Haem II (Thalassemia; Malaria) Flashcards

1
Q

Hodgkin’s Lymphoma is often preceded by infection of which virus

Parvovirus B19
COVID
CMV
EBV
Rhinovirus

A

Hodgkin’s Lymphoma is often preceded by infection of which virus

Parvovirus B19
COVID
CMV
EBV
Rhinovirus

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2
Q

Label the type of Hb that are dominant in each stage of life [3]

A

Yolk Sac / A: Z2, E2

Fetal liver / B: A2, γ2

Bone marrow / C: A2, B2

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3
Q

What are the normal variants of Hb? [3]

A
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4
Q

What is the inheritance patten of thalassaemias? [1]

A

Both alpha and beta conditions are autosomal recessive

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5
Q

Describe the different types of alpha thalassaemias [4]

A

Alpha thalassemia minima:
- 1 defective alpha subunit
- Silent carriers: slightly reduced / normal MCV but no clinical symptoms
- Hypochromic and microcytic anaemia

Alpha thalassemia minor:
- 2 defective alpha subunits
- Hypochromic and microcyticnaemia
- The remaining two alpha genes produce nearly normal levels of RBCs

HbH disease:
- 3 defective alpha subunits
- Excess beta chains causes RBC membrane damage and intramedullary haemolysis AND does not release oxygen to tissues, causing increased RBC production

Hydrops fetalis, Bart’s hydrops (γ4):
- 4 defective alpha subunits
- Extreme affinity to O2: incompatible with life

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6
Q

Describe the pathophysiology of the different forms of beta thalassamias [3]

A

The gene defects can either consist of abnormal copies (that retain some function) or deletion genes (with no function in the beta-globin)

Beta Thalassaemia minor:
- Mutation in one gene
- Reduced or no production of beta chains from one gene
- Other gene still functional
- Forms HbA
- Asymptomatic

Beta Thalassaemia intermedia
- Have two defective genes OR one defective gene and one deletion gene
- Causes more significant microcytic anaemia.

Beta Thalassaemia major
- homozygous for the deletion genes
- presents with severe anaemia and failure to thrive in early childhood
.

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7
Q

Describe the clinical presentation of a patient with thalassemia major [4]

A

The bone marrow is under so much strain to produce extra red blood cells to compensate for the chronic anaemia that it expands enough to increase the risk of fractures and change the patient’s appearance. Abnormal features relating to bone changes include:

  • Frontal bossing (prominent forehead)
  • Enlarged maxilla (prominent cheekbones)
  • Depressed nasal bridge (flat nose)
  • Protruding upper teeth
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8
Q

What is the management of thallassemia major? [4]

A

Management involves;
- regular transfusions
- iron chelation
- splenectomy
- A bone marrow transplant can be curative.

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9
Q

Write down the genotype of Beta thalassaemia minor, intermedia and major [3]

A

Minor: (b+/b OR b0/b)
Intermedia: (b+/b+)
Major: (b+/b0 OR b0/b0)

Mutation leading to absent production (0)
Mutation leading to reduced production (+)

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10
Q

Describe the difference in anaemia between B.T. minor and major [2]

A

Anaemia:
- Minor: usually asymptomatic with mild microcytic anaemia with haemoglobin counts > 100 g/L.
- Major: severe transfusion-dependent anaemia. Features of pallor, dyspnoea, dizziness, lethargy. Untreated, haemoglobin may be as low as 30-40 g/L.

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11
Q

Describe the bone deformities that can occur in B.T major [4]

A

Unusual bone formation:
* Facial deformities: frontal bossing, maxilla overgrowth, prominence of upper incisors, ‘chipmunk’ facies, dental malocculsion.
* Body habitus changes: typically short limbs due to early fusion of epiphyses. Skull, pelvis, ribs and spinal changes may be seen
* Osteopaenia/osteoporosis
* Bone pain

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12
Q

Describe how beta thalassaemia interacts with Fe levels in the body [2]

A

Ineffective erythropoiesis leads to an increase in iron absorption from the gastrointestinal tract that is compounded by regular blood transfusions.

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13
Q

Describe three further abnormalities associated with beta thal. [3]

A
  • Pulmonary: at risk of obstructive and restrictive defects. Some patients may develop pulmonary hypertension
  • Thrombotic: beta thalassaemia intermedia and major are associated with a hypercoagulable state.
  • Leg ulcers
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14
Q

Describe the diagnostic testing used to confirm the presence of beta thalassaemia [2]

A

Haemoglobin analysis:
- completed using haemoglobin electrophoresis or high-performance liquid chromatography (HPLC). Electrophoresis causes different types of haemoglobin to separate into bands. HPLC is an alternative method of determining the types of haemoglobin in blood.
- Patients with beta thalassaemia will have an increased proportion of HbA2 and HbF due to the absence of beta globin chains. Even in beta thalassaemia minor, there will be an elevation in HbA2.

Genetic testing:
- DNA testing provides a definite and precise diagnosis of beta thalassaemia. It is able to determine the type of mutation present.

Compared to alpha thal: just genetic testing

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15
Q

When does screening for beta thalassaemia occur? [1]

What result would indicate B.T? [1]

A

Antenatal screening is offered to all pregnant women within the UK. It involves concurrent assessment of different haemoglobinopathies (i.e. thalassaemia and haemoglobin variants) at 10 weeks gestation.

In beta thalassaemia, the level of HbA2 is quantified. Levels of HbA2 >3.5% is suggestive of being a beta thalassaemia carrier and further analysis of the father is required to determine the risk of beta thalassaemia in the fetus.

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16
Q

Describe the managment of beta-thalassaemia intermedia: non-transfusion-dependent [3]

A

1ST LINE:
- Transfusions at times of symptomatic anaemia
Patients with beta-thalassaemia intermedia do not usually require regular transfusions (non-transfusion-dependent thalassaemia). They are able to grow and develop at a nearly normal rate despite the moderate anaemia.
Occasionally, patients become severely anaemic and develop symptoms as a result. This usually occurs at times of major stress to the body, such as perioperatively, or during a serious illness or infection.

CONSIDER
- iron monitoring + chelation with desferrioxamine or deferasirox

PLUS
- genetic counselling

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17
Q

Describe the managment of beta-thalassaemia intermedia: transfusion-dependent AND beta-thalassaemia major [4]

A

1ST LINE:
- Regular transfusions

PLUS
- iron monitoring + chelation with desferrioxamine or deferasirox

PLUS
- genetic counselling

CONSIDER
- Splenectomy

CONSIDER
- Assessment for stem cell transplantation

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18
Q

Which drugs are used to manage iron overload? [3]
What is their MoA? [1]

A

Typical agents include Deferasirox, Deferoxamine and Deferiprone.

These chelators bind iron and increase excretion through urine and/or faeces.

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19
Q

Vaccinations agaisnt with pathogens are recommended in splenectomy patients? [4]

A

Vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus are strongly recommended.

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20
Q

Describe the management of hyposplenism [2]

A

In summary, the management can be considered to be two-fold:

Immunisations
- S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus

Antibiotic prophylaxis recommended in patients at high risk of pneumococcal infections
- oral phenoxymethylpenicillin or macrolides
- infection risk is highest in the initial years after splenectomy, all splenectomised patients are recommended to take daily antibiotic prophylaxis for the initial few years.

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21
Q

Name some pathologies that cause hyposplenism [5]

A

sickle cell anaemia (chronic damage to the spleen results in atrophy)
coeliac disease
dermatitis herpetiformis
essential thrombocythaemia
ulcerative colitis.

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22
Q

What are 4 blood film findings of hyposplenism [4]

A

Blood film: features of hyposplenism include Howell-Jolly bodies, Pappenheimer bodies, target cells and irregular contracted red blood cells.

23
Q

According to NICE guidelines, which diagnostic test is recommended for confirming the diagnosis of alpha thalassemia trait?
a) Hemoglobin electrophoresis
b) Molecular genetic testing
c) Complete Blood Count (CBC)
d) Serum Ferritin

A
24
Q

Alpha thalassemia can result from the deletion of alpha-globin genes. What is the most common alpha thalassemia genotype associated with clinical manifestations?
a) αα/αα
b) –/αα
c) –/–
d) α-/α-

A

Alpha thalassemia can result from the deletion of alpha-globin genes. What is the most common alpha thalassemia genotype associated with clinical manifestations?
a) αα/αα
b) –/αα
c) –/–
d) α-/α-

25
Q

In alpha thalassemia, the Hemoglobin H (HbH) disease results from the deletion of three alpha-globin genes. What is the recommended treatment for patients with HbH disease, according to NICE?

a) Blood transfusion
b) Hydroxyurea
c) Folic Acid supplementation
d) Hematopoietic stem cell transplantation

A

c) Folic Acid supplementation

26
Q

Individuals with alpha thalassemia trait (silent carrier) typically have two affected alpha-globin genes. How does NICE recommend managing asymptomatic individuals with alpha thalassemia trait during pregnancy?

a) Iron supplementation
b) Genetic counseling
c) Folate supplementation
d) Regular blood transfusions

A

Individuals with alpha thalassemia trait (silent carrier) typically have two affected alpha-globin genes. How does NICE recommend managing asymptomatic individuals with alpha thalassemia trait during pregnancy?

a) Iron supplementation
b) Genetic counseling
c) Folate supplementation
d) Regular blood transfusions

27
Q

For couples at risk of having a child with alpha thalassemia, what is the primary method of prenatal diagnosis recommended by NICE?

a) Amniocentesis
b) Chorionic villus sampling (CVS)
c) Non-invasive prenatal testing (NIPT)
d) Ultrasound

A

b) Chorionic villus sampling (CVS)

28
Q

NICE recommends screening for alpha thalassemia in newborns. What is the primary screening test used for this purpose?

a) Hemoglobin electrophoresis
b) Complete Blood Count (CBC)
c) DNA analysis
d) Serum Ferritin

A

NICE recommends screening for alpha thalassemia in newborns. What is the primary screening test used for this purpose?

a) Hemoglobin electrophoresis
b) Complete Blood Count (CBC)
c) DNA analysis
d) Serum Ferritin

29
Q

After the diagnosis of alpha thalassemia, what is the recommended frequency of follow-up monitoring for individuals with alpha thalassemia trait, according to NICE?

a) Every 6 months
b) Annually
c) Biennially
d) Only as needed based on symptoms

A

After the diagnosis of alpha thalassemia, what is the recommended frequency of follow-up monitoring for individuals with alpha thalassemia trait, according to NICE?

a) Every 6 months
b) Annually
c) Biennially
d) Only as needed based on symptoms

30
Q

According to NICE guidelines, which diagnostic test is recommended for confirming the diagnosis of beta thalassemia major?
a) Complete Blood Count (CBC)
b) Hemoglobin electrophoresis
c) Serum Ferritin
d) Molecular genetic testing

A

d) Molecular genetic testing

31
Q

In beta thalassemia major, NICE recommends regular blood transfusions to maintain hemoglobin levels. What is the target pre-transfusion hemoglobin level, according to NICE?
a) 8-9 g/dL
b) 9-10 g/dL
c) 10-11 g/dL
d) 11-12 g/dL

A

In beta thalassemia major, NICE recommends regular blood transfusions to maintain hemoglobin levels. What is the target pre-transfusion hemoglobin level, according to NICE?
a) 8-9 g/dL
b) 9-10 g/dL
c) 10-11 g/dL
d) 11-12 g/dL

32
Q

Individuals with beta thalassemia major are at risk of iron overload due to frequent transfusions. How often does NICE recommend monitoring serum ferritin levels for these patients?
a) Every 3 months
b) Every 6 months
c) Annually
d) Biennially

A

Individuals with beta thalassemia major are at risk of iron overload due to frequent transfusions. How often does NICE recommend monitoring serum ferritin levels for these patients?
a) Every 3 months
b) Every 6 months
c) Annually
d) Biennially

33
Q

To manage iron overload in beta thalassemia major, NICE recommends chelation therapy. Which chelator is commonly used in this setting?
a) Deferoxamine
b) Deferiprone
c) Desferrioxamine
d) Deferasirox

A

To manage iron overload in beta thalassemia major, NICE recommends chelation therapy. Which chelator is commonly used in this setting?
a) Deferoxamine
b) Deferiprone
c) Desferrioxamine
d) Deferasirox

34
Q

NICE recommends folate supplementation in beta thalassemia major. What is the purpose of folate supplementation in these patients?
a) Stimulate erythropoiesis
b) Prevent neural tube defects
c) Enhance iron chelation
d) Reduce oxidative stress

A

NICE recommends folate supplementation in beta thalassemia major. What is the purpose of folate supplementation in these patients?
a) Stimulate erythropoiesis
b) Prevent neural tube defects
c) Enhance iron chelation
d) Reduce oxidative stress

35
Q

In beta thalassemia major, allogeneic bone marrow transplantation is considered a curative option. What is a key requirement for a successful bone marrow transplant?
a) Age over 50 years
b) HLA-matched sibling donor
c) Presence of iron overload
d) Chronic liver disease

A

In beta thalassemia major, allogeneic bone marrow transplantation is considered a curative option. What is a key requirement for a successful bone marrow transplant?
a) Age over 50 years
b) HLA-matched sibling donor
c) Presence of iron overload
d) Chronic liver disease

36
Q

NICE suggests the use of hydroxyurea in beta thalassemia intermedia to reduce transfusion requirements. What is the mechanism of action of hydroxyurea in this context?
a) Stimulation of fetal hemoglobin
b) Inhibition of iron absorption
c) Prevention of bone marrow suppression
d) Induction of erythropoiesis

A

NICE suggests the use of hydroxyurea in beta thalassemia intermedia to reduce transfusion requirements. What is the mechanism of action of hydroxyurea in this context?
a) Stimulation of fetal hemoglobin
b) Inhibition of iron absorption
c) Prevention of bone marrow suppression
d) Induction of erythropoiesis

37
Q

tertian malaria (fever every other day) is caused by [2]

Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi

A

Plasmodium vivax
Plasmodium ovale

38
Q

subtertian malaria (fever < every 48hrs) is caused by

Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi

A

Plasmodium falciparum

39
Q

quartan malaria (fever spikes every 72 hours is caused by

Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi

A

Plasmodium malariae

40
Q

State 3 signs of malaria [3]

A

Pallor (anaemia)
Splenomegaly
Jaundice (due to haemolysis)

TOM TIP: The most characteristic symptom of malaria is the fever, which spikes very high every 48 hours. In someone with an unexplained fever, consider whether they have travelled somewhere with malaria present. Even exposure several years ago may be relevant, as P. vivax and P. ovale can lie dormant for up to 4 years.

41
Q

How do you diagnose malaria? [2]

A

malaria blood film:
- A malaria blood film will show the parasites, the concentration (as a percentage) and the type.

Three negative samples taken over three consecutive days are required to exclude malaria due to the parasites being released from red blood cells into the blood every 48-72 hours.

The sample may be negative when the parasites are not released but positive a day or two later when the red blood cells rupture and release the parasites.

42
Q

What is the protocol with admissions and Falciparum malaria? [1]

A

The local infectious diseases team will advise on management. All patients with falciparum malaria are admitted.

43
Q

What determines if malaria is uncomplicated or complicated? [3]

A

Criteria for uncomplicated malaria includes:
* Parasitaemia < 2%
* No schizonts on film
* No clinical complications

44
Q

Describe the management plan of uncomplicated P. falciparum malaria [2]

A

First-line options:
* Riamet (Artemether + lumefantrine): four tablets orally at 0, 8, 24, 36, 48 and 60 hours,
OR
* Malarone (atorvaquone + progunail): 4 tablets daily for 3 days

Second-line options:
* Quinine sulphate (600 mg TDS) + Doxycycline (200 mg OD): 7 days, OR
* Quinine sulphate (600 mg TDS) + Clindamycin (450 mg TDS): 7 days

45
Q

Describe the management plan of complicated P. falciparum malaria [3]

A

First-line options:
* Artesunate: 2.4 mg/kg intravenous at 0, 12, 24 hours then once daily. Always follow local guidelines on prescribing.
* If unavailable, may require quinine initially until artesunate is acquired.

Second-line options:
* Quinine dihydrochloride: Requires dose adjustment in renal and hepatic impairment and cardiac monitoring duration administration. Follow local guidelines.

Follow-on therapy (once improved and able to tolerate oral tablets):
* Riamet (Artemether + lumefantrine): four tablets orally at 0, 8, 24, 36, 48 and 60 hours, OR
* Doxcycline: 200 mg once daily for 7 days, OR
* Clindamycin: 450 mg three times a day for 7 days (preferred in pregnancy)

TOM TIP: Remember artesunate and quinine as treatment options for your exams, as these are the most likely to be relevant. Remember that Plasmodium falciparum is the most common and severe cause, and these patients should be admitted for artesunate treatment and monitoring for complications.

46
Q

Describe the treatment of of non-falciparum malaria or mixed [1]

A

Non-falciparum malaria should be discussed with microbiology and local guidelines followed.

Patients are usually able to be managed as outpatients.

Treatment is usually with chloroquine, but this depends on resistance patterns.

Follow-on treatment is typically required for P. vivax and P. ovale.

47
Q

Explain which genetic disorder you need to consider when treating malaria?

A

Glucose-6-phosphate deficiency (G6PD) (red cell lysis when erythrocytes are put under oxidative stress) because antimalarials, can induce red cell haemolysis.

Specifically:
* Primaquine (definite risk of haemolysis, G6PD needs to be excluded before use)
* Chloroquine (possible risk of haemolysis, acceptable in acute malaria)
* Quinine (possible risk of haemolysis, acceptable in acute malaria)

48
Q

Describe the complications of malaria

A

Severe malaria is invariably fatal if left untreated. Also:
Cerebral malaria (mortality of 50%)
ARDS
DIC
AKI
Severe anaemia
Septic shock
Splenic rupture
Multi-organ failure
Death

49
Q

Which medications can be used as prophylaxis for malaria [4]

A

Proguanil with atovaquone (Malarone)
Doxycycline
Mefloquine (risk of psychiatric side effects)
Chloroquine with proguanil (less often used due to high resistance)

50
Q

Name 3 side effects of doxycyline treatment [3]

A

diarrhoea
thrush
skin sensitivity to sunlight

51
Q

Which of the following is the most effective form of malaria prophylaxis

Doxycycline
Proguanil with atovaquone (Malarone)
Mefloquine
Chloroquine with proguanil

A

Which of the following is the most effective form of malaria prophylaxis

Doxycycline
Proguanil with atovaquone (Malarone)
Mefloquine
Chloroquine with proguanil

52
Q

Which of the following has a risk of pysc side effects

Doxycycline
Proguanil with atovaquone (Malarone)
Mefloquine
Chloroquine with proguanil

A

Mefloquine: causes anxiety, depression and abnormal dreams.

53
Q

What is a common side effect of artesunate treatment? [1]

A

haemolysis is a common side effect

54
Q

Vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus are strongly recommended for asplenic patients.

Which of the above is the most likely infection for asplenia? [1]

A

S. pneumoniae