Division of Laboratory Medicine Flashcards
1
Q
What are normal are Normal Haemoglobin?
A
- Haemoglobin A - α2β2 - Major haemoglobin in adults
- Haemoglobin A2 - α2δ2 - Minor haemoglobin in adults
- Haemoglobin F - α2γ2 - Major haemoglobin in foetal life
2
Q
What are Haemoglobinopathies?
A
- Haemoglobin variants: Alteration in the globin protein structure
- Thalassaemias: Inadequate production of structurally normal globin protein.
- Thalassaemic haemoglobinopathies: Structurally abnormal haemoglobin synthesised at a reduced rate e.g. HbE.
3
Q
What are features of Haemoglobinopathies?
A
- Frequency of different haemoglobinopathies varies in different ethnic groups
- May inherit more than one haemoglobin abnormality
- Many haemoglobin mutations of no clinical significance
- Severe morbidity and mortality in sickle cell disease and beta thalassaemia major
- Carriers usually asymptomatic.
4
Q
What are features Sickle Cell Disease?
A
- Sickle haemoglobin (HbS). Occurs mainly in people of African origin
- Valine replaces glutamic acid at sixth amino acid in the β globin chain: α2β26Glu→Val (missense mutation)
- Deoxygenated HbS has reduced solubility leading to polymerisation
- Polymers distort red cell into crescent/ sickle shape
5
Q
What is the Pathogenesis of Sickle Cell Disease?
A
Sickling leads to:
- Shortened red cell survival
- Impaired passage of cells through capillaries leading to obstruction and tissue infarction
Increased adhesion to endothelium contributes to vascular occlusion
6
Q
What are some acute complication of Sickle Cell disease?
A
- Infections
- Anaemia
- Vaso-occlusive problems (Acute painful episodes, Stroke, Renal infarction, Dactylitis or bone infarction)
7
Q
What are Chronic Complications of Sickle Cell Disease?
A
- Avascular necrosis of bone
- Pulmonary hypertension
- Organ damage
- Blindness
- Leg ulcers
- Gall stones
- Chronic Renal Disease
8
Q
What are Benefits of Screening
A
- Early administration of prophylactic penicillin reduces incidence of pneumococcal sepsis.
- Pneumococcal vaccines increase immunity to pneumococcal infections
- Close clinical monitoring to detect acute splenic sequestration. Reduces morbidity and mortality. Pooling of blood in the spleen can lead to to hypovolaemic shock
- Parental education
9
Q
What is Newborn Screening Results?
A
- FS: Hb SS, Hb S/ β0 thalassaemia, Hb S/ HPFH
- FSA or FS: Hb S/ β+ thalassaemia
- FSC: Hb SC
- FSD: Hb S/DPunjab
- FSE: Hb S/E
- FSOArab: Hb S/OArab
- FSV: Unidentified Hb variant in combination with sickle Hb
10
Q
What are forms of β-thalassaemia?
A
- β0 mutations: absent or very low transcription of β globin gene
- β+ mutations: reduced expression of β globin gene
- β- thalassaemia major (die at 4 yrs age)
11
Q
What are symptoms of β-thalassaemia major (die at 4 yrs age)?
A
- Severe anaemia
- Dependent on blood transfusions
- Bone deformity if untreated
- Can cause gross hepatomegaly
12
Q
What are features of β-thalassaemia major?
A
- No HbA may indicate no β-chain synthesis
- HbA concentration <1.5% of total haemoglobin
- Newborn screening result: ‘F-only’
13
Q
What are conditions for newborn screening results?
A
- FC: Hb CC, C/β-thalassaemia
- FD: Hb DD, D/β-thalassaemia
- FE: Hb EE. Hb E/ β-thalassaemia also has an FE pattern but these children often become transfusion dependent so the condition is not clinically benign.
14
Q
What are conditions for newborn screening results?
A
- FAS: HbAS. This is a Sickle cell carrier/trait
- FAC: HbAC. This is a Carrier of Hb C
- FAD: HbAD. This is a Carrier of Hb DPunjab
- FAE: HbAE. This is a Carrier of Hb C
- FAOArab: HbAOArab. This is a Carrier of Hb OArab
15
Q
What are the linked programmes for Sickle cell screening?
A
- Screening laboratory should be informed of antenatal screening results
- If parents are carriers then ‘at risk’ form sent to lab.
- Antenatal screening results written on newborn screening card
