blood cells that have the appearance of a shooting target with a bullseye

118
Q

What are the Hb levels in b-thalassaemia minor?

A

Total Hb level normal or only slightly reduced

Hb-A2 level more than 3.5%

119
Q

What is the clinical picture in thalassaemia intermedia?

A
  • clinical picture and genetic basis highly variable
  • no absolute requirement for regular transfusions in order to survive during first 3-5 years of life
  • all should be genotyped
120
Q

What other conditions are related to beta-thalassaemia intermedia?

A
  • pulmonary hypertension
  • extramedullary haematopoiesis
  • bone changes and osteoporosis
  • endocrine and fertility (DM, hypothyroid)
  • leg ulcers
121
Q

What is DEXA?

A

Dual-energy X-ray absorptiometry - a means of measuring bone mineral density (BMD). Two X-ray beams, with different energy levels, are aimed at the patient’s bones. When soft tissue absorption is subtracted out, the BMD can be determined from the absorption of each beam by bone

122
Q

How does b-thalassaemia major present?

A

Presents with very severe anaemia at 1 to 2 years of age

123
Q

How does the blood film look in b-thalassaemia major?

A

Blood film very abnormal with lots of nucleated red cells

124
Q

What are the clinical features of b-thalassaemia major due to?

A

Due to severe anaemia and attempt to make more red cells in marrow to compensate

125
Q

What is extramedullary haematopoiesis?

A

Haematopoiesis occurring outside of the medulla of the bone

126
Q

Name 3 of the main types of pathology in B-thalassaemia major?

A
  • alpha chain excess
  • increased marrow activity
  • enlarged and overactive spleen
127
Q

What do alpha chain excess in B-thalassaemia major lead to?

A
  • ineffective erythropoiesis (red cells die in marrow)
  • shortened red cell lifespan (haemolysis)

= ANAEMIA

128
Q

What does increased bone marrow activity in B-thalassaemia major lead to?

A
  • skeletal deformity and stunted growth
  • increased iron absorption and organ damage (exacerbated by blood transfusion)
  • protein malnutrition
129
Q

What does enlarged and overactive spleen in B-thalassaemia major lead to?

A
  • pooling of red cells (increased anaemia)

- increased transfusion requirement

130
Q

Why do you get short stature and distorted limb growth in B-thalassaemia major?

A

Due to premature closing of epiphyses in long bones

131
Q

Why do you get an enlarged liver and spleen in B-thalassaemia major?

A

Due to extramedullary haemopoiesis

132
Q

Name 3 thalassaemic facies

A
  • maxillary hypertrophy
  • abnormal dentition
  • frontal bossing due to expanded bone marrow
133
Q

What does a head X-ray in B-thalassaemia major show?

A

Classical “hair on end” skull due to widening of diploid cavities by marrow expansion

134
Q

Why is transfusion used in the treatment of B-thalassaemia major?

A
  • to maintain mean Hb 12g/dl (pre-transfusion Hb 9.5-10)

- suppress marrow red cell production and prevent skeletal deformity and liver/spleen enlargement

135
Q

How often do B-thalassaemia major patients get blood transfusions?

A

3 to 4 weekly transfusions from 1st year of life

136
Q

What is the consequence of regular blood transfusions in B-thalassaemia major?

A
  • each unit of red cells contains 200-250mg of iron and the body has no excretory mechanism for iron
  • = severe iron overload and toxicity by 10-12 years of age
137
Q

B-thalassaemia major patients are at risk of iron overload due to regular blood transfusions. What are the consequences of this?

A
  • gonads/hypothalamus = failure of puberty, growth failure
  • pancreas = diabetes
  • heart = dilated cardiomyopathy and heart failure
  • liver - cirrhosis
138
Q

As well as iron overload, what are the other complications of blood transfusion?

A
  • transmission of infection

- allo-immunisation

139
Q

What is alloimmunisation?

A

An immune response to foreign antigens (alloantigens) from members of the same species. The body attacks mainly transplanted tissue and even the foetus in some cases.

allo = other 
auto = self (alloimmunity is different from autoimmunity)
140
Q

What are biggest causes of death in thalassaemia?

A
  • heart failure (60.2%)
  • infection (6.8%)
  • arrhythmia (6.8%)
141
Q

What is done to prevent iron overload in B-thalassaemia patients?

A

Patients are started on iron chelation therapy from 2nd year of life to promote excretion of iron in urine and faeces

142
Q

Name an iron chelator and how it is used

A

Desferrioxamine - given 8-12 hourly subcutaneous infusion via syringe-pump as home treatment on at least 5 nights per week to prevent accumulation of iron

143
Q

Name 2 new oral iron chelators

A
  • deferiprone

- deferasirox

144
Q

What is the target Ferritin level? (in iron chelator use)

A

1000-1500µg/L

145
Q

What are the different routes of administration in the different iron chelators?

A

DFO = SC, IV (8-12 hours, 5 days/week)

Deferiprone = oral (3 times daily)

Deferasirox = oral (once daily)

146
Q

What are the different ways of iron excretion in the different iron chelators?

A

DFO = urinary and faecal

Deferiprone = urinary

Deferasirox = faecal

147
Q

What is the benefit of DFO therapy?

A

Improves survival in regularly-transfused thalassaemia patients

148
Q

How is chelation monitored? (in B-thalassaemia major)

A
  • Ferritin (acute phase)
  • liver biopsy
  • MRI (T2)
149
Q

Why is there increased risk of infection in B-thalassaemia major?

A
  • decreased CD4/8 ratio
  • defective neutrophil chemotaxis
  • increased virulence with excess iron
  • line infections
  • transfusion transmitted infection
150
Q

What are the endocrine complications in B-thalassaemia major and their management?

A
  • growth and development
  • screening for glucose intolerance
  • hypothyroidism
  • hypoparathyroidism
151
Q

How are liver problems monitored in B-thalassaemia major?

A
  • LFT
  • ferritin
  • Hep serology
  • MRI

Hepatologist is established disease

152
Q

How are bone problems managed in B-thalassaemia major?

A
  • timely transfusion
  • no over-chelation
  • diet
  • hormone replacement of hypogonadism
  • monitoring for OP
  • treatment with biphosphonates
153
Q

How are fertility problems managed in B-thalassaemia major?

A
  • good chelation
  • fertility clinic advice
  • may need induction
  • cardiac, thyroid, diabetic and bone assessments
  • obstetric supervision
154
Q

What are the psycho-social aspects to treatment of B-thalassaemia major?

A
  • interpreters
  • written information
  • involvement in decisions (improves compliance)
  • regular child development review (may include clinical psychologist and social worker)
  • importance of MDT team
  • care networks - annual review at specialist centre
155
Q

What is the prognosis for patients with B-thalassaemia major?

A

Most patients now live into their 4th and 5th decades of life although many current patients still have high iron levels and there are significant “quality of life” issues

156
Q

What are the preventative methods against B-thalassaemia major?

A
  • genetic counselling (compulsory in some countries eg. Greek Cyprus has led to dramatic fall in incidence)
  • antenatal screening
  • neonatal screening (national programme from 2004)
157
Q

How is antenatal used in the detection of B-thalassaemia major?

A
  • routinely offered in UK
  • high risk pregnancies can opt for prenatal diagnosis (chorionic villus biopsy and genetic diagnosis at 8-12 weeks)
  • termination of affected pregnancies
158
Q

Explain the use of bone marrow transplantation in B-thalassaemia major treatment

A
  • from a tissue-type matched donor (usually a sibling)
  • only 1 in 4 siblings will be a match
  • 60-80% cure-rate if done in first few years of life but much less successful and high mortality if patients already has iron overload
159
Q

What is a potential future treatment for B-thalassaemia major?

A

Gene therapy

160
Q

What is an important note on the geographical distribution of B-thalassaemia major?

A

Over 95% of all patients with B-thalassaemia major live in the third world where even transfusion may not be available

161
Q

Summarise the 5 main physiological changes in pregnancy

A
  • anaemia (macrocytosis)
  • thrombocytopenia
  • neutrophilia (and left shift)
  • increased procoagulant factors
  • decreased fibrinolysis
162
Q

Sickle cell disease is a common autosomal recessive disorder of what?

A

The beta globin gene - forming an abnormal beta globin chain in haemoglobin

163
Q

In thalassaemia, the main focus is on good iron chelation to prevent what?

A

Cardiac and liver failure

8. CP - Core Haematology (11 decks)

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