Theme 7 Haematology: Haemaglobinopathies, Obstetric Haematology and paediatric haematology Flashcards
When do you have a haemoglobinopathy screening in pregnancy?
around 8 weeks
What testing is carried out if:
- In low prevalence area
- In high prevalence area
- family origin and FBC
2. HPLC +/- partner testing
When is a haemoglobinopathy screening carried out post-natally?
at 5 days
What is the post natal haemoglobinopathy screening test?
heel prick test:
- analysis of dried blood spot
- multiple conditions tested for
- goal is early detection of sickle cell disease
State the haematological changes in pregnancy
- plasma volume expands by 50%
- red cell mass expands by 25%
- haemodilution occurs –> this means there is a fall in haemoglobin as the plasma volume expands faster than the red cell mass
- the MCV increases
- folic acid requirements increase
- leukocytosis (mainly a neutrophilia
What is the most common cause of anaemia in pregnancy?
iron deficiency
What happens to your platelet count during pregnancy?
- gestational thrombocytopenia
- platelet count drops in some women toward the end of pregnancy
What is the coagulation state in pregnancy?
- pregnancy is a pro-thrombotic state
- evidence of platelet activation
- reduction in anticoagulants and fibrinolysis
- rise in thrombin generation
Which coagulation factors are increased in pregnancy?
- plasma fibrinogen and FVII
- FV, VIII, X, XII
- big increase in vWF
erythrocyte production is controlled by what?
erythropoietin produced in kidneys
What is the function of the globin chain in haemoglobin
- protects haem from oxidation
- renders the molecule soluble
- permits variation in oxygen affinity
Explain the genetic control of an adult globin chain
- alpha chains produced on chromosome 16
- beta or gamma chains produced on chromosome 11
- forms Hb-A (adult haemaglobin)
Explain the genetic control of an foetal globin chain
- alpha chains produced on chromosome 16
- delta chains produced on chromosome 11 produce Hb-F
What is a haemaglobinopathy?
changes in globin genes or their expression leads to disease
What is a thalassaemia?
- alpha or beta
- change in globin gene expression leads to reduced rate of synthesis of normal globin chains
- pathology is due to imbalance of alpha and beta chain production
Explain structural Hb variants
- usually a single base substitution in globin gene
- altered structure and function
- HbS (sickle), C, D, E
What is the relationship between worldwide distribution of haemoglobin disorders and falciparum malaria?
suspected that the mutations persisted because they offer a survival advantage as the different red cell membrane in haemaglobin disorders results in resistance to malarial attack
How do we diagnose a haemaglobinopathy?
- FBC
- haemaglobin electrophoresis
- isoelectric focusing
- high performance liquid chromatography (HPLC)
specialist tests:
- heat stability, isopropanol
- oxygen dissociation curve
- DNA analysis
- mass spectrometry
When is the sickle cell trait a problem?
extreme hypoxia/ dehydration e.g bad anaesthesia or flying unpressurised military aircraft
Why are sickle cells so called?
Hb-S polymerises to form long fibrils which distort the red cell membrane and produce the classical sickle shape
Why do people with sickle cell disease have haemolytic anaemia?
the sickled red cells have a short life span in the blood so it requires a massive increase in red cell turnover to maintain haemoglobin
What is haemolytic anaemia?
a disorder in which red blood cells are destroyed faster than they are made
In sickle cell disease, what will you expect to see on:
- Blood count
- Blood film
- Hb electrophoresis
- anaemia
- visible sickle cells and hyposplenism
- Hb-S > 95%, Hb-A 0%
How might a patient with sickle cell disease present?
- usually 3-6 months old
- may present with jaundice, physically enlarged spleen until hyposplenism in the first decade
What are the acute complications of sickle cell disease?
- vaso-occlusive crisis –> hands and feet pain (dactylitis), chest syndrome, abdominal pain, bone infarction, priapism (painful erection)
- septicaemia due to underactive spleen
- aplastic crisis
- sequestration crisis - rapid pooling of red cells and enlargement of organ
What are the chronic complications of sickle cell disease?
- hyposplenism: due to infarction and atrophy of spleen
- renal disease
- avascular necrosis
- chronic renal failure/ dialysis
When should you transfuse patients with sickle cell?
in acute chest crisis, acute stroke, pre-operative and splenic sequestration
What is the main medical therapy for sickle cell?
hydroxycarbamide
- increases % of HbF in blood
- acts as an anti-inflammatory
What are the most common single gene disorders?
thalassaemia
What are the different types of thalassaemias?
• Divided into a, B, δβ , and γδβ according to which globin chain is reduced
What is the pathology of B-thalassaemia?
- reduced rate of production of beta globin chains
- pathology caused by excess alpha chains
What will a blood picture look like from a patient with B-thalassaemia?
- resembles iron deficiency
- small, pale red cells
- MCV reduced
What are the medical complications of thalassaemia intermedia?
- pulmonary hypertension
- extra medullary haematopoiesis
- bone changes and osteoporosis
- endocrine and fertility
- leg ulcers
What are the signs and symptoms of B-thalassaemia major?
- very severe anaemia
- short stature and distorted limb growth due to premature closure of epiphyses in long bones
- child will be pale and failure to thrive
- enlarged liver and spleen
Explain the pathology of B-thalassaemia major
- anaemia arises because there is alpha chain excess -this causes ineffective erythropoiesis (red cells die in marrow)
- so there is a shortened red cell lifespan (haemolysis)
What does a thalassaemic face look like?
- maxillary hyperthrophy
- abnormal dentition
- frontal bossing due to expanded bone marrow
What is an “hair on end” skull
- in X-ray of skull of thalassaemic patients
- due to widening of diploic cavities by marrow expansion
Why do we use a transfusion to treat B-thalassaemia major?
- to maintain mean Hb 120g/l
- suppresses marrow red cell production and prevents skeletal deformity and liver/spleen enlargement
What are the complications of transfusion?
- transmission of infection
- iron overload
- allo-immunisation
- formation of allo antibodies that make it harder to cross-match blood and infection
What is the biggest cause of death in patients with thalassaemia?
heart failure
How is iron overload prevented in thalassaemic patients?
- iron chelation therapy
- desferrioxamine
In antenatal screening for haemoglobin disorders, what are the options if antenatal test is positive?
- pre-implantation diagnostic testing
- choriovillus biopsy
- termination
How do healthy neonates and children differ haematologically from adults?
- neutrophils are increased in babies
- eosinophils and basophils do not change much in quantity
- you have the adequate number of platelets in a baby at 20 weeks
When are blood cells first made
day 18 in the yolk sac
What are the acquired causes of anaemia in childhood?
- physiological
- infection
- tumours
- trauma
- iatrogenic
- any systems
What is the most common cause of anaemia in children?
iron deficiency
