Sickle cell Anaemia

Question 1

what causes SCD

Answer 1

thymine is swapped for adenine (codon= GTG); also valine is subbed for glutamine at position 6 and causes a reduction in the ablity of cell to carry O2

Question 2

explain the inheritance of SCD

Answer 2

Inherited as an autosomal recessive mutation of the gene that produces the ß-globin subunit of haemoglobin.

both parents have to have an SC trait
> 1/4 chance of a child with sickle cell disease or without disease and 1/2 carrier

Question 3

pathophysiology of SCD

Answer 3

Deoxygenation– HbS loses solubility so polymerised into long chains
> Distorts red cells into a sickle shape

Vaso-occlusion occurs which obstructs smaller vessels and causes infarction Initially reversible- 02 causes cell shape to return. After many cycles irreversible

Question 4

pathophysiological obstruction of SSD

Answer 4

high adhesion molecules on the surface

Bind to vascular endothelium- narrow vessel lumen

‘Sticky’ RBC- adhere to endothelium cells= thrombosis

Haemolytic anaemia as sickle cells are removed from circulation.

Hb AS – Sickle Cell Trait – carrier state

Hb SS – Sickle Cell Disease

Question 5

Clinical Features SCD

Answer 5

Painful vaso-occlusive crisis
Visceral sequestration crisis
Aplastic crisis
Haemolytic crisis

Question 6

explain Painful vaso-occlusive crisis

Answer 6

Irreversibly sickled cells cause blockage of blood vessels
Tissues starved of 02 leads to ischemia occurring in the spleen, bones & lungs.

In 7% of all patients it occurs in the brain causing stroke

`Hand foot syndrome’ in young children(middle finger doesn’t grow tall enough

Treatment: Analgesics (even morphine) and hydration.

Question 7

explain the Visceral Sequestration Crisis

Answer 7

Pooling of red blood cells in the liver, spleen or lungs caused by sickling, and although less common, can be fatal

Question 8

explain Aplastic Crisis

Answer 8

• often due to Parvovirus/folic acid
• deficiency- characterised by sudden
  -drop in HB levels patient needing a blood transfusion

Question 9

explain haemolytic crisis

Answer 9

elevated rate of haemolysis, fallen HB, high reticulocyte count

• Lower leg ulcers
• Liver damage
• Kidney damage

Question 10

FBC Summary

Answer 10

Microcytic anaemia
> low MCV <80fl, MCH <27pg
increased immature RBC.

> Hb usually 6.0-9.0 g/dl (SCD)

> Reactive erythrocytosis -> Increased RBC production. due to low O2 but release immature RBCs with are removed causing anaemia

> High Reticulocyte Count (>5.5x10 12/L)
- bone marrow tries to compensate for anaemia

Question 11

Normal Blood Film compared to Sickle Cell

Answer 11

Question 12

explain how High-Performance Liquid Chromatography (HPLC) works

Answer 12

1. Mixture of molecules with a net POSITIVE charge (HB) are separated in a column by their adsorption onto a NEGATIVLEY charged surface (stationary phase)
2. Eluted using a liquid of increasing cation concentration (mobile phase)
3. Different HB have a different structure= different charge
4. Some will have a longer retention time in column
5. Others will elute rapidly
6. Detected optically

Question 13

HPLC – Normal Chromatogram

Answer 13

HB variants elute from the column and are detected.
The HB retention time (from injection until the maximum point of each peak) is calculated

Question 14

HBS detection in chromatography

Answer 14

A0 IS REDUCED
Hbs is apparent

Question 15

haemoglobin electrophoresis

Answer 15

Question 16

what do HPLC and Haemoglobin Electrophoresis detect

Answer 16

> Hemoglobin S (sickle HB).This type of haemoglobin is present in sickle cell disease.
Hemoglobin C (and HBF (fetal HB))
.This type of haemoglobin does not carry oxygen well.
HbH - alpha thalassemia
Hemoglobin E.This type of haemoglobin is found in people of Southeast Asian descent.
Hemoglobin D.This type of haemoglobin is present in somesickle cell disorders.

Question 17

Laboratory Diagnosis – Sickle Solubility urgent test

Answer 17

Patients blood mixed with:
> Saponin – Haemolysis of RBC
> Sodium dithionite – reducing agent to reduce 02 tension in sample

Negative – clear solution
Positive HBS– turbid solution

↳↳↳ HBS polymerises and forms a ptt of tactoid(crystals) which refract and deflect light making the solution turbid

Question 18

what is malaria

Answer 18

Malaria is caused by Plasmodium parasites spread by bite of female mosquitos

P. falciparumis the most prevalent malaria parasite on the African continent. It is responsible for most malaria-related deaths globally.

Question 19

how does SC trait link to malaria

Answer 19

HBS gene can provide immunity to malaria

To survive within the red blood cell, the parasite has to remodel the host actin.

Evolutionary pressure has resulted in mutations in human HB that prevent this remodelling.

Being a carrier confers a selective survival advantage in countries where malaria is endemic.

Question 20

Antenatal Screening Programme (2000)

Answer 20

The screening programme, recommends that all pregnant women in England be offered screening for Thalassaemia, based on the routine full blood count indices, whilst offering screening for sickle cell and other haemoglobinopathies to all women living in high prevalence areas and to minority ethnic (high risk) women in low prevalence areas.
Areas of England where there are significant minority ethnic communities are deemed high prevalence whilst areas with few minority ethnic communities are deemed low prevalence.
A combined list of high-prevalence and low-prevalence Trusts
It is recommended that women should be offered screening by ten weeks of pregnancy to identify, as early as possible and certainly before twelve weeks of pregnancy, a couple who are at risk of producing a child with a clinically significant disease.
Once identified an at-risk woman/couple are offered the option of prenatal diagnosis and if required subsequent termination of an affected pregnancy if selected.

Question 21

what is the aim of screening

Answer 21

• Support people to make informed choices during pregnancy and before conception.
• Improve infant health through prompt identification of infected babies