HAEMOGLOBINOPATHY CARRIERS
Genotype
Special
features
Additional
comments
Action
Required
Haemoglobin AA
Normal haemoglobin
None
Alpha (α+) Plus
Thalassaemia
Trait/carrier
DNA required to
confirm carrier state
(Genetic counselling
only if known risk of
interaction with alpha
zero thalassaemia)
Alpha (α0) Zero
Thalassaemia
Trait/Carrier
Beta (β)
Thalassaemia
Trait/Carrier
2 alpha (α) gene
deletion
Normal A2
Reduced MCV & MCH
DNA required to
confirm carrier state
Elevated A2
Reduced MCV & MCH
Reduced production
of ßeta globin chains
May be
misdiagnosed as iron
deficiency anaemia
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Silent carrier state
May resemble iron
deficiency anaemia
with normal iron
serum levels
Possible mild
anaemia
Unless iron deficient,
then no supplement
required
Severity of any
condition inherited
depends on the
genotype
Genetic counselling
DNA to confirm
diagnosis
Partner screening if
both are from a high
risk group
Genetic counselling
Sometimes requires
DNA to confirm
diagnosis
Partner screening
Not diagnosed in
newborn due to high
level of fetal
haemoglobin which
masks carrier state
Populations Most
Likely to be Carriers
(but not exclusively)
Normal haemoglobin seen
in all populations
Most common
haemoglobinopathy in
populations world-wide
Interaction
with
Condition as a
result of interaction
No interaction
Not applicable
Alpha zero
thalassaemia
Haemoglobin H
Disease (Hb H
Disease)
Not clinically significant
China (including Hong
Kong), Taiwan, Thailand,
Cambodia, Laos, Vietnam,
Indonesia, Burma,
Malaysia, Singapore,
Philippines, Cyprus,
Turkey, Greece, Sardinia,
unknown family origins
Alpha zero
thalassaemia
Offer couple PND if
“at risk”
Alpha thalassaemia
major (Hb Barts Hydrops
Fetalis)
Alpha plus
thalassaemia
Haemoglobin H
Disease (Hb H
Disease)
Mediterranean
Middle East
South East Asian
South Asian (China,
Indonesia, Vietnam and
other countries in the
region)
Caribbean
African
βeta thalassaemia
Offer couple PND if
“at risk”
βeta thalassaemia major
or
βeta thalassaemia
Intermedia*
Hb Lepore
Assessment by
Specialist - Offer
PND if indicated
May present as
Thalassaemia Major* or
Thalassaemia
Intermedia*
(Also White British
est. 1:1000)
Hb S
Offer PND if “at risk”
S βeta Thalassaemia
(S/β thalassaemia)
Hb E
Offer PND if “at risk”
E/β thalassaemia may
present as Thalassaemia
Major or Thalassaemia
Intermedia*
Delta beta (δβ)
thalassaemia
Assessment by
Specialist - Offer
PND if indicated
May present as
Thalassaemia Major* or
Thalassaemia
Intermedia*
O Arab
Assessment by
Specialist - Offer
PND if indicated
OArab /β Thalassaemia
usually similar to
Thalassaemia
Intermedia*
Genotype
Hb Lepore
(Hb A/Lepore)
Delta (δ) Beta (β)
thalassaemia
(Hb A/δβ
thalassaemia)
Hereditary
Persistence of Fetal
Haemoglobin
(Hb A/HPFH)
Haemoglobin E
Trait/Carrier
(Hb AE)
Haemoglobin DPunjab
Trait/Carrier
(Hb ADPunjab) Also
called DLos Angeles
Other Hb Ds are
usually not
significant
Haemoglobin C
Trait/Carrier
(Hb AC)
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Special
features
Borderline anaemia
Borderline anaemia
Microcytic
Hypochromic
Usually 2% of total
haemoglobin in
adults
Highest %
haemoglobin in
babies
Additional
comments
Occasional enlarged
spleen
Occasional enlarged
spleen
May be
misdiagnosed as iron
deficiency anaemia
Can be increased
during pregnancy,
also sometimes
increased in patients
with sickle cell
anaemia
Lysine substituted
for glutamic acid,
26th point ß globin
chain
Possible
Hypochromic
Microcytic
Glutamine
substituted for
glutamic acid, 121
point, ß globin chain
Important to identify
DPunjab from other Hb
Ds due to clinical
interaction with Hb S
Lysine substituted
for glutamic acid, 6th
point, ß globin chain
Action
Required
Genetic counselling
Partner screening
Genetic counselling
Partner screening
Important to
distinguish Hb SS from
Hb S/HPFH and S/β
thalassaemia in
newborn screening
Genetic counselling
Partner screening
Genetic counselling
Partner screening
Genetic Counselling
Partner screening
Populations Most
Likely to be Carriers
(but not exclusively)
Mediterranean (Greek,
Italian)
Mediterranean (Greek,
Italian)
Africans
Caribbean
Interaction
with
Condition as a
result of interaction
βeta thalassaemia
Assessment by
Specialist - Offer
PND if indicated
May present as
Thalassaemia Major* or
Thalassaemia
Intermedia*
Sickle cell (Hb AS)
Assessment by
Specialist - Offer
PND if indicated
Hb S/Lepore has variable
clinical severity
βeta thalassaemia
Assessment by
Specialist - Offer
PND if indicated
May present as
Thalassaemia Major* or
Thalassaemia
Intermedia*
Sickle cell (Hb AS)
Assessment by
Specialist
Hb S/δβ thalassaemia
Sickle cell (Hb AS)
Assessment by
Specialist
PND is not
indicated
S/HPFH
Does not usually require
treatment
βeta thalassaemia
Assessment by
Specialist - Offer
PND if indicated
E/β thalassaemia may
present as Thalassaemia
Major or Thalassaemia
Intermedia*
Sickle cell (Hb AS)
Assessment by
Specialist
Hb S/E Disease
Usually a very mild sickle
cell condition
Indian
Pakistan
Caribbean
(Also White British)
Sickle haemoglobin
(Hb S)
Offer PND if couple
“at risk” of having a
child with this
condition
Hb S/DPunjab
West African
Caribbean
Sickle haemoglobin
(Hb S)
Offer PND if couple
“at risk” of having a
child with this
condition
Hb S/C Disorder
South East Asia (India,
Bangladesh)
South Asia (China,
Vietnam, Thailand,
Indonesia and other
countries in the region)
Caribbean
Special
features
Genotype
Hb OArab (Hb AOArab)
Trait/Carrier
Also known as Hb
Egypt
Sickle Cell
Trait/Carrier
(Hb AS)
Additional
comments
Action
Required
Populations Most
Likely to be Carriers
(but not exclusively)
Interaction
with
βeta thalassaemia
Lysine substituted
for glutamine at
121st point of the ß
globin chain
May have
intravascular sickling
if oxygen tension
excessively low (e.g.
during anaesthetic)
Genetic counselling
Partner screening
Possible haematuria
Possible increased
risk of urinary
infections in
pregnancy
Genetic counselling
Partner screening
North Africa
Saudi Arabia
Bulgaria/Eastern Europe
Eastern Mediterranean
African
Caribbean
South East Asians
Mediterranean
Assessment by
Specialist
Sickle haemoglobin
(Hb S)
Condition as a
result of interaction
OArab/ β thalassaemia
Assessment by
Specialist - Offer PND if
indicated
S/OArab
βeta thalassaemia
Offer PND if “at risk”
S/βeta Thalassaemia
(S/β thalassaemia)
Hb C
Offer PND if “at risk”
Hb S/C Disease
Hb S
Offer PND if “at risk”
Sickle Cell Anaemia
(Hb SS)
Hb DPunjab
Offer PND if “at risk”
Hb S/DPunjab
Hb O (Arab)
Offer PND if “at risk”
Hb S/OArab
Delta beta (δβ)
Thalassaemia
Hb S/δβ thalassaemia
Assessment by
Specialist
Hb Lepore
thalassaemia
Assessment by
Specialist
HPFH
Serious Interaction
Less Serious Interaction
Hb S/Lepore
thalassaemia
S/Hereditary Persistence
Fetal Haemoglobin
(S/HPFH)
Minimal clinical significance
References
Bain BJ (2006) Other significant haemoglobinopathies. Haemoglobinopathy Diagnosis, 2nd Edition Blackwall Publishing Ltd
Brent Sickle Cell & Thalassaemia Centre (2010) Interpreting Common Haemoglobinopathy Test Results – A Guide for Primary Health Care Professionals. http://sicklethal.nwlh.nhs.uk/
NHS Sickle Cell & Thalassaemia Screening Programme (2012) Handbook for Laboratories. 3rd Edition.
https://www.gov.uk/government/publications/sickle-cell-and-thalassaemia-screening-handbook-for-laboratories
Ryan et al on behalf of the British Committee for Standards in Haematology (2010) Significant haemoglobinopathies: guidelines for screening and diagnosis. Blackwall
Publishing Ltd British Journal of Haematology149, 35-49 http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2009.08054.x/epdf
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