CP7-5 haemoglobinopathies & obstetric haematology Flashcards
At what stage of pregnancy is haemoglobinopathy screening done?
At about 8 weeks
What is involved in haemoglobinopathy screening?
getting family history
FBC +/- HPLC
+/- partner testing
If a pregnancy is classed as high risk for haemoglobinopathy, what further investigations can be done?
Prenatal diagnostic testing +/- termination of affected prgenancies or pre-implantation diagnostic testing in IVF
When does postnatal haemoglobinopathy screening done?
At 5 days
How is newborn screening of haemoglobinopathy done?
With a heal prick test to analyse dried spot blood
What is the goal of postnatal haemoglobinopathy testing?
For early detection of haemoglobinopathy like sickle cell disease
What changes in pregnancy can lead to physiological anaemia and macrocytosis?
Mother’s plasma volume increases by 50%
Her red blood cell mass expands by 25%
Haemodilution occurs
Mean cell volume increases physiologically
At what stage of pregnancy will the mother have maximum haemodilution?
32 weeks
What level of haemoglobin is classed as anaemic in the 1st and 3rd trimester?
<110 g/L
What level of haemoglobin is classed as anaemic in the 2nd trimester?
<105 g/L
What leukocytes increase in pregnancy?
Neutrophils
Left shift in maturation of myelocytes/metamyelocytes
When in pregnancy is thrombocytopenia usually marked?
After 20 weeks
What is the platelet count in 6.6%-11.6% of women towards the end of pregnancy?
<150 x 10^9 per L
What is the usual platelet count in pregnancy?
> 70 x 10^9 per L
What are some pathological causes of thrombocytopenia in pregnant women that are NOT related to the pregnancy?
Production failure in the bone marrow
Viral infection like HIV or EBV
Sepsis
Type 2B vWD
Hypersplenism
What are some pathological causes of thrombocytopenia in pregnant women that ARE pregnancy associated?
Severe folate deficiency
Pre-eclampsia
HELLP syndrome
AFLP
What evidence is there that pregnancy is a pro-thrombotic state?
Evidence of platelet activation
Increase in procoagulant factors
Reduction in natural anticoagulants
Reduction in fibrinolysis
Increased markers of thrombin generation
Increased levels of coagulation factors
At what point do changes in coagulation due to pregnancy revert to normal?
6-8 weeks post partum
What are the characteristics of normal erythrocytes?
Bi-concave discs
No nucleus
Transports O2 and CO2
Production is controlled by erythropoietin released by the kidneys in response to tissue O2 conc
What is haemoglobin?
A tetramer of globin chains (2x alpha and 2x non-alpha)which are each non-covalently bonded to a Haem
What are the three types of haemoglobin?
Hb-A
Hb-F
Hb-A2
What globin chains make up Hb-A?
2x alpha
2x beta
What globin chains make up Hb-F?
2x alpha
2x gamma
What globin chains make up Hb-A2?
2x alpha
2x delta
What is the advantage of haemoglobin being a tetramer of globins?
Globins protect the haem from oxidation
Makes the molecules soluble
Allows for variation in oxygen affinity
What haemoglobin is found in a foetus?
Hb-F
What haemoglobin is found in adults? In what perctenages?
Hb-A = >95%
Hb-A2 = <3.5%
Hb-F = <1%
What chromosome codes for the alpha globins for haemoglobin?
Chromosome 16
What chromosome codes for the gamma , delta and beta globins in haemoglobin?
Chromosome 11
At what week of development does haemoglobin production move to the liver and spleen?
10-12 weeks
In later inter uterine life, where is haemoglobin produced by the foetus?
In the bone marrow and liver
What haemoglobin is produced by the bone marrow?
Hb-A
What are some Hb structural variants that can be produced in people with haemoglobinopathy?
Hb S - aka sickle cell
Hb C
Hb D
Hb E
What usually causes structural variations of Hb?
A single base substitution in a globin gene leading to altered structure/function
What causes thalassaemia (alpha and beta)?
- Changes in globin gene expression lead to reduced rate of normal globin chain synthesis.
- This causes an inbalance of alpha and beta chain production resulting in free globins chains
- Free globin chains damage red cell membranes
What inheritance pattern is seen in haemoglobinopathy?
Autosomal recessive
What is the theory as to why haemoglobinopathy disorders developed? How does this reflect on the worldwide distribution of haemoglobin disorders?
Having the variation gave a survival advantage against malaria thus there is a high distribution of haemoglobin disorders across the tropics where malaria is more prevalent
What key tests are used in diagnosing haemoglobinopathies?
From testing FBC
Blood films
Hb electrophoresis
Isoelectric focusing
High performance liquid chromatography (HPLC)
What are further/extra investigations/ specialist tests that can be done into haemoglobinopathies?
Heat stability tests with isopropanol
Looking at O2 dissociation curves
DNA analysis
Mass spectrometry
Kleihaur testing
Supravital staining
Sickle solubility
What will investigations into a patient with heterozygous sickle cell trait look like?
Normal blood count - no anaemia
Hb electrophoresis will show presence of Hb-S (~45%) and Hb-A (~55%)
How does heterozygous sickle cell trait affect a patient?
Will have no problems except if become extremely hypoxic or dehydrated
