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Haem extra cards > Thalassemia > Flashcards

Thalassemia Flashcards

1
Q

what is the normal concentration fo haemoglobin in adults

A

120-165g/L

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2
Q

describe when Hb synthesis occurs

A

Synthesis occurs during development of RBC and begins in pro-erythroblast:
65% erythroblast stage
35% reticulocyte stage

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3
Q

describe Hb structure

A

made of Haem + globin
Haem (synthesised in mitochondria)
Globin (synthesised in ribosomes)

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4
Q

how is haem synthesised

A

Combination of protoporphyrin ring with central iron atom (ferroprotoporphyrin)
Synthesised mainly in mitochondria which contain the enzyme ALAS
Iron usually in ferrous form (Fe2+)
Able to combine reversibly with oxygen

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5
Q

which other proteins contain haem

A

myoglobin, cytochromes, peroxidases, catalases, tryptophan

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6
Q

strcuture of heam

A

central Fe surrounded by protoporphyrin ring (connected by 4x Nitrogen connections)

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7
Q

synthesis of globin

A

Various types which combine with haem to form different haemoglobin molecules

Eight functional globin chains, arranged in two clusters:

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8
Q

what are the 2 clusters of globin chains

A

b- cluster (b, g, d and e globin genes) on the short arm of chromosome 11

a- cluster (a and z globin genes) on the short arm of chromosome 16

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9
Q

what are the normal Hb structures (composition and % in body)

A

Hb A α2β2 (96-98%)
Hb A2 α2δ2 (1.5-3.2%)
Hb F α2γ2 (0.5-0.8%)

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10
Q

how is glycated Hb detected

A

Each Hb type has a glycated fraction however only glycated HbA is normally present in sufficient quantity to be visible on a HPLC chromatogram and then only up to approximately 5%

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11
Q

Globin primary/secondary structure

A

Primary: α 141 AA
Non- α 146 AA
Secondary: 75% α and b chains-helical arrangement

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12
Q

Tertiary globin structure

A

Approximate sphere
Hydrophilic surface (charged polar side chains), hydrophobic core
Haem pocket

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13
Q

describe key features of Hb-oxygen dissociation curve

A

O2 carrying capacity of Hb at different pO2

Sigmoid shape
Binding of one molecule facilitate the second molecule binding (cooperativity)

P 50 (partial pressure of O2 at which Hb is half saturated with O2) 26.6mmHg

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14
Q

The normal position of curve depends on

A

Concentration of 2,3-DPG
H+ ion concentration (pH)
CO2 in red blood cells
Structure of Hb

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15
Q

what causes Right shift

A 
(easy oxygen delivery)
High 2,3-DPG
High H+
High CO2
HbS
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16
Q

what causes left shift

A

(give up oxygen less readily)
Low 2,3-DPG
HbF
Low H+

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17
Q

what is Hemoglobinopathy give examples

A

Genetic disorders characterized by a defect of globin chain synthesis:

Structural variants of haemoglobin
Defects in globin chain synthesis (thalassaemia)

Most common inherited single gene disorder worldwide

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18
Q

Classification of thalassaemia

A

Globin type affected

Clinical severity:
minor “trait”
intermedia
major

19
Q

what is Beta (b) thalassaemia, where is it prevalent

A

Deletion or mutation in b globin gene(s)
Reduced or absent production of b globin chains
Prevalence – mainly Mediterranean countries

20
Q

describe Inheritance of Beta thalassaemia, characteristics of carriers

A

Beta Thalassaemia is inherited in a recessive mendelian fashion.

(beta -o = no globing production, b+ = decreased globin production which gives rise to major/media

The Carriers are asymptomatic save for the microcytic hypochromic indices

21
Q

how can thalassaemia be diagnosed

A

FBC- Microcytic Hypochromic indices, Increased RBCs relative to Hb

THERE IS ABSENCE OF IRON DEFFICIENCY

Film- Target cells, poikilocytosis but no anisocytosis

High Performance Liquid Chromatography
(in beta thal. raised HbA2/HbF

Globin Chain synthesis/ DNA studies = only reliable

22
Q

what is the main feature of thalassaeimia

A

a microcytic hypochromic blood picture in the absence of iron deficiency.
RBC count is relatively high when compared to the haemoglobin.

23
Q

What is Thalassaemia Major

A

Carry 2 abnormal copies of the beta globin gene

Severe anaemia, incompatible with life without regular blood transfusions

Clinical presentation usually after 4-6 months of life

24
Q

Name an extra indicator of beta thal major on peripheral blood film

A

Often Howell Jolly bodies and nucleated RBC’s will be present as a result of splenectophy/hyper plastic bone

25
Q

RBC inclusions in b Thalassaemia

A

alpha chain precipitates

Pappenheimer Bodies (using Perls stain)

26
Q

Clinical presentation of Thalassaemia Major

A

Severe anaemia usually presenting after 4 months
Hepatosplenomegaly
Blood film shows gross hypochromia, poikilocytosis and many NRBCs
Bone marrow - erythroid hyperplasia
Extra-medullary haematopoiesis

27
Q

b Thalassaemia – clinical features

A 
Chronic fatigue
Failure to thrive
Jaundice
Delay in growth and puberty
Skeletal deformity
Splenomegaly
Iron overload
28
Q

Other complications of b thalassaemia

A

Cholelithiasis and biliary sepsis
Cardiac failure
Endocrinopathies
Liver failure

29
Q

what is most likely cause low death in b thal

A

Cardiac disease

less likely - infections > liver

30
Q

Thalassaemia Major- treatment

A 
Regular blood transfusions
Iron chelation therapy
Splenectomy
Supportive medical care
Hormone therapy
Hydroxyurea to boost HbF
Bone marrow transplant
31
Q

describe transfusion treatment

A

Phenotyped red cells
Aim for pre-transfusion Hb 95-100g/L
Regular transfusion 2-4 weekly
If high requirement, consider splenectomy

32
Q

common infections

A

Yersinia

Other Gram negative sepsis

33
Q

infection management

A

Prophylaxis in splenectomised patients – immunisation and antibiotics

34
Q

Name 2 iron chelators

A

Deferiprone

Deferasirox

35
Q

describe Deferasirox

A

Oral - specific and controls body iron well

SE: rash, GI symptoms, hepatitis, renal impairment

36
Q

describe Desferrioxamine

A

Sc infusion (or IV in cardiac iron overload)

SE: ocular/auditory/skeletal
vertebral dysplasia, pseudo-rickets, retinopathy, high tone sensorineural loss, increased risk of Yersinia infection
Parental = compliance issues

37
Q

describe Deferiprone

A

Oral
Effective in reducing myocardial iron
SE: GI disturbance, hepatic impairment, neutropenia, agranulocytosis, arthropathy

38
Q

Monitoring of iron overload

A

Serum ferritin
>2500 associated with significantly increased complications

Liver biopsy
T2* cardiac and hepatic MRI
Ferriscan – R2 MRI

39
Q

what is HbE Beta Thalassaemia

A

Very common combination in South East Asia

Clinically variable in expression can be as severe as thalassaemia major

40
Q

what is Alpha Thalassaemia

A

Deletion or mutation in a globin gene(s)
Reduced or absent production of a globin chains
Affects both foetus and adult

Excess beta and gamma chains form tetramers of HbH and Hb Barts respectively

41
Q

what is severity of alpha thal dependent on

A

Severity depends on number of  globin genes affected

42
Q

what is a thalassaemia carrier

A

Also known as Thalassaemia minor / trait
Carry a single abnormal copy of the beta globin gene
Usually asymptomatic
Mild anaemia

43
Q

Problems Associated with Treatment in Developing Countries

A

Lack of awareness/experience
Availability of blood
Cost and compliance with iron chelation therapy
Availability of bone marrow transplant

44
Q

Screening and Prevention

A

health education for thalassaemics, family members and general public
Extended family screening
Pre-marital screening/Discourage marriage between relatives?
Antenatal testing
Pre-natal diagnosis (CVS)

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