HEMOGLOBINOPATHIES Flashcards
What are diff. forms of Hb? How diff. are they ?
- HbA (2 alpha and 2 beta chains)
- HbA2 (2 alpha and 2 delta)
- HbF (2 alpha and 2 gamma)
Wich is the major Hb in adults?
- HbA (2 alpha and 2 beta chains)
- –only 2% of HbA2
What is the signifcance of globin chains?
- KEEPS HAEM soluble and protect heme from oxidation
How are diff. forms of Hb formed? -
- Genetic control
- alpha like genes on Chromosome 16 (2 alpha genes per CHROMOSOME)
How does the globin chain prodn change over the years?
WHy is this significant?
- Beta Hb chain prodn RAMPS up by 6-12 months of age
- —gamma globin chain prodn is reduced at this time
- –Beta-thalassaemia only presents at 6-12 months
What are hemoglobinopathies?
hereditary conditions affecting the GLOBIN chain synthesis
—autosomal RECESSIVE d.o
What are the 2 main gr. of hemoglobinopathies?
- THALASSAEMIAS (DECR. rate of NORMAL globin chain synthesis)
- Structural Hb variants (mutation in the structural prodn of the Hb)
Give an example of structural Hb variant hemoglobinopathies?
-SICKLE cell anaemia
What is affected in Alpha thalassaemia?
Alpha chains are affected
What is a consequence of thalassaemias?
- INADEQUATE Hb prodn–> MICROCYTIC HYPOCHROMIC anaemia
- If severe (UNBALANCE accumulation of GLOBIN chains):
- hemolysis > JAUNDICE
- ineffective erythropoiesis
Describe the geographical distribution of Thalassaemia.
- MALARIA endemic areas has allowed the MUTATIONs to cherish
(central and east africa; ASIA, peri-meditarre.)
What occurs with ALPHA THALASSEMIA?
—–thalassaemia occurs with deletion of ONE or BOTH alpha genes from chromosome 16
What occurs with ONE working alpha gene out of 4?
- HbH disease
If NO working genes are left? -
Hb Barts Hydrops Fetalis
When does someone have thalassaemia trait?
How does the Alpha Thalassaemia trait present as?
if they only ONE or 2 alpha genes missing
———MILD anaemia
(microcytic, hypochromic red cell)—-but normal Hb levels
How to differentiate from iron def. (thalassaemia trait) ?
- FERRITIN is normal
What occurs pathophysiologically with alpha-thalassaemia?
- beta chains wnats to bind to something
- —they start to STICK to each other, forming TETRAMERS (HbH)—-red cell inclusions are seen of HbH
What is seen with HbH disease?
- ANAEMIA with v.LOW MCV and MCH
- Jaundice
- splenomegaly
What is seen on blood film of Hb Barts Hydrops Fetalis?
- no Hb
- NUMEROUS nucleated red cells
What is seen in Hydrops fetalis?
Profound anaemia Cardiac failure Growth retardation Severe hepatosplenomegaly Skeletal and cardiovascular abnormalities Almost all die in utero
Who presents with Beta thalassaemia major?
Bbies 6-24 months of age
How does Beta thalassaemia Major present as?
- skeletal damage
- organ damage
- hepatosplenomegaly
- —-PALLOR and FAILURE to thrive
—-all as a result of extramdeullary haematopoiesis
How to manage Beta Thal Maj?
- regular transfusion programme (supresses ineffective erythropoiesis)
- –allows NORMAL growth and develop.
What may occur with freq. transfusions?
How to prevent over-absorption of iron ?
- IRON overload —-main cause of mortality
—-maintain Hb at 95-105g/l
What endocrine dysfxns may result from iron overload?
- DIABETES
- HYPOTHYROIDISM
- OSTEOPOROSIS
- impaired growth and pubertal development
What cardiac condition may develop with IRON overload?
arrhythmias
- cardiomyopathy
- pericarditis
Can liver disease occur with iron overload?
yes
—–CIRRHOSIS and HCC
What genetic change is seen with Hb in sickle cell anaemia?
- point MUTATION codon 6 of globin gene, changing glutamine to valine> Beta-S globin prodn
—2 alphas and 2 beta-S = HbS
What is bad about Hbs?
Can polymerise when exposed to LOW oxygen levels for a prolonged period of time
—–distorting the red cell and damaging the membrane
When may a carrier of the sickle cell trait become symptomatic ?
- SEVERE hypoxia seen under anaesthesia and at HIGH altitudes
- –HbS <50%; normal blood film
What vascular problems may arise with sickle cell anaemia?
- EPISODE OF TISSUE infarction d.t vascular occlussion (sx depend on SITE and severity; pain is SEVERE)
- —chronic hemolysis
- —-REPEATED SPENIC INFARCTS > HYPOSPLENISM
How to manage sickle cell anaemia?-
- prophylactic penicillin, vaccinations (d.t hyposplenism; risk of infection)
- folic acid supplement (incr. rbc turnover)
- hydroxycarbamide (reduces severity of diseaseby inducing HbF prodn)
- regular transfusion to prevent stroke
What ivx are done with hemoglobinopathies?
FBC, Hb, Red cell indices
Blood film
ethnic origin
—–perform HPLC /electrophoresis (to quantify Hb present)
In what types of Hb do alpha globin chains exist in?
In which condition may these types be affected?
HbA
HbA2
HbF
Alpha-thalassaemia
Would HbH Disease patient need transfusion?
YES
—-d.t eventual jaundice and splenomegaly
Name the most severe form of Alpha thalassaemia.
Why is it severe?
- Hb Barts Hydrops Fetalis Syndrome
- -as NO alpha genes are inherited from either parents> minimal or NO alpha chain prodn (HbF and HbA can’t be made)
What is considered as a high risk of a Hb Barts Fetalis Syndrome?
- if BOTH prents are from SE asia
Anything done to avoid risk of Hydrops Foetalis?
- antenatal screening may help!
Which Hb type is affected in Beta thalassaemia?
HbA
2 ALPHA chains and 2 beta chains
How does the beta thalassaemia trait present as?
raised HbA2 (is diagnostic)
- asymptomatic
- no/mild anaemia
- low MCV/MCH
Which beta thalassaemia types requires blood transfusion?
Beta- thalassaemia Intermedia
Beta- thalassaemia Major (lifelong)
What is seen on Hb analysis of beta-thalassaemia Major?
- No HbA
- Mainly HbF
What are physical signs of extramedullary hematopoiesis?
- frontal bossing
- spinal cord compression
- spikey appearance of skull on xray
How severe is iron overload, IIary to transfusions?
- VERY
- similar to hemachromatosis (but early onset and worse)
- -BONE marrow transplant may be an OPTION !
Why does iron overload occur with blood transfusion?
- because there is 250mg of IRON per unit of RED cells
- —-chronic anaemia DRIVES incr. iron absorption
How to manage IRON overload?
- can’t do venesection (already anaemic)
- —> IRON chelating drugs (Desferrioxamine) ! —-enhances iron excretion
Name the diff. iron chelating agents.
- Desferrioxamine (IV/s.c); can cause ocular/ ototoxicity at HIGH doses
- Deferipone (Oral)
- -> better at removing CARDIAC iron
What are the S.E of deferipone?
- -> 1% agranulocytosis
- —arthralgia
- —-GI upset
Why are transfusion pts predisposed to SEPSIS?
- d.t excessive iron store
- —bacteria LOVES iron
List other complications of transfusion.
- Viral infection
- Alloantibodies
- Transfusion Rxns
What occurs genetically in Sickle Cell Anaemia?
- 2 abnormal beta genes
- —-HbS >80% (no HbA)
What is meant by sickle crisis?
- seen in HbSS pts
- —the sickle cells begin to OCCLUDE the small vessels, d.t the loss of the biconcave rbc shape > tissue infarctions
What makes sickle crisis worse?
- Hypoxia
- Dehydration
- INfection
- Cold exposure
- stress/ fatigue
How to treat acute sickle crisis?
- opiate analgesia
- hydration
- oxygen
- rest
- ANTIBIOTICS (evidence of infection)
- –red cell exchange transfusion —-if isckle crisis in brain/ lung
What is the Long-term management for Sickle cell?
- Prophylactic Pencillin d.t Hyposplenism
- Folic acid supplments (incr. in RBC turnover)
- Hydrocycarbamide (induces HbF prodn)
- regular transfusion
D.t Hyposplenism, what other vaccinations are done?
pneumococcus, meningococcu and hemophilus
Best way to dx SICKLE CELL ANAEMIA?
HPLC
- Hb High performance liquid chromatography
