Haemoglobinopathy overview Flashcards
Describe the structure of Hb?
Tetramer, made up of 2 alpha globin like chains and 2 beta globin like chains
ONE hame group attached to EACH globin chain
Name the major forms haemoglobin and their structure?
-which form is present in adults greatest quantities?
-HbA (2 alpha chains and 2 beta chains) HbA2 (2 alpha chains and 2 delta chains) HbF (foetal) (2 alpha chains and 2 gamma chains)
-HbA
What chromosomes are involved in alpha and beta globulin chain production?
Alpha like genes on chromosome 16
2 alpha genes per chromosome (4 per cell)
Beta like genes are on chromosome 11
1 beta gene per chromsome (2 per cell)
What are haemoglobinopathies?
- inheritance?
- what are the 2 main groups?
hereditary conditions affecting globin chain synthesis
- usually autosomal recessive
- Thalassaemias and structural Hb variants
-What are structural Hb variants?
-normal production of structurally abnormal globin chain = variants Hb e.g. HbS
Thalassaemias
- definition?
- what type of anaemia does this cause?
- what happens to the resulting RBCs?
- where are thalassaemias most prevalent
- hereditary disorders of globin chain synthesis resulting in impaired Hb production
- inadequate Hb production = Microcytic, hypochromic anaemia
- there is ineffective erythropoiesis and so haemolysis occurs
- malaria endemic areas
Alpha thalassaemia
- mutation affects what?
- underlying mutation?
- Hb affected?
- classification? (3)
- alpha globin chain synthesis i.e. giving reduced/absent alpha chain synthesis
- deletion of 1 or both alpha genes from chromosome 16
- HbA, HbA2, HbF all affected
-Alpha thalassaemia trait (one or two genes missing) HbH disease (only one alpha been left Hb Barts Hydrops fetalis (no functional genes)
Alpha thalassaemia trait
- presentation?
- lab results?
- mistaken for what?
- asymptomatic, no treatment needed
- Microcytic, hypo chromic red cells with MILD anaemia
- iron def
HbH disease
- how many genes per cell?
- lab results?
- what is HbH?
- what can be seen on blood film?
- clinical features & why? (5)
- one
- anaemia + very low MCV and MCH
- excess Beta chains form tetramers called HbH which cannot carry oxygen
- HbH bodies
-Anaemia
Splenomegaly (extra medullary haematopoiesis)
Jaundice (haemolysis and ineffective erythropoiesis)
commonest in S.E. Asian/middle east/ Med patients
Hb Bart’s hydrops fetalis syndrome
- no. genes in cell?
- consequence?
- clinical features? (6)
-none
-minimal or no alpha chain production i.e. HbA not made
Hb Barts and HbH are then the majority of Hb at birth
-severe anaemia cardiac failure, oedema growth retardation severe hepatosplenomegaly skeletal and CV abnormalities Most die in utero
Beta thalassaemia
- what is it?
- what Hb is affected?
- caused by what form of mutation?
- classification & features? (3)
- disorder of beta chain synthesis
- only HbA
- point mutations
-B thalassaemia trait (asymptomatic, low MCV/MCH) Beta thalassaeia intermedia (moderate severity requiring occasional transfusion) Beta thalassaemia major (no Beta chains produced, severe)
Beta thalassaemia major
- what is seen on lab tests?
- blood film?
- type of Hb mostly present?
- clinical features? (6)
- management?
- main complication of ^?
- other complications? (4)
-severe anaemia
reticulocytosis, very low MCV/MCH
- microcytosis, hypochromia, anisopoikilocytosis and target cells
- HbF
-present ages 6-24 moths failure to thrive pallor haepatosplenomegaly skeletal changes organ damage
-regular transfusion programme to maintain Hua t 95-105g/l
this will suppress ineffective erythropoiesis and inhibit over absorption of iron
BM transplant before complications develop
-Iron overload
-viral infection- HIV, Hep B and C
alloantibodies- hard to cross match
transfusion reactions
increased risk of bacterial sepsis
What are the consequences of iron overload?
- endocrine (3)?
- cardiac (2)?
- liver (2)?
- management?
-impaired growth and pubertal development
-cardiomyopathy
arrhythmias
-cirrhosis
hepatocellular cancer
-can’t of venesection as already anaemic
use Iron chelating drugs e.g. Desferrioxamine
(these for an Fe/chelator complex and excess iron excreted in stool)
Diagnosis of thalassameia
- exclude?
- what is seen on blood film generally?
- investigation?
- iron def
- hypochromia, target cells, anisopoikilocytosis
-high performance liquid chromatography
this quantifies presence of HbA, HbA2 and HbF
identifies abnormal Hb
Describe the pathophysiology of sickling disorders:
- type of mutation and location?
- consequences of mutation?
-point mutation in codon 6 of the Beta globin gene that substitutes Glutamine to valine
-alters structure of Hb to form HbS
HbS polymerises if exposed to low O2 levels ad this distorts the red cell damaging the membrane
Sickle trait
- how many abnormal genes?
- presentation?
- blood film?
- main Hb present?
- one abnormal gene
- asymptomatic carrier (may sickle in extreme hypoxia)
- normal
- Mainly HbA, HbS < 50%
Sickle cell anaemia (HbSS)
- no. of abnormal genes?
- main Hb present?
- presentation? (3)
- precipitants of a crisis? (6)
- treatment of painful crisis?
- long term effects? (3)
- long term treatment? (3)
- 2 abnormal genes
- HbS > 80%, no HbA
-Sickle crisis (episodes of tissue infarction due to vascular occlusion can occur anywhere, pain may be severe) Chronic haemolysis (shortened RBC life span Hyposplenism (repeated splenic infarcts)
-hypoxia, dehydration, infection, cold, stress/fatigue
-opiate analgesia hydration rest Oxygen antibiotics if infection severe= red cell exchange transfusion (venesection + transfusion)
-impaired growth
risk of sepsis
risk of organ damage
(pulmonary hypertension, renal disease, avascular necrosis, leg ulcers, stroke)
-hyposplenism requires prophylactic penicillin, vaccination against pneumococcus, meningococcus, haemophilus
folic acid supplements
hydroxycarbamide to induce HbF production
name another type of sickling disease?
compound heterozygosity for HbS and another Beta chain mutation
e.g. HbS/Beta thal
HbSC
screening for Haemoglobinopathies
-how is this done?
Antenatal screening to identify carrier parents now standard
family origin questionnaire and FBC
further testing of from high risk area or abnormal RBS indices
