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Haematology > Haemoglobinopathy > Flashcards

Haemoglobinopathy Flashcards

1
Q

what is the role of the globin chains

A

keep haem soluble and protect it from oxidation

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2
Q

what are the major forms of haemoglobin

A

HbA- 2 alpha and 2 beta (97% of Hb in adults)
HbA2- 2 alpha and 2 delta (important in beta thalassemia, 2.5% in adults )
HbF- 2 alpha and 2 gamma (fetal, 0-0.5% in adults)

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3
Q

what genes control the globin chain production

A

alpha chromosome 16

beta chromosome 11

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4
Q

when does Hb become adult

A

reached by 6-12 months of age (beta chains wont manifest till then)

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5
Q

what happen around birth to haemoglobin

A

increasing beta globin production and dropping gamma production

implications of this mean at birth wont know if problem with beta chain production as still have some gamma synthesis

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6
Q

what are haemoglobinopathies

A

hereditary conditions affecting globin chain synthesis

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7
Q

what is the inheritance of haemoglobinopathies

A

behave as autosomal recessive disorders

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8
Q

what are the two main groups of haemoglobinopathies

A

thalassaemias= decreased rate of globin chain synthesis = impaired Hb production

structural haemoglobin variants= normal production of abnormal globin chain creating variant haemoglobins (e.g. HbS- sickle cells)

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9
Q

what are the types of thalassaemias

A 
alpha= affects alpha chains 
beta= affects beta chains
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10
Q

what are the consequences of thalassaemias

A

inadequate Hb production = microcytic hypochromic anaemia

if severe:
-unbalanced accumulation of globin chains (dysfunctional globin toxic to the cell)
-haemolysis
-ineffective erythropoiesis = severe anaemia
=jaundice (due to increased apoptosis and haemolysis)

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11
Q

what is the commonest monogenic disorder

A

haemoglobinopathies- big cause of mortality worldwide

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12
Q

where is thalassaemia common

A

in areas of malaria endemic - has driven these mutations as carrier states for thalassaemia makes you less likely to contract malaria

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13
Q

what is the genetics behinds alpha thalasaemia

A

mutations affecting globin chain synthesis
(unaffected have four normal alpha genes- 2 fro each parent)
affected will have deletion of one or both alpha genes resulting in reduced or absent synthesis from that chromosome which affects alpha chain in AHb, HbA2, HbF

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14
Q

how do you classify the types alpha thalassaemias

A

based on number of alpha genes
alpha thalassaemia trait= one/ two alpha chains missing
HbH disease= only one alpha gene left
Hb barts hydroos fetalis= no functional alpha genes (not compatible with life)

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15
Q

what are the features of alpha thalassaemia trait

A

asymptomatic carrier state, no Tx needed
microcytic hypochromic red cells with milkd anaemia

(important to distinguish from iron deficiency- ferritin will be normal here)

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16
Q

what is HbH disease

A

more severe form of alpha thalassaemia where only one working alpha gene per cell

17
Q

what are the clinical features of HbH disease

A

anaemia with very low MCV and MCH (mean corpuscular Hb)

(the more genes you loose the smaller then rbcs are going to be)

jaundice, splenomegaly, may need transfusion

(jaundice because of ineffective erythropoiesis and chronic haemolysis)

common in SE asia

18
Q

what must happen for HbH disease to be inherited

A

both parents must be alpha thalassaemia carriers (AR inheritance)
(need to get 3/4 alpha genes affected- one parent will have 2 affected, one will have 1)

19
Q

what are the features of beta thalassaemia major

A

severe, lifelong transfusion dependency

presents aged 6-24 months as HbF falls with pallor and failure to thrive

extramedullary haematopoiesis causes: hepatosplenomegaly (extramedullary haematopoiesis), skeletal changes (expansion of bone marrow to try and make rbcs), organ damage

20
Q

what is the treatment for beta thalassaemia major

A 
transfusion lifelong
want to maintain Hb at 95-105 as this:
Suppresses ineffective erythropoiesis
Inhibits over-absorption of iron
allows normal growth and development

bone marrow transplant an option before comps develops (curative)

21
Q

what is the major cause of death in beta thalassaemia major

A

iron overload from transfusion
(With a severe anaemia; body will try to increase iron absorption to increase Hb production resulting in iron overload as there is no globin for the haem to bind to)

22
Q

what are the consequences of iron overload

A

endocrine dysfunction (impaired growth and pubertal development, diabetes, osteoporosis)

cardiac disease (cardiomyopathy, arrhythmias)

liver disease (cirrhosis, hepatocellular cancer)

23
Q

what does a rb cell look like in sickle disorders

A

distorted, not biconcave disc

24
Q

what can precipitate a sickle crisis

A 
hypoxia
dehydration 
infection 
cold exposure 
stress/ fatigue

(can happen with no obvious trigger)

25
Q

what is the long term management for sickling disorders

A

MOST IMPORTANT:
as hyposplenism need to reduce risk of infections
-prophylactic penicillin
-vaccination: pneumocccus, meningococcus, haemophilus

folic acid supplementation (increase rbc turnover so increased demand) (as for any chronic anaemia)

hydroxycarbamide (induces HbF production, reduces disease severity)

regular transfusion to prevent stroke in some cases

26
Q

how are haemoglobinopathies diagnosed

A

FBC
Hb
red cell indices
blood film (helpful for sickle cell and HbH- alpha thal disease)
(are the micro or macro, are the hypochromic)

27
Q

how are haemoglobinopathies diagnosed

A

FBC
Hb
red cell indices
blood film (helpful for sickle cell and HbH- alpha thal disease)
(are the micro or macro, are the hypochromic)

ethnicity important

HPLC or electrophoresis to quantify Hb:
RAISED HbA2 DIAGNOSTIC OF BETA THAL TRAIT
identifies abnormal Hb e.g. HbS

28
Q

what are Hb analysis like in a normal patient

A

HbA >80%
HbF >1%
HbA2 1.5-3.5%

29
Q

what will Hb and MCV be like in sickle cell trait

A

MCV normal

Hb normal value but HbS

30
Q

what should you suspect in microcytic hypochromic anaemia with normal ferritin

A

thalassaemias

31
Q

how is beta thal trait diagnosed

A

raised HbA2

32
Q

what screening is done for haemoglobinopathies

A

antenatal screening to identify carrier parents
family origin questionaire and FBC
further testing is high risk area/ abnormal RBC indices

counselling
prenatal diagnosis offered

newborn screening

Haematology (27 decks)

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