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House Hemat > Haemoglobin Disorders I > Flashcards

Haemoglobin Disorders I Flashcards

1
Q

What are the haemoglobinopathies?

The haemoglobinopathies are a group of disorders passed down through ___________ in which there is __________ or __________ of the haemoglobin molecule.

A

families (inherited)

abnormal production or structure

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2
Q

What are the haemoglobinopathies?

Haemoglobinopathies are caused by mutations in _________, which encode for the _________ of haemoglobin, causing decreased or defective production of ________,___________ and ________

A

globin genes

globin proteins

haemoglobin, haemolysis, and anaemia.

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3
Q

_____________ are the commonest monogenic diseases because almost ___% of the worldwide population are carriers.

A

Haemoglobinopathies

7

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4
Q

What are the haemoglobinopathies?

They have originally emerged from the _______ regions, large parts of ———— and ______ .

However, the ————- and _________ contributed to their spread from those areas to all over the world.

A

Mediterranean

Asia and Africa

slave trade and international migration

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5
Q

Classification of Haemoglobin Disorders

Haemoglobin disorders are be broadly classified into two general categories

__________ disorders of globin _________

_________ disorders of globin chain _________

A

Qualitative; structure

Quantitative; synthesis/accumulation

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6
Q

Geographic distribution of the haemoglobinopathies

Commonest genetic defect worldwide with an estimated _________ carriers.

Inherited haemoglobin disorders were originally characteristic of the ______ and ______ but are now common worldwide due to migration.

A

269 million; tropics and subtropics

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7
Q

Geographic distribution of the haemoglobinopathies

In populations in which _______ is (or was) endemic, 3 to 40% of individuals carry one of these significant variants.

A

malaria

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8
Q

Geographic distribution of the haemoglobinopathies

Haemoglobin disorders are distributed across South-east Asia in a line stretching from _______ down the___________ to __________

A

Southern China

Malaysian Peninsula

Indonesian islands.

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9
Q

Hb AS is very widespread and is found in up to one in _____ West Africans, (______%).

It is maintained at this level because of _______________________

A

four; 25

the protection against malaria that it offers.

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10
Q

Hb AS

Also distributed across the Mediterranean, Middle East, and Indian Subcontinent.

T/F

A

T

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11
Q

Hb AS

The distribution of the defect is thought to be due to ___________________________________

A

partial protection for carriers from plasmodium falciparum malaria.

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12
Q

β thalassaemia syndrome is found in the ———— region especially Greece, Italy, some part of Spain

While

α-thalassaemia is more common in the _______/________.

A

Mediterranean

Far East/ South-east Asia

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13
Q

The world distribution of haemoglobinopathies overlaps the geographic distribution of malaria.

T/F

A

T

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14
Q

It is believed that carriers of α thalassaemia are protected against malaria

T/F

A

T

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15
Q

It is believed that carriers of ___ thalassaemia are protected against malaria

A

α

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16
Q

It is believed that carriers of α thalassaemia are protected against malaria and that _______ is responsible for elevating and maintaining their gene frequencies.

A

natural selection

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17
Q

The most common inherited Hb disorder:

α plus (α+) thalassaemia, is usually (harmful or harmless?) .

However, people who inherit combinations of haemoglobins ______,____,_____,______,______, or ________ may have a serious haemoglobin disorder.

A

harmless

S, C, E, D Punjab, β thalassaemia, or α zero (α0) thalassaemia

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18
Q

The most common inherited Hb disorder:

___________________ is the most common

A

Homozygous sickle cell anaemia (Hb SS)

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19
Q

The most common inherited Hb disorder:

the doubly heterozygote conditions of ________ and _______ also cause sickling disease.

A

Hb SC and Hb Sβthal

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20
Q

The most common inherited Hb disorder:

Haemoglobin C defect is most frequent in ______. The highest frequency is found in _______ and _______ followed by ________ part of ______.

This is due to the fact that these areas were or are still afflicted with ______

A

West Africa

Burkina fasso & Ghana

western part of Nigeria

malaria

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21
Q

Hb C confers a relative protection against malaria.

T/F

A

T

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22
Q

Types of genetic defects causing Haemoglobinopathies

o________ of a globin gene
o__________ of a globin gene
o_______ of genes
oProduction of ________
oAbnormal ____________
o_________ resulting in dysfunction of the genes
oMutations affecting ____________giving rise to elongated but unstable globin chain.

A

Deletion

Partial deletion

Fusion

non-functional mRNA

gene transcription

Point mutations

termination of translation

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23
Q

Types of genetic defects causing Haemoglobinopathies

The most common genetic disorder of haemoglobin is those caused by _______ followed by _________.

A

point mutation

deletion

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24
Q

Thalassaemia

_____________ of _________◦β thalassaemia

________ of ________◦α thalassaemia

Other variant

A

Reduced production of β chains

Reduced production of α chains

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25
Q

β-Thalassaemia

__________ deficiency

  • So reduced Hb ____

BUT retained production of other β-type chains, so increased
◦_______ production (Hb____)
◦_______ production (Hb_____)

A

β chain

A

Delta (δ) ; A2

gamma (γ ) ; F

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26
Q

β thalassaemia

β gene Encoded by _____ gene pair

(Xlinked or Autosomal?) (recessive or dominant?)

A

a single ; Autosomal; recessive

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27
Q

β thalassaemia

Heterozygotes have β thalassaemia ______

A

trait

MAJOR

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28
Q

β thalassaemia

they are (ALIVE or DEAD?) at birth

A

ALIVE

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29
Q

Inheritance of β thalassaemia

β-thalassemias are caused by ________ or, more rarely, ______ in the β globin gene on chromosome ____, leading to ____ (β+) or ______ (β0) synthesis of the β chains of hemoglobin (Hb).

A

point mutations

deletions

11

reduced

absent

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30
Q

Inheritance of β thalassaemia

Transmission is (Xlinked or autosomal?) (dominant or recessive?)

A

Autosomal

recessive

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31
Q

Inheritance of β thalassaemia

dominant mutations have also been reported.

T/F

A

T

32
Q

β thalassaemia genes

If the mutation causes total shutdown of the β chain production
◦No β chain produced: _____

If the mutation reduces β chain production (but does
not shut it down)
◦some β chain produced : ______

A

β0

β+

33
Q

Genetic combinations

β / β+ _____zygote ◦____cytosis,
◦Hb _____ ◦raised _____ and _____

β / β0 _____zygote
◦____________cytosis,
◦Hb _______ ◦raised _____ and _____

A

hetero; Micro; normal; A2 and F

hetero; More severe micro; normal; A2 and F

34
Q

Genetic combinations

β +/β+ ◦_____cytosis,
◦——- anaemia

β +/ β0
_____________◦____cytosis, ____ anaemic
◦
β 0/ β0
◦____________: _______ dependent ◦_______ cytosis, _____ changes,

A

micro; +/-

thalassaemia intermedia; micro ; variably

Thalassaemia Major; transfusion; micro

red cell

35
Q

thalassaemia intermedia is when ????

thalassaemia major is when?

A

One gene is not producing beta chain Atall and the second gene is producing a reduced amount of beta chain

Both genes are shut down

36
Q

Clinical features of β Thalassaemia

Severe anaemia becomes apparent at _________ after birth when __________________ should take place.

A

3-6 months

the switch from γ- to β-chain production

37
Q

Clinical features of β Thalassaemia

Enlargement of the liver and spleen occurs as a result of ___________,_________ and later because of ________.

A

excessive red cell destruction

extramedullary haemopoiesis

iron overload

38
Q

Clinical features of β Thalassaemia

The large spleen increase blood requirements by ___________ and _________, and by causing ____________

A

increasing red cell destruction and pooling

expansion of the plasma volume.

39
Q

Clinical features of β Thalassaemia

_________ but not as much as in SCD.

A

Jaundice

40
Q

Clinical features of β Thalassaemia

Expansion of bones caused by ______________ leads to a thalasaemic ______: _________,________,_________ and to thinning of the cortex of many bones with a tendency to fractures and bossing of the skull with a ‘___________’ appearance on X-ray.

A

intense marrow hyperplasia

facies

mongoloid, gnathopathy, small stature

hair-on- end

41
Q

Clinical features of β Thalassaemia

The patient can be sustained by _________ , but _______ caused by repeated transfusions is inevitable unless _________ is given.

A

blood transfusions

iron overload

chelation therapy

42
Q

Clinical features of β Thalassaemia

Each 500ml of transfused blood contains approximately _____mg iron.

To make matters worse, _____________________ is increased in β-thalassaemia, probably secondary to _______________ and inappropriately low serum _______ levels.

A

250

iron absorption from food

ineffective erythropoiesis

hepcidin

43
Q

Clinical features of β Thalassaemia

Iron damages the liver and the endocrine organs with failure of ______, delayed or absent _____, ______,______, and _________

A

growth

puberty

diabetes mellitus, hypothyroidism and hypoparathyroidism

44
Q

Clinical features of β Thalassaemia

Skin pigmentation as a result of _______ and _________ gives a ________ appearance at an early stage of iron overload.

A

excess melanin and haemosiderin

slately grey

45
Q

Clinical features of β Thalassaemia

Most importantly, iron damages the ____.

In the absence of intensive iron chelation, death occurs in the ______ or _____ decade, usually from _______ or ________

A

heart

second or third

congestive heart failure or cardiac arrhythmias.

46
Q

Clinical features of β Thalassaemia

Infections can occur for a variety of reasons.

In infancy, without adequate transfusion, the anaemic child is prone to _____ infections.

_____,________, and _______ infections are likely if _______ has been carried out and ___________ is not taken.

A

bacterial

Pneumococcal, Haemophilus and meningococcal

splenectomy

prophylactic penicillin

47
Q

Clinical features of β Thalassaemia

Transfusion of viruses by blood transfusion may occur

T/F

A

T

48
Q

Clinical features of β Thalassaemia

Liver disease in thalassaemia is most frequently a result of _______ but _______ is also common where the virus is endemic.

__________________ has been transmitted to some patients by blood transfusion.

A

hepatitis C

hepatitis B

Human immunodeficiency virus (HIV)

49
Q

Clinical features of β Thalassaemia

Osteoporosis may occur in well-transfused patients. It is more common in _______ patients with ______ abnormalities and with __________ resulting from ineffective erythropoiesis.

A

diabetic; endocrine

marrow expansion

50
Q

Clinical features of β Thalassaemia

Growth ________, delayed ________________

A

retardation

secondary sexual characteristics.

51
Q

Laboratory Diagnosis of β Thalassaemia

There is a severe ____chromic, ____cytic anaemia, _____ reticulocyte percentage with normoblasts, ______ cells and _________ in the blood film.

A

hypo; micro ; raised

target; basophilic stippling

52
Q

Laboratory Diagnosis of β Thalassaemia

Haemoglobin electrophoresis reveals absence or almost complete absence of Hb ______, with almost all the circulating haemoglobin being Hb ____.

The Hb ——- percentage is normal, low or slightly raised in β thalassaemia.

A

Hb A; Hb F

Hb A2

53
Q

Laboratory Diagnosis of β Thalassaemia

________________ is now usually used as first-line method to diagnose haemoglobin disorders.

_______ is used to identify the defect on each allele.

A

High performance liquid chromatography

DNA analysis

54
Q

Blood film in B-thalassemia

——chromic

——-cytic

_____ cells

——— red cells( _______)

_________ are seen in the same red cells

A

Hypo; micro

Target

Nucleated; normoblasts

Howell-jolly

55
Q

Management of beta thalassemia

___________ are needed to maintain the haemoglobin over ___g/dL at all times. This usually requires ________ units every ————-

 Fresh blood, filtered to __________, gives the best red cell survival with the fewest reactions.

 Regular ______ (e.g. 5 mg/day) is given if the diet is poor.

A

Regular blood transfusions; 10

2-3 units; 4-6 weeks.

remove white cells

folic acid

56
Q

Management of beta thalassemia

_____ therapy is used to treat iron overload. The most established drug is _________. The complex is mainly excreted in the _____ but up to one-third is also excreted in the ______.

A

Iron chelation

deferroxamine

urine; stools

57
Q

Oral Iron chelators are not available.

T/F

A

F

Oral Iron chelators are now available.

58
Q

Management of beta thalassemia

________, 200mg/day, increase excretion of iron produced by deferoxammine.

———— may be needed to reduce blood requirements.

A

Vitamin C

Splenectomy

59
Q

Management of beta thalassemia

________ therapy is given either as replacement because of end-organ failure or to stimulate the pituitary if puberty is delayed.

A

Endocrine

Diabetics

calcium and vitamin D

biophosphonate

60
Q

Splenectomy should be delayed until the patient is over ____ years old because of the high risk of dangerous infections post-splenectomy. The vaccinations and antibiotics to be given.

A

6

61
Q

Management of beta thalassemia

Immunization against _______ should be carried out in all non-immune patients.

A

hepatitis B

62
Q

Management of beta thalassemia

__________________ offers the prospect of permanent cure.

The success rate (long-term thalassaemia major-free survival) is over ____% in well- _______ (younger or older?) patients without _______ or ________

A

Allogeneic bone marrow transplantation

80

chelated; younger

liver fibrosis or hepatomegaly.

63
Q

Management of beta thalassemia

A human leucocyte antigen (HLA) matching ______ (or rarely other family member or matching unrelated donor) acts as donor. Failure of transplant can happen resulting in recurrence of thalassaemia or death

A

sibling

64
Q

Inheritance of alpha thalassaemia

More complex as encoded by ___ gene pairs (so ___ genes per person, not ___)

A

2; four; two

65
Q

alpha thalassaemia trait (α+ )

____ gene deletion : (____)

_________

_______ Hb

_________ or _________ MCV

A

One

α α/ α-

Silent carrier

normal

normal or slightly reduced

66
Q

Cis- _____ gene deletion: (_____/_____)

_______

_______ anaemia

MCV ______, RBC count is _____ x 1012/L.

Hb electrophoresis is _______,
DNA analysis needed for diagnosis

A

Two

α α /- -

α0 trait; Usually no

low; >5.5

normal

67
Q

Trans- ____ gene deletion: (_____/____)

Homozygous __________

_______ anaemia

MCV ______, RBC count is _____ x 1012/L.

Hb electrophoresis is _______,
DNA analysis needed for diagnosis

A

Two

α -/ α-

thalasaemia trait

Usually no

low; >5.5

normal

68
Q

Three gene deletion: (_____/______)

•___________ disease,

•______ Hb, Hb 7-11g/dl ,

•may or may not be __________

•unlike in beta thalassaemia, there is ________ for alpha

A
  • -/α -

Haemoglobin H

Reduced

transfusion dependent

no substitute

69
Q

Three gene deletion: (- -/α - )

•_____cytic _____chromic anaemia, fragmented cells, _____ cells , ________, _____cytosis

A

micro; hypo

target; polychromasia

poikilo

70
Q

Three gene deletion: (- -/α - )

•_____megaly

presence of ________________ on film
(“_______” cells)

A

spleno

beta tetramers β4 (HbH)

golf ball

71
Q

_____________

Four gene deletion: (______/____) Four gene deletion
◦___ alpha chain production
◦ ________ with life
◦ fetus _______
◦_________ form instead γ4- Hb Barts

A

Barts Hydrops fetalis

  • -/ - -

no

incompatible

dies in utero

gamma tetramers

72
Q

With regards to haemoglobinopathies?

A) alpha thalassaemia are caused by deletions in the alpha globin gene

B) beta thalassaemia is not clinically apparent until 6 months of age

C)HbS forms as a result of a point mutation in codon 7 of the beta globin gene

D)sickle cell disease is the commonest genetic disorder in Nigeria

E) they are blood cell disorders which cause haemolytic anaemia

A

C

73
Q

Caused by deletion of all four alpha globin genes ?

A) beta thalassaemia major

B) Hb Barts hydrops fetalis

C) Diamond-Blackfan anaemia

D)alpha thalassaemia trait

E)hereditary spherocytosis

A

B

74
Q

Deletion of one or two alpha globin genes?

A) Hereditary spherocytosis

B) Hb Barts hydrops fetails

C) Diamond-Blackfan anaemia

D) alpha thalassaemia major

E)alpha thalassaemia trait

A

E

75
Q

Concerning β thalassaemia

A) Mutations reduce or eliminate the production of β-globin chains.

B)Gene deletions may cause β thalassaemias but are more common in α thalassaemia

C)Either no β chain (βo) or small amounts (β+) are synthesized.

D)The main pathology involved is excess β chains which precipitate in erythroblasts and in mature red cells causing the severe ineffective erythropoiesis and haemolysis that are typical of the disease.

E)Production of γ-chains helps to ‘mop up’ excess α chains and to ameliorate the condition.

A

I don’t know

76
Q

As regard the α-Thalassaemia Syndromes

They are usually caused by gene deletions.

The clinical severity depends on the number of genes that are missing or inactive.

Loss of all four α genes is compatible with life.

Hb H disease (β4) is three α gene deletions and leads to moderately severe microcytic, hypochromic anaemia with splenomegaly.

In foetal life, Hb Barts (γ4) occurs when all four α genes are deleted. α-thalassaemia traits are caused by loss of one or two genes

A
77
Q

The following may be clinical manifestation of β-Thalassaemia

Growth retardation and delayed secondary sexual characteristics.

Leucocytosis

Bleeding tendency

Tendency to fractures and bossing of the skull with a ‘hair-on-end’ appearance on X-ray.

Skin pigmentation

A

T

F

F

T

T

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