Haemoglobinopathies & Obstetric Haematology Flashcards
What is meant by “antenatal”?
before birth, during or relating to pregnancy
Why may someone receive an antenatal haemoglobinopathy screening?
looking at family origin and taking a full blood count (low prevalence)
or
high performance liquid chromatography (HPLC) (high prevalence)
+/- partner testing
What are the 2 different options for antenatal haemoglobinopathy screening?
prenatal diagnostic test:
- e.g. chorionic villus biopsy & genetic diagnosis at 8-12 weeks
- +/- termination of affected pregnancies
pre-implantation diagnostic testing
When may a newborn be screening for haemoglobinopathies?
How and why is this performed?
this is performed at 5 days
it involves a heel prick test and analysis of dried blood spot
the goal is early detection of sickle cell disease, allowing for parent education and antibiotic prophylaxis
How does plasma volume and red cell mass change in pregnancy?
plasma volume in pregnancy expands by 50%
red cell mass expands by 25%
what is haemodilution and when does it occur during pregnancy?
an increase in the fluid content of the blood, leading to a lower concentration of red blood cells
it occurs during pregnancy, maximally at 32 weeks
What is the definition of anaemia during pregnancy?
What is the most common cause of this and why?
Hb < 110 g / L during 1st and 3rd trimester
Hb < 105 g / L during 2nd trimester
the most common cause is iron deficiency
pregnancy increases requirements for iron and usually results in considerable mobilisation of Fe stores
How does MCV (mean cell volume) change during pregnancy?
MCV increases physiologically in pregnancy
pregnancy also increases folic acid requirements
What is leukocytosis?
When does it tend to be seen during pregnancy?
an increase in the number of white cells in the blood
this is mainly a neutrophilia rising from the 2nd month to a preak range of around 9 - 15 in the 2nd - 3rd trimester
left shift may also be seen (myelocytes / metamyelocytes)
What is meant by “left shift”?
an increase in the number of immature leukocytes in the peripheral blood, particularly neutrophil band cells
these are immature forms of neutrophils
What is normal platelet count?
What is platelet count in gestational thrombocytopenia?
normal platelet count is > 70 x 109 / L
platelet count < 150 x 109 / L in around 10% of women towards the end of pregnancy
When does platelet count fall in gestational thrombocytopenia?
How does this affect the mother and fetus?
platelet count falls after 20 weeks and thrombocytopenia is most marked in late pregnancy
there is no pathological significance for mother or foetus and there is rapid recovery following delivery
What is meant by a “prothrombotic state”?
an abnormality of blood coagulation that increases the risk of thrombosis
What factors contribute to pregnancy being a pro-thrombotic state?
- evidence of platelet activation
- increase in many procoagulant factors
- reduction in some natural anticoagulants
- reduction in fibrinolysis
- rise in markers of thrombin generation
How do the levels of coagulation factors change in pregnancy?
- marked increase in plasma fibrinogen and factor VII
- increase in factors V, VIII, X and XII
- greater increase in vWF than factor VIII (twofold in late pregnancy)
- minimal increase in FIX and small decrease in FXI
- initial increase in FXIII followed by reduction to 50% of non-pregnant value
What is the function of normal red cells?
they are biconcave discs with no nucleus
the function is to transport oxygen bound to haemoglobin
How is production of erythrocytes controlled?
production is controlled by erythropoietin (EPO)
this is produced in the kidneys in response to tissue oxygen concentration
What is the structure of haemoglobin like?
it involves a tetramer of globin chains
each globin chain is non-covalently bound to a haem group
all normal haemoglobins have 2 alpha and 2 non-alpha chains
What are the roles of the globin chain within the haemoglobin molecule?
- protects haem from oxidation
- renders the molecule soluble
- permits variation in oxygen affinity
What chromosomes are involved in genetic control of globin chains?
genes that encode the alpha globin chains are found on chromosome 16
genes that encode the non-alpha globin chains are found on chromosome 11
multiple individual genes are expressed at each site
What is the most common form of normal adult Hb?
> 95% of people have Hb-A (2a / 2b)
3.5% of people have Hb-A2 (2a / 2d)
< 1% of people have Hb-F (2a / 2y)
What is meant by a haemoglobinopathy?
What are the 2 different types?
changes in globin genes or their expression leads to disease
can be structural Hb variants or thalassaemias (alpha or beta)
What causes a structural Hb variant?
usually a single base substitution in globin gene
this leads to an altered structure and function
e.g. HbS (sickle), C, D, E, etc.
What causes a thalassaemia?
change in globin gene expression leads to reduced rate of synthesis of normal globin chains
pathology is due to an imbalance of alpha and beta chain production
free globin chains damage the red cell membrane
In autosomal recessive inheritance, if both parents are carriers what are the chances that the children will be affected?
1 in 4 chance that child will be normal
1 in 4 chance that child will be affected
1 in 2 chance that child will be a heterozygous carrier
What are the main methods used in the diagnosis of haemoglobinopathies?
full blood count / film
- haemoglobin electrophoresis
- isoelectric focusing
- high performance liquid chromatography (HPLC)
What are less common methods that can be used in the diagnosis if haemoglobinopathies?
- heat stability, isopropanol (unstable Hbs)
- oxygen dissociation curve (p50, high affinity)
- DNA analysis (genetic counselling, prenatal diagnosis)
- mass spectrometry
- Kleihauer testing, supravital staining, sickle solubility
What is the purpose of haemoglobin electrophoresis?
it is a blood test that measures the different types of haemoglobin within red blood cells
What is meant by “sickle cell trait”?
What would the patient’s blood count be like?
the patient is heterozygous (Hb A / S)
they have one abnormal allele of the haemoglobin beta gene, but do not display severe symptoms of sickle cell disease
their blood count would be normal
What would Hb electrophoresis show in someone with sickle cell trait?
What is the clinical picture?
Hb-S - 45%
Hb-A - 55%
no problems present except when there is severe hypoxia or dehydration
What happens in sickle cell disease?
sickle Hb (Hb-S) polymerises to form long fibrils which distort the red cell membrane and produce the classical sickle shape
What may reduce polymerisation in sickle cell disease?
polymerisation is reduced if other haemoglobins are present in the red cell
e.g. Hb-F in foetus or neonate
What type of anaemia is associated with sickle cell disease?
haemolytic anaemia
the sickled red blood cells have a short lifespan in the blood
How does haemolysis - associated haemostatic activation work?
- intravascular haemolysis releases haemoglobin into plasma
- haemoglobin quenches nitric oxide and generates reactive oxygen species
- arginase I is released from red blood cells during haemolysis, and metabolises arginine, the substrate for NO synthesis
- this further impairs NO homeostasis
- depletion of NO associated with platelet activation and coagulation