haemoglobinopathies Flashcards
what shape are RBC
biconcave
what shape are RBC
biconcave
do RBC have nuclei
no
what is the function of RBC
transport oxygen which is found to haemoglobin
what molecule controls RBC levels and where is this molecule synthesised
Erythropoetein (EPO)
Kidney.
are the globin chains covalently bonded in haemoglobin
No.
what is the composition of haemoglobin in terms of the alpha and beta chains
2 alpha chains
2 beta chains
what is the function of glob in
protect harm from oxidation
renders the molecule soluble.
what is the composition of feral haemoglobin in terms of the alpha and gamma chains
2 alpha and 2 gamma chains
which 2 chromosomes control the glob in chains
chromosome 16- alpha
chromosome 11- gamma, delta and beta.
where is haemoglobin produced
3 places from inter to at birth
in the yolk sac -in utero
liver or spleen -10-12 weeks development in utero
bone marrow- end of gestation
define haemoglobinopathies
changes in globin genes or their expression leads to disease.
2 main types of haemoglobinpathies
structural-sickle cell (base substitution)
Thalassaemia- change in globin gene expression leads to reduced rate of synthesis of NORMAL globin chains.
plasma volume expands by how much in pregnancy
50%
red cell mass expands by how much in pregnancy
25%
what is defined as anaemia in the 1st and 3rd trimester
what is defined as anaemia in the second trimester
what happens to the number of white blood cells in pregnancy
Leukocytosis- increase in WBC
what happens to the platelet count during pregnancy
thrombocytopenia
platelet count is low- below the normal level but this is a physiological process.
causes of thrombocyopenia in pregnancy
production failure- severe folate deficiency.
Consumptive- gestational, pre-eclampsia and HELLP syndrome, AFLP, DIC e.g. in abruption TTP/HUS.
what makes pregnancy a prothrombotic state
platelet activation increase in procoagulant factors reduction in natural anticoagulants. reduction in fibrinolysis rise in markers of thrombin generation coagulation factors
how are haemoglobinopathies diagnosed/ detected.
Electrophoresis- for structural abnormalities.
Isoelectric focusing
High performance liquid chromatography.
Oxygen dissociation curve (p50, high affinity)
DNA analysis (genetic counseling, prenatal Dx)
Mass spectrometry
Kleihauer testing, Supravital staining, Sickle solubility
what is the substation which occurs in sickle cell anaemia
valine substituted for glutamine at postion 6 on B globin chain
why is the presentation of sickle cell only present 6 months after birth
foetal haemoglobin is present until 6 months after birth.
when do symptoms of sickle cell anaemia become evident
when extreme hypoxia/dehydration (eg very bad anaesthetia, flying unpressurised military aircraft)
acute complications of sickle cell disease.
Vaso-occlusicve crisis- hands and feet (dactylitis), chest syndrome, abdominal pain (mesenteric), bones (long bones, ribs, sin, brain, priapism-painful erection).
Septicaemia.
Aplastic crisis.
Sequestration crisis (spleen, liver).
chronic complications of sickle cell anaemia
Hyposplenism - due to infarction and atrophy of spleen, increased risk of infection.
Renal disease: medullary infarction with papillary necrosis. Tubular damage - can’t concentrate urine (bed-wetting at night). Glomerular – chronic renal failure/dialysis
Avascular necrosis (AVN) –femoral/humeral heads- need replacement, life long peniciclin.
Leg ulcers, osteomyelitis, gall stones, retinopathy, cardiac, respiratory
treatment for sickle cell anaemia.
Penicillin etc from 6 months
treatment for vaso-oclussion in sickle cell anaemia
analgesia (usually opiates), hydration (to maintain red cell water)
why is blood transfused in sickle cell anaemia.
Top up: splenic sequestration, aplastic crisis, pre-operative, acute chest crisis (usually when Hb
what is the function of Hydroxycarbamide
Increases Hb F
how do you cure sickle cell anaemia
Bone Marrow Transplant from normal donor
how can sickle cell be prevented
genetic counselling/prenatal diagnosis, avoiding precipitants
how many forms of thalasemia are there
4
α, β, δβ and γδβ
what is Hb harts
consists of four gamma chains. It is moderately insoluble, and therefore accumulates in the red blood cells
why is little oxygen delivered to tissues when you have Hb harts
It has an extremely high affinity for oxygen,
HbA thalassemia is more severe than B
foetal haemoglobin requires alpha but not b chains.
do RBC have nuclei
no
what is the function of RBC
transport oxygen which is found to haemoglobin
what molecule controls RBC levels and where is this molecule synthesised
Erythropoetein (EPO)
Kidney.
are the globin chains covalently bonded in haemoglobin
No.
what is the composition of haemoglobin in terms of the alpha and beta chains
2 alpha chains
2 beta chains
what is the function of glob in
protect harm from oxidation
renders the molecule soluble.
what is the composition of feral haemoglobin in terms of the alpha and gamma chains
2 alpha and 2 gamma chains
which 2 chromosomes control the glob in chains
chromosome 16- alpha
chromosome 11- gamma, delta and beta.
where is haemoglobin produced
3 places from inter to at birth
in the yolk sac -in utero
liver or spleen -10-12 weeks development in utero
bone marrow- end of gestation
define haemoglobinopathies
changes in globin genes or their expression leads to disease.
2 main types of haemoglobinpathies
structural-sickle cell (base substitution)
Thalassaemia- change in globin gene expression leads to reduced rate of synthesis of NORMAL globin chains.
plasma volume expands by how much in pregnancy
50%
red cell mass expands by how much in pregnancy
25%
what is defined as anaemia in the 1st and 3rd trimester
what is defined as anaemia in the second trimester
Endocrine complications of iron chelation.
Growth and development, screening for glucose intolerance, hypothyroidism and hypoparathyroidism.
liver complications of iron chelation
LFT, ferritin, Hep Serology, MRI. Hepatologist if established disease
causes of thrombocyopenia in pregnancy
production failure- severe folate deficiency.
Consumptive- gestational, pre-eclampsia and HELLP syndrome, AFLP, DIC e.g. in abruption TTP/HUS.
what makes pregnancy a prothrombotic state
platelet activation increase in procoagulant factors reduction in natural anticoagulants. reduction in fibrinolysis rise in markers of thrombin generation coagulation factors
how are haemoglobinopathies diagnosed/ detected.
Electrophoresis- for structural abnormalities.
Isoelectric focusing
High performance liquid chromatography.
Oxygen dissociation curve (p50, high affinity)
DNA analysis (genetic counseling, prenatal Dx)
Mass spectrometry
Kleihauer testing, Supravital staining, Sickle solubility
what is the substation which occurs in sickle cell anaemia
valine substituted for glutamine at postion 6 on B globin chain
why is the presentation of sickle cell only present 6 months after birth
foetal haemoglobin is present until 6 months after birth.
when do symptoms of sickle cell anaemia become evident
when extreme hypoxia/dehydration (eg very bad anaesthetia, flying unpressurised military aircraft)
acute complications of sickle cell disease.
Vaso-occlusicve crisis- hands and feet (dactylitis), chest syndrome, abdominal pain (mesenteric), bones (long bones, ribs, sin, brain, priapism-painful erection).
Septicaemia.
Aplastic crisis.
Sequestration crisis (spleen, liver).
chronic complications of sickle cell anaemia
Hyposplenism - due to infarction and atrophy of spleen, increased risk of infection.
Renal disease: medullary infarction with papillary necrosis. Tubular damage - can’t concentrate urine (bed-wetting at night). Glomerular – chronic renal failure/dialysis
Avascular necrosis (AVN) –femoral/humeral heads- need replacement, life long peniciclin.
Leg ulcers, osteomyelitis, gall stones, retinopathy, cardiac, respiratory
treatment for sickle cell anaemia.
Penicillin etc from 6 months
treatment for vaso-oclussion in sickle cell anaemia
analgesia (usually opiates), hydration (to maintain red cell water)
why is blood transfused in sickle cell anaemia.
Top up: splenic sequestration, aplastic crisis, pre-operative, acute chest crisis (usually when Hb
what is the function of Hydroxycarbamide
Increases Hb F
how do you cure sickle cell anaemia
Bone Marrow Transplant from normal donor
how can sickle cell be prevented
genetic counselling/prenatal diagnosis, avoiding precipitants
how many forms of thalasemia are there
4
α, β, δβ and γδβ
what is Hb harts
consists of four gamma chains. It is moderately insoluble, and therefore accumulates in the red blood cells
why is little oxygen delivered to tissues when you have Hb harts
It has an extremely high affinity for oxygen,
HbA thalassemia is more severe than B
foetal haemoglobin requires alpha but not b chains.
blood film b thalassaemia
abnormal with lots of nucleated red cells.
clinical features of thalassaemia
severe anaemia
death from infection
Short stature and distorted limb growth due to premature closure of epiphyses in long bonesEnlarged liver and spleen “extramedullary haemopoiesis”
thalassemia facies include
o Maxillary hypertrophy
o Abnormal dentition
o Frontal bossing due to expanded bone marrow
pathology of B thalassemia
Increased marrow activity- skeletal deformities and stunted growth, increased iron absorption and organ damage (exacerbated by blood transfusion, Protein malnutrition.
Enlarged and overactive spleen- pooling of RBC and increased trans fusion requirement.
classic X ray seen due to bone marrow expansion in thalassemia.
• X-ray showing classical “hair on end” skull due to widening of diploic cavities by marrow expansion
trearment for B thlassemia.
- Tranfusion- to maintain mean hb 12 g/dl (pre-transfusion Hb 9.5-10)
- Suppresses marrow red cell production and prevents skeletal deformity and liver/spleen enlargement
how often are transfusions for the first year of B thalassemia
3-4 weeks
complications of transfusions in thalassemia include
iron overload
each unit of red cells contains 200-250mg Iron and the body has
no excretory mechanism for iron, therefore iron has to be removed
complications of iron overload due to transfusion
gonads/hypothalamus – failure of puberty, growth failure
pancreas – diabetes
heart – dilated cardiomyopathy and heart failure
liver – cirrhosis.
major complications of blood transfusion
Transmission of infection
Allo-immunisation- immune response to foreign antigens after exposure to genetically different cells or tissues
Causes of death in thalassaemia
Most common is heart failure
Infection
Arrhythmias
solution to prevent iron overload from transfusion
chelation therapy
iron chelators include
Desferrioxamine
Deferiprone and Deferasirox
what is the target ferrite level to aim for with iron chelators and why is the peel still higher than normal
1000-1500µg/L
If tried to reduce iron levels further would result in toxicity from iron chelators.
Monitoring chelation
Ferritin (acute phase), liver biopsy, MRI (T2*)
prevention of haemoglobinopathies
genetic counselling
anatenatal screening
neonatal screening
gene therapy
Endocrine complications of blood transfusion.
Growth and development, screening for glucose intolerance, hypothyroidism and hypoparathyroidism.
liver complications of blood transfusion
LFT, ferritin, Hep Serology, MRI. Hepatologist if established disease
why does transfusion increase risk of infections
decreased CD4/8 ratio and defective neutrophil chemotaxis, increased virulence with excess iron (yersinia and DFO), line infections, transfusion transmitted infection.
Or
directly from donor blood
